Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.

PubMed

Miyahara, Yoshinori; Nagaya, Noritoshi; Kataoka, Masaharu; Yanagawa, Bobby; Tanaka, Koichi; Hao, Hiroyuki; Ishino, Kozo; Ishida, Hideyuki; Shimizu, Tatsuya; Kangawa, Kenji; Sano, Shunji; Okano, Teruo; Kitamura, Soichiro; Mori, Hidezo

2006-04-01

Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration.

Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart after ischemia-reperfusion.

PubMed

Aoyagi, Toshinori; Higa, Jason K; Aoyagi, Hiroko; Yorichika, Naaiko; Shimada, Briana K; Matsui, Takashi

2015-06-15

Diet-induced obesity deteriorates the recovery of cardiac function after ischemia-reperfusion (I/R) injury. While mechanistic target of rapamycin (mTOR) is a key mediator of energy metabolism, the effects of cardiac mTOR in ischemic injury under metabolic syndrome remains undefined. Using cardiac-specific transgenic mice overexpressing mTOR (mTOR-Tg mice), we studied the effect of mTOR on cardiac function in both ex vivo and in vivo models of I/R injury in high-fat diet (HFD)-induced obese mice. mTOR-Tg and wild-type (WT) mice were fed a HFD (60% fat by calories) for 12 wk. Glucose intolerance and insulin resistance induced by the HFD were comparable between WT HFD-fed and mTOR-Tg HFD-fed mice. Functional recovery after I/R in the ex vivo Langendorff perfusion model was significantly lower in HFD-fed mice than normal chow diet-fed mice. mTOR-Tg mice demonstrated better cardiac function recovery and had less of the necrotic markers creatine kinase and lactate dehydrogenase in both feeding conditions. Additionally, mTOR overexpression suppressed expression of proinflammatory cytokines, including IL-6 and TNF-α, in both feeding conditions after I/R injury. In vivo I/R models showed that at 1 wk after I/R, HFD-fed mice exhibited worse cardiac function and larger myocardial scarring along myofibers compared with normal chow diet-fed mice. In both feeding conditions, mTOR overexpression preserved cardiac function and prevented myocardial scarring. These findings suggest that cardiac mTOR overexpression is sufficient to prevent the detrimental effects of diet-induced obesity on the heart after I/R, by reducing cardiac dysfunction and myocardial scarring. Copyright © 2015 the American Physiological Society.

Myocardial scar segmentation from magnetic resonance images using convolutional neural network

NASA Astrophysics Data System (ADS)

Zabihollahy, Fatemeh; White, James A.; Ukwatta, Eranga

2018-02-01

Accurate segmentation of the myocardial fibrosis or scar may provide important advancements for the prediction and management of malignant ventricular arrhythmias in patients with cardiovascular disease. In this paper, we propose a semi-automated method for segmentation of myocardial scar from late gadolinium enhancement magnetic resonance image (LGE-MRI) using a convolutional neural network (CNN). In contrast to image intensitybased methods, CNN-based algorithms have the potential to improve the accuracy of scar segmentation through the creation of high-level features from a combination of convolutional, detection and pooling layers. Our developed algorithm was trained using 2,336,703 image patches extracted from 420 slices of five 3D LGE-MR datasets, then validated on 2,204,178 patches from a testing dataset of seven 3D LGE-MR images including 624 slices, all obtained from patients with chronic myocardial infarction. For evaluation of the algorithm, we compared the algorithmgenerated segmentations to manual delineations by experts. Our CNN-based method reported an average Dice similarity coefficient (DSC), precision, and recall of 94.50 +/- 3.62%, 96.08 +/- 3.10%, and 93.96 +/- 3.75% as the accuracy of segmentation, respectively. As compared to several intensity threshold-based methods for scar segmentation, the results of our developed method have a greater agreement with manual expert segmentation.

3D image fusion of whole-heart dynamic cardiac MR perfusion and late gadolinium enhancement: Intuitive delineation of myocardial hypoperfusion and scar.

PubMed

von Spiczak, Jochen; Mannil, Manoj; Kozerke, Sebastian; Alkadhi, Hatem; Manka, Robert

2018-03-30

Since patients with myocardial hypoperfusion due to coronary artery disease (CAD) with preserved viability are known to benefit from revascularization, accurate differentiation of hypoperfusion from scar is desirable. To develop a framework for 3D fusion of whole-heart dynamic cardiac MR perfusion and late gadolinium enhancement (LGE) to delineate stress-induced myocardial hypoperfusion and scar. Prospective feasibility study. Sixteen patients (61 ± 14 years, two females) with known/suspected CAD. 1.5T (nine patients); 3.0T (seven patients); whole-heart dynamic 3D cardiac MR perfusion (3D-PERF, under adenosine stress); 3D LGE inversion recovery sequences (3D-SCAR). A software framework was developed for 3D fusion of 3D-PERF and 3D-SCAR. Computation steps included: 1) segmentation of the left ventricle in 3D-PERF and 3D-SCAR; 2) semiautomatic thresholding of perfusion/scar data; 3) automatic calculation of ischemic/scar burden (ie, pathologic relative to total myocardium); 4) projection of perfusion/scar values onto artificial template of the left ventricle; 5) semiautomatic coregistration to an exemplary heart contour easing 3D orientation; and 6) 3D rendering of the combined datasets using automatically defined color tables. All tasks were performed by two independent, blinded readers (J.S. and R.M.). Intraclass correlation coefficients (ICC) for determining interreader agreement. Image acquisition, postprocessing, and 3D fusion were feasible in all cases. In all, 10/16 patients showed stress-induced hypoperfusion in 3D-PERF; 8/16 patients showed LGE in 3D-SCAR. For 3D-PERF, semiautomatic thresholding was possible in all patients. For 3D-SCAR, automatic thresholding was feasible where applicable. Average ischemic burden was 11 ± 7% (J.S.) and 12 ± 7% (R.M.). Average scar burden was 8 ± 5% (J.S.) and 7 ± 4% (R.M.). Interreader agreement was excellent (ICC for 3D-PERF = 0.993, for 3D-SCAR = 0.99). 3D fusion of 3D-PERF and 3D-SCAR facilitates intuitive delineation of stress-induced myocardial hypoperfusion and scar. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Electrocardiographic Impact of Myocardial Diffuse Fibrosis and Scar: MESA (Multi-Ethnic Study of Atherosclerosis)

PubMed Central

Inoue, Yuko Y.; Ambale-Venkatesh, Bharath; Mewton, Nathan; Volpe, Gustavo J.; Ohyama, Yoshiaki; Sharma, Ravi K.; Wu, Colin O.; Liu, Chia-Ying; Bluemke, David A.; Soliman, Elsayed Z.; Lima, João A. C.

2017-01-01

Purpose To examine the associations of myocardial diffuse fibrosis and scar with surface electrocardiographic (ECG) parameters in individuals free of prior coronary heart disease in four different ethnicities. Materials and Methods This prospective cross-sectional study was approved by the institutional review boards, and all participants gave informed consent. A total of 1669 participants in the Multi-Ethnic Study of Atherosclerosis, or MESA, who were free of prior myocardial infarction underwent both ECG and cardiac magnetic resonance imaging. In individuals without a late gadolinium enhancement–defined myocardial scar (n = 1131), T1 mapping was used to assess left ventricular (LV) interstitial diffuse fibrosis. The associations of LV diffuse fibrosis or myocardial scar with ECG parameters (QRS voltage, QRS duration, and corrected QT interval [QTc]) were evaluated by using multivariable regression analyses adjusted for demographic data, risk factors for scar, LV end-diastolic volume, and LV mass. Results The mean age of the 1669 participants was 67.4 years ± 8.7 (standard deviation); 49.8% were women. Lower postcontrast T1 time at 12 minutes was significantly associated with lower QRS Sokolow-Lyon voltage (β = 15.1 µV/10 msec, P = .004), lower QRS Cornell voltage (β = 9.2 µV/10 msec, P = .031), and shorter QRS duration (β = 0.16 msec/10 msec, P = .049). Greater extracellular volume (ECV) fraction was also significantly associated with lower QRS Sokolow-Lyon voltage (β = −35.2 µV/1% ECV increase, P < .001) and Cornell voltage (β = −23.7 µV/1% ECV increase, P < .001), independent of LV structural indexes. In contrast, the presence of LV scar (n = 106) was associated with longer QTc (β = 4.3 msec, P = .031). Conclusion In older adults without prior coronary heart disease, underlying greater LV diffuse fibrosis is associated with lower QRS voltage and shorter QRS duration at surface ECG, whereas clinically unrecognized myocardial scar is associated with a longer QT interval. © RSNA, 2016 Online supplemental material is available for this article. PMID:27740904

Making Better Scar: Emerging Approaches for Modifying Mechanical and Electrical Properties Following Infarction and Ablation

PubMed Central

Holmes, Jeffrey W.; Laksman, Zachary; Gepstein, Lior

2015-01-01

Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function – maintaining integrity of the heart wall against enormous mechanical forces – but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches. PMID:26615948

Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease.

PubMed

Deva, Djeven Parameshvara; Hanneman, Kate; Li, Qin; Ng, Ming Yen; Wasim, Syed; Morel, Chantal; Iwanochko, Robert M; Thavendiranathan, Paaladinesh; Crean, Andrew Michael

2016-03-31

Although it is known that Anderson-Fabry Disease (AFD) can mimic the morphologic manifestations of hypertrophic cardiomyopathy (HCM) on echocardiography, there is a lack of cardiovascular magnetic resonance (CMR) literature on this. There is limited information in the published literature on the distribution of myocardial fibrosis in patients with AFD, with scar reported principally in the basal inferolateral midwall. All patients with confirmed AFD undergoing CMR at our center were included. Left ventricular (LV) volumes, wall thicknesses and scar were analyzed offline. Patients were categorized into 4 groups: (1) no wall thickening; (2) concentric hypertrophy; (3) asymmetric septal hypertrophy (ASH); and (4) apical hypertrophy. Charts were reviewed for clinical information. Thirty-nine patients were included (20 males [51%], median age 45.2 years [range 22.3-64.4]). Almost half (17/39) had concentric wall thickening. Almost half (17/39) had pathologic LV scar; three quarters of these (13/17) had typical inferolateral midwall scar. A quarter (9/39) had both concentric wall thickening and typical inferolateral scar. A subgroup with ASH and apical hypertrophy (n = 5) had greater maximum wall thickness, total LV scar, apical scar and mid-ventricular scar than those with concentric hypertrophy (n = 17, p < 0.05). Patients with elevated LVMI had more overall arrhythmia (p = 0.007) more ventricular arrhythmia (p = 0.007) and sustained ventricular tachycardia (p = 0.008). Concentric thickening and inferolateral mid-myocardial scar are the most common manifestations of AFD, but the spectrum includes cases morphologically identical to apical and ASH subtypes of HCM and these have more apical and mid-ventricular LV scar. Significant LVH is associated with ventricular arrhythmia.

Assessment of myocardial viability: comparison of echocardiography versus cardiac magnetic resonance imaging in the current era.

PubMed

Tomlinson, David R; Becher, Harald; Selvanayagam, Joseph B

2008-06-01

Detecting viable myocardium, whether hibernating or stunned, is of clinical significance in patients with coronary artery disease and left ventricular dysfunction. Echocardiographic assessments of myocardial thickening and endocardial excursion during dobutamine infusion provide a highly specific marker for myocardial viability, but with relatively less sensitivity. The additional modalities of myocardial contrast echocardiography and tissue Doppler have recently been proposed to provide further, quantitative measures of myocardial viability assessment. Cardiac magnetic resonance (CMR) has become popular for the assessment of myocardial viability as it can assess cardiac function, volumes, myocardial scar, and perfusion with high-spatial resolution. Both 'delayed enhancement' CMR and dobutamine stress CMR have important roles in the assessment of patients with ischaemic cardiomyopathy. This article reviews the recent advances in both echocardiography and CMR for the clinical assessment of myocardial viability. It attempts to provide a pragmatic approach toward the patient-specific assessment of this important clinical problem.

Using the laws of thermodynamics to understand how matrix metalloproteinases coordinate the myocardial response to injury.

PubMed

Iyer, Rugmani Padmanabhan; Jung, Mira; Lindsey, Merry L

Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of molecular, cellular, and functional alterations that are both part of the wound healing response to form a scar in the infarct region and the consequence of that response. Using the laws of thermodynamics as an analogy, we present here three laws for categorizing the post-MI LV remodeling process. The first law is that the LV will attempt to maintain equilibrium and compensate as a way to maximize function, the second law is that remodeling is progressive and unidirectional, and the third law is that the final goal is (ideally, but not always achievable) a stable, equilibrated scar. This comparison helps to define the boundaries of the system, whether it be the infarct zone, the LV, the heart, or the entire body. This review provides an overview for those not directly in the field and establishes a framework to help prioritize future research directions.

Using the laws of thermodynamics to understand how matrix metalloproteinases coordinate the myocardial response to injury

PubMed Central

Iyer, Rugmani Padmanabhan; Jung, Mira; Lindsey, Merry L

2016-01-01

Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of molecular, cellular, and functional alterations that are both part of the wound healing response to form a scar in the infarct region and the consequence of that response. Using the laws of thermodynamics as an analogy, we present here three laws for categorizing the post-MI LV remodeling process. The first law is that the LV will attempt to maintain equilibrium and compensate as a way to maximize function, the second law is that remodeling is progressive and unidirectional, and the third law is that the final goal is (ideally, but not always achievable) a stable, equilibrated scar. This comparison helps to define the boundaries of the system, whether it be the infarct zone, the LV, the heart, or the entire body. This review provides an overview for those not directly in the field and establishes a framework to help prioritize future research directions. PMID:27376092

Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okura, Hanayuki; Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047; Saga, Ayami

Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion ofmore » the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of human specific alpha-cardiac actin. Human alpha cardiac actin-positive cells also expressed cardiac nuclear factors; nkx2.5 and GATA-4. Our results suggest that intracoronary artery transplantation of hCLCs is a potentially effective therapeutic strategy for future cardiac tissue regeneration.« less

Selective inhibition of receptor activator of NF-κB ligand (RANKL) in hematopoietic cells improves outcome after experimental myocardial infarction.

PubMed

Slavic, Svetlana; Andrukhova, Olena; Ford, Kristopher; Handschuh, Stephan; Latic, Nejla; Reichart, Ursula; Sasgary, Soleman; Bergow, Claudia; Hofbauer, Lorenz C; Kostenuik, Paul J; Erben, Reinhold G

2018-05-08

The RANK (receptor activator of nuclear factor κB)/RANKL (RANK ligand)/OPG (osteoprotegerin) axis is activated after myocardial infarction (MI), but its pathophysiological role is not well understood. Here, we investigated how global and cell compartment-selective inhibition of RANKL affects cardiac function and remodeling after MI in mice. Global RANKL inhibition was achieved by treatment of human RANKL knock-in (huRANKL-KI) mice with the monoclonal antibody AMG161. huRANKL-KI mice express a chimeric RANKL protein wherein part of the RANKL molecule is humanized. AMG161 inhibits human and chimeric but not murine RANKL. To dissect the pathophysiological role of RANKL derived from hematopoietic and mesenchymal cells, we selectively exchanged the hematopoietic cell compartment by lethal irradiation and across-genotype bone marrow transplantation between wild-type and huRANKL-KI mice, exploiting the specificity of AMG161. After permanent coronary artery ligation, mice were injected with AMG161 or an isotype control antibody over 4 weeks post-MI. MI increased RANKL expression mainly in cardiomyocytes and scar-infiltrating cells 4 weeks after MI. Only inhibition of RANKL derived from hematopoietic cellular sources, but not global or mesenchymal RANKL inhibition, improved post-infarct survival and cardiac function. Mechanistically, hematopoietic RANKL inhibition reduced expression of the pro-inflammatory cytokine IL-1ß in the cardiac cellular infiltrate. In conclusion, inhibition of RANKL derived from hematopoietic cellular sources is beneficial to maintain post-ischemic cardiac function by reduction of pro-inflammatory cytokine production. Experimental myocardial infarction (MI) augments cardiac RANKL expression in mice. RANKL expression is increased in cardiomyocytes and scar-infiltrating cells after MI. Global or mesenchymal cell RANKL inhibition has no influence on cardiac function after MI. Inhibition of RANKL derived from hematopoietic cells improves heart function post-MI. Hematopoietic RANKL inhibition reduces pro-inflammatory cytokines in scar-infiltrating cells.

Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation.

PubMed

Holmes, Jeffrey W; Laksman, Zachary; Gepstein, Lior

2016-01-01

Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function - maintaining integrity of the heart wall against enormous mechanical forces - but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modifying the mechanics of healing infarcts: Is better the enemy of good?

PubMed

Clarke, Samantha A; Richardson, William J; Holmes, Jeffrey W

2016-04-01

Myocardial infarction (MI) is a major source of morbidity and mortality worldwide, with over 7 million people suffering infarctions each year. Heart muscle damaged during MI is replaced by a collagenous scar over a period of several weeks, and the mechanical properties of that scar tissue are a key determinant of serious post-MI complications such as infarct rupture, depression of heart function, and progression to heart failure. Thus, there is increasing interest in developing therapies that modify the structure and mechanics of healing infarct scar. Yet most prior attempts at therapeutic scar modification have failed, some catastrophically. This article reviews available information about the mechanics of healing infarct scar and the functional impact of scar mechanical properties, and attempts to infer principles that can better guide future attempts to modify scar. One important conclusion is that collagen structure, mechanics, and remodeling of healing infarct scar vary so widely among experimental models that any novel therapy should be tested across a range of species, infarct locations, and reperfusion protocols. Another lesson from past work is that the biology and mechanics of healing infarcts are sufficiently complex that the effects of interventions are often counterintuitive; for example, increasing infarct stiffness has little effect on heart function, and inhibition of matrix metalloproteases (MMPs) has little effect on scar collagen content. Computational models can help explain such counterintuitive results, and are becoming an increasingly important tool for integrating known information to better identify promising therapies and design experiments to test them. Moving forward, potentially exciting new opportunities for therapeutic modification of infarct mechanics include modulating anisotropy and promoting scar compaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Loss of the LIM-only protein Fhl2 impairs inflammatory reaction and scar formation after cardiac ischemia leading to better hemodynamic performance.

PubMed

Goltz, Diane; Hittetiya, Kanishka; Gevensleben, Heidrun; Kirfel, Jutta; Diehl, Linda; Meyer, Rainer; Büttner, Reinhard

2016-04-15

The pathogenesis of myocardial ischemia-reperfusion injury (MI/R) involves an inflammatory response. Since the four-and-a-half LIM domain-containing protein 2 (Fhl2) has been observed to modulate immune cell migration, we aimed to study the consequences of Fhl2(-/-) under MI/R with respect to immune reaction, scar formation, and hemodynamic performance. In a closed chest model of 1h MI/R, immune cell invasion of phagocytic monocytes was characterized by flow cytometry and immunohistochemistry. In addition, infarct size was assessed by triphenyltetrazolium chloride/Masson trichrome staining 24h/21days after reperfusion and a set of hemodynamic parameters was recorded by catheterisation in Fhl2(-/-) mice and controls. While flow cytometry did not reveal differences in myocardial CD45(high) immune cell infiltrate, histological analysis showed that infiltrating immune cells in Fhl2(-/-) animals were preferentially located in the perivascular area, whereas in wild type, immune cells were well dispersed within the area at risk. After 24h and 21days of reperfusion, infarct size was significantly reduced in Fhl2(-/-) compared to WT animals. In addition, hemodynamic performance was better in Fhl2(-/-) mice, compared to WT mice up to day 21 of reperfusion. The loss of Fhl2 leads to an altered immune response to myocardial ischemia, which results in smaller infarcts and better hemodynamic performance up to 21days after myocardial ischemia reperfusion. Immune cell invasion plays a pivotal role in the context of MI/R. Fhl2 significantly influences immune cell function and immune cell interaction with injured cardiac tissue leading to altered scar composition. Copyright © 2016 Elsevier Inc. All rights reserved.

Pivotal role of phospholipase D1 in tumor necrosis factor-α-mediated inflammation and scar formation after myocardial ischemia and reperfusion in mice.

PubMed

Schönberger, Tanja; Jürgens, Tobias; Müller, Julia; Armbruster, Nicole; Niermann, Christina; Gorressen, Simone; Sommer, Jan; Tian, Huasong; di Paolo, Gilbert; Scheller, Jürgen; Fischer, Jens W; Gawaz, Meinrad; Elvers, Margitta

2014-09-01

Myocardial inflammation is critical for ventricular remodeling after ischemia. Phospholipid mediators play an important role in inflammatory processes. In the plasma membrane they are degraded by phospholipase D1 (PLD1). PLD1 was shown to be critically involved in ischemic cardiovascular events. Moreover, PLD1 is coupled to tumor necrosis factor-α signaling and inflammatory processes. However, the impact of PLD1 in inflammatory cardiovascular disease remains elusive. Here, we analyzed the impact of PLD1 in tumor necrosis factor-α-mediated activation of monocytes after myocardial ischemia and reperfusion using a mouse model of myocardial infarction. PLD1 expression was highly up-regulated in the myocardium after ischemia/reperfusion. Genetic ablation of PLD1 led to defective cell adhesion and migration of inflammatory cells into the infarct border zone 24 hours after ischemia/reperfusion injury, likely owing to reduced tumor necrosis factor-α expression and release, followed by impaired nuclear factor-κB activation and interleukin-1 release. Moreover, PLD1 was found to be important for transforming growth factor-β secretion and smooth muscle α-actin expression of cardiac fibroblasts because myofibroblast differentiation and interstitial collagen deposition were altered in Pld1(-/-) mice. Consequently, infarct size was increased and left ventricular function was impaired 28 days after myocardial infarction in Pld1(-/-) mice. Our results indicate that PLD1 is crucial for tumor necrosis factor-α-mediated inflammation and transforming growth factor-β-mediated collagen scar formation, thereby augmenting cardiac left ventricular function after ischemia/reperfusion. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Inhomogeneity of collagen organization within the fibrotic scar after myocardial infarction: results in a swine model and in human samples.

PubMed

Hervas, Arantxa; Ruiz-Sauri, Amparo; de Dios, Elena; Forteza, Maria Jose; Minana, Gema; Nunez, Julio; Gomez, Cristina; Bonanad, Clara; Perez-Sole, Nerea; Gavara, Jose; Chorro, Francisco Javier; Bodi, Vicente

2016-01-01

We aimed to characterize the organization of collagen within a fibrotic scar in swine and human samples from patients with chronic infarctions. Swine were subjected to occlusion of the left anterior descending artery followed by reperfusion 1 week (acute myocardial infarction group) or 1 month (chronic myocardial infarction group) after infarction. The organization of the collagen fibers (Fast Fourier Transform of samples after picrosirius staining; higher values indicate more disorganization) was studied in 100 swine and 95 human samples. No differences in collagen organization were found between the acute and chronic groups in the core area of the scar in the experimental model. In the chronic group, the endocardium [0.90 (0.84-0.94); median (interquartile range)], epicardium [0.84 (0.79-0.91)] and peripheral area [0.73 (0.63-0.83)] displayed a much more disorganized pattern than the core area of the fibrotic scar [0.56 (0.45-0.64)]. Similarly, in human samples, the collagen fibers were more disorganized in all of the outer areas than in the core of the fibrotic scar (P < 0.0001). Both in a highly controlled experimental model and in patient samples, collagen fibers exhibited an organized pattern in the core of the infarction, whereas the outer areas displayed a high level of inhomogeneity. This finding contributes pathophysiological information regarding the healing process and may lead to a clearer understanding of the genesis and invasive treatment of arrhythmias after acute myocardial infarction. © 2015 Anatomical Society.

Connexin43 Gene Transfer Reduces Ventricular Tachycardia Susceptibility After Myocardial Infarction

PubMed Central

Greener, Ian D.; Sasano, Tetsuo; Wan, Xiaoping; Igarashi, Tomonori; Strom, Maria; Rosenbaum, David S.; Donahue, J. Kevin

2012-01-01

Objectives The aim of this study was to evaluate the links between connexin43 (Cx43) expression, myocardial conduction velocity, and ventricular tachycardia in a model of healed myocardial infarction. Background Post-infarction ventricular arrhythmias frequently cause sudden death. Impaired myocardial conduction has previously been linked to ventricular arrhythmias. Altered connexin expression is a potential source of conduction slowing identified in healed scar border tissues. The functional effect of increasing border-zone Cx43 has not been previously evaluated. Methods Twenty-five Yorkshire pigs underwent anterior infarction by transient left anterior descending coronary artery occlusion, followed by weekly testing for arrhythmia inducibility. Twenty animals with reproducibly inducible sustained monomorphic ventricular tachycardia were randomized 2:1:1 to receive AdCx43, Adβgal, or no gene transfer. One week later, animals underwent follow-up electrophysiologic study and tissue assessment for several functional and molecular measures. Results Animals receiving AdCx43 had less electrogram fractionation and faster conduction velocity in the anterior-septal border zone. Only 40% of AdCx43 animals remained inducible for ventricular tachycardia, while 100% of controls were inducible after gene transfer. AdCx43 animals had 2-fold higher Cx43 protein levels in the anterior-septal infarct border, with similar percents of phosphorylated and intercalated disk-localized Cx43 compared with controls. Conclusions These data mechanistically link Cx43 expression to slow conduction and arrhythmia susceptibility in the healed scar border zone. Targeted manipulation of Cx43 levels improved conduction velocity and reduced ventricular tachycardia susceptibility. Cx43 gene transfer represents a novel treatment strategy for post-infarction arrhythmias. PMID:22883636

Myocardial Scar Imaging by Standard Single-Energy and Dual-Energy Late Enhancement Computed Tomography: Comparison to Pathology and Electroanatomical Map in an Experimental Chronic Infarct Porcine Model

PubMed Central

Truong, Quynh A.; Thai, Wai-ee; Wai, Bryan; Cordaro, Kevin; Cheng, Teresa; Beaudoin, Jonathan; Xiong, Guanglei; Cheung, Jim W.; Altman, Robert; Min, James K.; Singh, Jagmeet P.; Barrett, Conor D.; Danik, Stephan

2015-01-01

Background Myocardial scar is a substrate for ventricular tachycardia and sudden cardiac death. Late enhancement computed tomography (CT) imaging can detect scar, but it remains unclear whether newer late enhancement dual-energy (LE-DECT) acquisition has benefit over standard single-energy late enhancement (LE-CT). Objective We aim to compare late enhancement CT using newer LE-DECT acquisition and single-energy LE-CT acquisitions to pathology and electroanatomical map (EAM) in an experimental chronic myocardial infarction (MI) porcine study. Methods In 8 chronic MI pigs (59±5 kg), we performed dual-source CT, EAM, and pathology. For CT imaging, we performed 3 acquisitions at 10 minutes post-contrast: LE-CT 80 kV, LE-CT 100 kV, and LE-DECT with two post-processing software settings. Results Of the sequences, LE-CT 100 kV provided the best contrast-to-noise ratio (all p≤0.03) and correlation to pathology for scar (ρ=0.88). While LE-DECT overestimated scar (both p=0.02), LE-CT images did not (both p=0.08). On a segment basis (n=136), all CT sequences had high specificity (87–93%) and modest sensitivity (50–67%), with LE-CT 100 kV having the highest specificity of 93% for scar detection compared to pathology and agreement with EAM (κ 0.69). Conclusions Standard single-energy LE-CT, particularly 100kV, matched better to pathology and EAM than dual-energy LE-DECT for scar detection. Larger human trials as well as more technical-based studies that optimize varying different energies with newer hardware and software are warranted. PMID:25977115

Polypyrrole-chitosan conductive biomaterial synchronizes cardiomyocyte contraction and improves myocardial electrical impulse propagation.

PubMed

Cui, Zhi; Ni, Nathan C; Wu, Jun; Du, Guo-Qing; He, Sheng; Yau, Terrence M; Weisel, Richard D; Sung, Hsing-Wen; Li, Ren-Ke

2018-01-01

Background: The post-myocardial infarction (MI) scar interrupts electrical impulse propagation and delays regional contraction, which contributes to ventricular dysfunction. We investigated the potential of an injectable conductive biomaterial to restore scar tissue conductivity and re-establish synchronous ventricular contraction. Methods: A conductive biomaterial was generated by conjugating conductive polypyrrole (PPY) onto chitosan (CHI) backbones. Trypan blue staining of neonatal rat cardiomyocytes (CMs) cultured on biomaterials was used to evaluate the biocompatibility of the conductive biomaterials. Ca 2+ imaging was used to visualize beating CMs. A cryoablation injury rat model was used to investigate the ability of PPY:CHI to improve cardiac electrical propagation in the injured heart in vivo . Electromyography was used to evaluate conductivity of scar tissue ex vivo . Results: Cell survival and morphology were similar between cells cultured on biomaterials-coated and uncoated-control dishes. PPY:CHI established synchronous contraction of two distinct clusters of spontaneously-beating CMs. Intramyocardial PPY:CHI injection into the cryoablation-induced injured region improved electrical impulse propagation across the scarred tissue and decreased the QRS interval, whereas saline- or CHI-injected hearts continued to have delayed propagation patterns and significantly reduced conduction velocity compared to healthy controls. Ex vivo evaluation found that scar tissue from PPY:CHI-treated rat hearts had higher signal amplitude compared to those from saline- or CHI-treated rat heart tissue. Conclusions: The PPY:CHI biomaterial is electrically conductive, biocompatible and injectable. It improved synchronous contraction between physically separated beating CM clusters in vitro . Intra-myocardial injection of PPY:CHI following cardiac injury improved electrical impulse propagation of scar tissue in vivo .

Stimulation of cardiomyocyte regeneration in neonatal mice and in human myocardium with neuregulin reveals a therapeutic window

PubMed Central

Polizzotti, Brian D.; Ganapathy, Balakrishnan; Walsh, Stuart; Choudhury, Sangita; Ammanamanchi, Niyatie; Bennett, David G.; dos Remedios, Cristobal G.; Haubner, Bernhard J.; Penninger, Josef M.; Kuhn, Bernhard

2015-01-01

Background Pediatric patients with heart failure are treated with medical therapies that were developed for adult patients. These therapies have been shown to be ineffective in pediatric trials, leading to the recognition that new pediatric-specific therapies must be developed. We have previously shown that administration of the recombinant growth factor neuregulin-1 (rNRG1) stimulates heart muscle cell (cardiomyocyte) regeneration in adult mice. We hypothesized that rNRG1 administration may be more effective in the neonatal period, which could provide a new therapeutic paradigm for treating heart failure in pediatric patients. Methods We used a cryoinjury model to induce myocardial dysfunction and scar formation for evaluating the effectiveness of rNRG1-administration in neonatal mice. We evaluated the ability of rNRG1 to stimulate cardiomyocyte proliferation in intact cultured myocardium from pediatric patients. Results After cryoinjury in neonatal mice, early administration of rNRG1 from birth for 34 days improved myocardial function and reduced the prevalence of transmural scars. In contrast, late administration of rNRG1 from 4 to 34 days after cryoinjury transiently improved myocardial function. The mechanisms of early administration involved cardiomyocyte protection (38%) and proliferation (62%). rNRG1 induced cardiomyocyte proliferation in myocardium from infants with heart disease less than 6 months of age. Conclusion Our results identify a more effective time period within which to execute future clinical trials of rNRG1 for stimulating cardiomyocyte regeneration. PMID:25834111

Scar extent as a predictive factor of ventricular tachycardia cycle length after myocardial infarction: implications for implantable cardioverter-defibrillator programming optimization.

PubMed

Alexandre, Joachim; Saloux, Eric; Lebon, Alain; Dugué, Audrey Emmanuelle; Lemaitre, Adrien; Roule, Vincent; Labombarda, Fabien; Champ-Rigot, Laure; Gomes, Sophie; Pellissier, Arnaud; Scanu, Patrice; Milliez, Paul

2014-02-01

After an old myocardial infarction (MI), patients are at risk for reentrant ventricular tachycardia (VT) due to scar tissue that can be accurately identified by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Although the ability of LGE-CMR to predict sustained VT in implantable cardioverter-defibrillator (ICD) recipients has been well established, its use to predict monomorphic VT (sustained or not) cycle length (CL) and so, optimize ICD programming has never been investigated. We included retrospectively 49 consecutive patients with an old MI who had undergone LGE-CMR before ICD implantation over a 4-year period (2006-09). Patients with amiodarone used were excluded. Scar extent was assessed by measuring scar mass, percent scar, and transmural scar extent. The endpoint was the occurrence of monomorphic VT, requiring an ICD therapy or not. The endpoint occurred in 26 patients. The median follow-up duration was 31 months. Scar extent parameters were significantly correlated with the study endpoint. With univariate regression analysis, the scar mass had the highest correlation with the VT CL (R = 0.671, P = 0.0002). Receiver-operating characteristic curve showed that scar mass can predict VT CL (area under the curve = 0.977, P < 0.0001). For a cut-off value of scar mass at 17.6 g, there is 100% specificity and 94.4% sensitivity. In this observational and retrospective study, scar mass studied by LGE-CMR was specific and sensitive to predict VT CL and so could be a promising option to improve ICD post-implantation programming and decrease appropriate and inappropriate shocks. These conclusions must now be confirmed in a large and prospective study.

Development of bioartificial myocardium using stem cells and nanobiotechnology templates.

PubMed

Chachques, Juan Carlos

2010-12-29

Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The development of a bioartificial myocardium is a new challenge; in this approach, tissue-engineered procedures are associated with cell therapy. Organ decellularization for bioscaffolds fabrication is a new investigated concept. Nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/administration properties. Investigating the electrophysiological properties of bioartificial myocardium is the challenging objective of future research, associating a multielectrode network to provide electrical stimulation could improve the coupling of grafted cells and scaffolds with host cardiomyocytes. In summary, until now stem cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases. Supported by relevant scientific background, the development of myocardial tissue engineering may constitute a new avenue and hope for the treatment of myocardial diseases.

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

PubMed

Roell, Wilhelm; Klein, Alexandra M; Breitbach, Martin; Becker, Torsten S; Parikh, Ashish; Lee, Jane; Zimmermann, Katrin; Reining, Shaun; Gabris, Beth; Ottersbach, Annika; Doran, Robert; Engelbrecht, Britta; Schiffer, Miriam; Kimura, Kenichi; Freitag, Patricia; Carls, Esther; Geisen, Caroline; Duerr, Georg D; Sasse, Philipp; Welz, Armin; Pfeifer, Alexander; Salama, Guy; Kotlikoff, Michael; Fleischmann, Bernd K

2018-05-08

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 + cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

Cardiogenic Genes Expressed in Cardiac Fibroblasts Contribute to Heart Development and Repair

PubMed Central

Furtado, Milena B.; Costa, Mauro W.; Pranoto, Edward Adi; Salimova, Ekaterina; Pinto, Alex; Lam, Nicholas T.; Park, Anthony; Snider, Paige; Chandran, Anjana; Harvey, Richard P.; Boyd, Richard; Conway, Simon J.; Pearson, James; Kaye, David M.; Rosenthal, Nadia A.

2014-01-01

Rationale Cardiac fibroblasts are critical to proper heart function through multiple interactions with the myocardial compartment but appreciation of their contribution has suffered from incomplete characterization and lack of cell-specific markers. Objective To generate an unbiased comparative gene expression profile of the cardiac fibroblast pool, identify and characterize the role of key genes in cardiac fibroblast function, and determine their contribution to myocardial development and regeneration. Methods and Results High-throughput cell surface and intracellular profiling of cardiac and tail fibroblasts identified canonical MSC and a surprising number of cardiogenic genes, some expressed at higher levels than in whole heart. Whilst genetically marked fibroblasts contributed heterogeneously to interstitial but not cardiomyocyte compartments in infarcted hearts, fibroblast-restricted depletion of one highly expressed cardiogenic marker, Tbx20, caused marked myocardial dysmorphology and perturbations in scar formation upon myocardial infarction. Conclusions The surprising transcriptional identity of cardiac fibroblasts, the adoption of cardiogenic gene programs and direct contribution to cardiac development and repair provokes alternative interpretations for studies on more specialized cardiac progenitors, offering a novel perspective for reinterpreting cardiac regenerative therapies. PMID:24650916

Speckle-Tracking Layer-Specific Analysis of Myocardial Deformation and Evaluation of Scar Transmurality in Chronic Ischemic Heart Disease.

PubMed

Tarascio, Michela; Leo, Laura Anna; Klersy, Catherine; Murzilli, Romina; Moccetti, Tiziano; Faletra, Francesco Fulvio

2017-07-01

Identification of the extent of scar transmurality in chronic ischemic heart disease is important because it correlates with viability. The aim of this retrospective study was to evaluate whether layer-specific two-dimensional speckle-tracking echocardiography allows distinction of scar presence and transmurality. A total of 70 subjects, 49 with chronic ischemic cardiomyopathy and 21 healthy subjects, underwent two-dimensional speckle-tracking echocardiography and late gadolinium-enhanced cardiac magnetic resonance. Scar extent was determined as the relative amount of hyperenhancement using late gadolinium-enhanced cardiac magnetic resonance in an 18-segment model (0% hyperenhancement = normal; 1%-50% = subendocardial scar; 51%-100% = transmural scar). In the same 18-segment model, peak systolic circumferential strain and longitudinal strain were calculated separately for the endocardial and epicardial layers as well as the full-wall myocardial thickness. All strain parameters showed cutoff values (area under the curve > 0.69) that allowed the discrimination of normal versus scar segments but not of transmural versus subendocardial scars. This was true for all strain parameters analyzed, without differences in efficacy between longitudinal and circumferential strain and subendocardial, subepicardial, and full-wall-thickness strain values. Circumferential and longitudinal strain in normal segments showed transmural and basoapical gradients (greatest values at the subendocardial layer and apex). In segments with scar, transmural gradient was maintained, whereas basoapical gradient was lost because the reduction of strain values in the presence of the scar was greater at the apex. The two-dimensional speckle-tracking echocardiographic values distinguish scar presence but not transmurality; thus, they are not useful predictors of scar segment viability. It remains unclear why there is a greater strain value reduction in the presence of a scar at the apical level. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Semi-automated scar detection in delayed enhanced cardiac magnetic resonance images

NASA Astrophysics Data System (ADS)

Morisi, Rita; Donini, Bruno; Lanconelli, Nico; Rosengarden, James; Morgan, John; Harden, Stephen; Curzen, Nick

2015-06-01

Late enhancement cardiac magnetic resonance images (MRI) has the ability to precisely delineate myocardial scars. We present a semi-automated method for detecting scars in cardiac MRI. This model has the potential to improve routine clinical practice since quantification is not currently offered due to time constraints. A first segmentation step was developed for extracting the target regions for potential scar and determining pre-candidate objects. Pattern recognition methods are then applied to the segmented images in order to detect the position of the myocardial scar. The database of late gadolinium enhancement (LE) cardiac MR images consists of 111 blocks of images acquired from 63 patients at the University Hospital Southampton NHS Foundation Trust (UK). At least one scar was present for each patient, and all the scars were manually annotated by an expert. A group of images (around one third of the entire set) was used for training the system which was subsequently tested on all the remaining images. Four different classifiers were trained (Support Vector Machine (SVM), k-nearest neighbor (KNN), Bayesian and feed-forward neural network) and their performance was evaluated by using Free response Receiver Operating Characteristic (FROC) analysis. Feature selection was implemented for analyzing the importance of the various features. The segmentation method proposed allowed the region affected by the scar to be extracted correctly in 96% of the blocks of images. The SVM was shown to be the best classifier for our task, and our system reached an overall sensitivity of 80% with less than 7 false positives per patient. The method we present provides an effective tool for detection of scars on cardiac MRI. This may be of value in clinical practice by permitting routine reporting of scar quantification.

Myocardial imaging with 99mTc-Tetrofosmin: Influence of post-stress acquisition time, regional radiotracer uptake, and wall motion abnormalities on the clinical result.

PubMed

Giorgetti, Assuero; Kusch, Annette; Casagranda, Mirta; Tagliavia, Irene D'Aragona; Marzullo, Paolo

2010-04-01

We previously demonstrated that early (15', T1) post-stress myocardial imaging with Tetrofosmin could be more accurate than standard acquisitions (45', T2) in identifying coronary artery disease. To clarify this phenomenon, 120 subjects (age 61 +/- 10 years) with both T1 and T2 scans were divided into Group 1 (53/120 pts) with more ischemia at T1 vs T2 imaging (T1-T2SDS > or = 3); Group 2 (67/120 pts) with similar results (T1-T2SDS < or = 2). Myocardial areas were categorized as control nonischemic, ischemic, and scarred on the basis of perfusion/contraction properties and coronary anatomy. In each area, regional myocardial count statistic and semiquantitative wall motion/thickening values were obtained. Analysis of T1 and T2 post-stress myocardial counts demonstrated a significant Tetrofosmin wash-out rate that was higher in Group 1 control nonischemic regions (15 +/- 8% vs 13.6 +/- 9.6%, P < .02), significantly lower in Group 1 ischemic regions (7 +/- 10% vs 12.2 +/- 9.5%, P < .0001), and comparable between scarred areas of the two groups (P = NS). Delta post-stress wall thickening (T1-T2) was lower in Group 1 ischemic regions (-4.5 +/- 9.15% vs -1.90 +/- 7.0%, P < .001) and comparable in both control nonischemic and scarred areas of the two groups (P = NS). The clinical result of Tetrofosmin gated-SPECT can be influenced by the post-stress acquisition time because of ischemic-induced regional wall thickening abnormalities and the existence of a differential radiotracer myocardial wash-out.

The Role of CMR in Cardiomyopathies

PubMed Central

Kramer, Christopher M.

2015-01-01

Cardiac magnetic resonance imaging (CMR) has made major inroads in the new millenium in the diagnosis and assessment of prognosis for patients with cardiomyopathies. Imaging of left and right ventricular structure and function and tissue characterization with late gadolinium enhancement (LGE) as well as T1 and T2 mapping enable accurate diagnosis of the underlying etiology. In the setting of coronary artery disease, either transmurality of LGE or contractile reserve in response to dobutamine can assess the likelihood of recovery of function after revascularization. The presence of scar reduces the likelihood of response to medical therapy and to cardiac resynchronization therapy in heart failure. The presence and extent of LGE relate to overall cardiovascular outcome in cardiomyopathies. An emerging major role for CMR in cardiomyopathies is to identify myocardial scar for diagnostic and prognostic purposes. PMID:26033902

Wideband late gadolinium enhanced magnetic resonance imaging for imaging myocardial scar without image artefacts induced by implantable cardioverter-defibrillator: a feasibility study at 3 T

PubMed Central

Ranjan, Ravi; McGann, Christopher J.; Jeong, Eun-Kee; Hong, KyungPyo; Kholmovski, Eugene G.; Blauer, Josh; Wilson, Brent D.; Marrouche, Nassir F.; Kim, Daniel

2015-01-01

Aim Late gadolinium enhanced (LGE) magnetic resonance imaging (MRI) is a useful tool for facilitating ventricular tachycardia (VT) ablation. Unfortunately, most VT ablation candidates often have prophylactic implantable cardioverter-defibrillator (ICD) and do not undergo cardiac MRI largely due to image artefacts generated by ICD. A prior study has reported success of ‘wideband’ LGE MRI for imaging myocardial scar without image artefacts induced by ICD at 1.5T. The purpose of this study was to widen the availability of wideband LGE MRI to 3T, since it has the potential to achieve higher spatial resolution than 1.5T. Methods and results We compared the performance of standard and wideband LGE MRI pulse sequences in phantoms and canines with myocardial lesions created by radiofrequency ablation. Standard LGE MRI produced image artefacts induced by ICD and 49% accuracy in detecting 97 myocardial scars examined in this study, whereas wideband LGE MRI produced artefact-free images and 94% accuracy in detecting scars. The mean image quality score (1 = nondiagnostic, 2 = poor, 3 = adequate, 4 = good, 5 = excellent) was significantly (P < 0.001) higher for wideband (3.7 ± 0.8) than for standard LGE MRI (2.1 ± 0.7). The mean artefact level score (1 = minimal, 2 = mild, 3 = moderate, 4 = severe, 5 = nondiagnostic) was significantly (P < 0.001) lower for wideband (2.1 ± 0.8) than for standard LGE MRI (4.0 ± 0.6). Wideband LGE MRI agreed better with gross pathology than standard LGE MRI. Conclusion This study demonstrates the feasibility of wideband LGE MRI for suppression of image artefacts induced by ICD at 3T. PMID:25336666

Impact of basal inferolateral scar burden determined by automatic analysis of 99mTc-MIBI myocardial perfusion SPECT on the long-term prognosis of cardiac resynchronization therapy.

PubMed

Morishima, Itsuro; Okumura, Kenji; Tsuboi, Hideyuki; Morita, Yasuhiro; Takagi, Kensuke; Yoshida, Ruka; Nagai, Hiroaki; Tomomatsu, Toshiro; Ikai, Yoshihiro; Terada, Kazushi; Sone, Takahito; Murohara, Toyoaki

2017-04-01

Left-ventricular (LV) scarring may be associated with a poor response to cardiac resynchronization therapy (CRT). The automatic analysis of myocardial perfusion single-photon emission computed tomography (MP-SPECT) may provide objective quantification of LV scarring. We investigated the impact of LV scarring determined by an automatic analysis of MP-SPECT on short-term LV volume response as well as long-term outcome. We studied consecutive 51 patients who were eligible to undergo 99mTc-MIBI MP-SPECT both at baseline and 6 months after CRT (ischaemic cardiomyopathies 31%). Quantitative perfusion SPECT was used to evaluate the defect extent (an index of global scarring) and the LV 17-segment regional uptake ratio (an inverse index of regional scar burden). The primary outcome was the composite of overall mortality or first hospitalization for worsening heart failure. A high global scar burden and a low mid/basal inferolateral regional uptake ratio were associated with volume non-responders to CRT at 6 months. The basal inferolateral regional uptake ratio remained as a predictor of volume non-response after adjusting for the type of cardiomyopathy. During a median follow-up of 36.1 months, the outcome occurred in 28 patients. The patients with a low basal inferolateral regional uptake ratio with a cutoff value of 57% showed poor prognosis (log-rank P= 0.006). The scarring determined by automatic analysis of MP-SPECT images may predict a poor response to CRT regardless of the pathogenesis of cardiomyopathy. The basal inferolateral scar burden in particular may have an adverse impact on long-term prognosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Mechanical regulation of fibroblast migration and collagen remodelling in healing myocardial infarcts

PubMed Central

Rouillard, Andrew D; Holmes, Jeffrey W

2012-01-01

Effective management of healing and remodelling after myocardial infarction is an important problem in modern cardiology practice. We have recently shown that the level of infarct anisotropy is a critical determinant of heart function following a large anterior infarction, which suggests that therapeutic gains may be realized by controlling infarct anisotropy. However, factors regulating infarct anisotropy are not well understood. Mechanical, structural and chemical guidance cues have all been shown to regulate alignment of fibroblasts and collagen in vitro, and prior studies have proposed that each of these cues could regulate anisotropy of infarct scar tissue, but understanding of fibroblast behaviour in the complex environment of a healing infarct is lacking. We developed an agent-based model of infarct healing that accounted for the combined influence of these cues on fibroblast alignment, collagen deposition and collagen remodelling. We pooled published experimental data from several sources in order to determine parameter values, then used the model to test the importance of each cue for predicting collagen alignment measurements from a set of recent cryoinfarction experiments. We found that although chemokine gradients and pre-existing matrix structures had important effects on collagen organization, a response of fibroblasts to mechanical cues was critical for correctly predicting collagen alignment in infarct scar. Many proposed therapies for myocardial infarction, such as injection of cells or polymers, alter the mechanics of the infarct region. Our modelling results suggest that such therapies could change the anisotropy of the healing infarct, which could have important functional consequences. This model is therefore a potentially important tool for predicting how such interventions change healing outcomes. PMID:22495588

Gene manipulated peritoneal cell patch repairs infarcted myocardium

PubMed Central

Huang, Wei; Zhang, Dongsheng; Millard, Ronald W.; Wang, Tao; Zhao, Tiemin; Fan, Guo-Chang; Ashraf, Atif; Xu, Meifeng; Ashraf, Muhammad; Wang, Yigang

2010-01-01

A gene manipulated cell patch using a homologous peritoneum substrate was developed and applied after myocardial infarction to repair scarred myocardium. We genetically engineered male rat mesenchymal stem cells (MSC) using adenoviral transduction to over-express CXCR4/green fluorescent protein (GFP) (MSCCXCR4) or MSCNull or siRNA targeting CXCR4 (MSCsiRNA). Gene expression was studied by real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). Cells were cultured on excised peritoneum for 9 days. Two weeks after left anterior descending (LAD) coronary artery ligation in female hearts, the peritoneum patch was applied over the scarred myocardium, cell side down. Efficacy of engraftment was determined by presence of GFP positive cells. One month after cell implantation, echocardiography was performed and hearts were harvested for histological analysis. Left ventricle (LV) fibrosis, LV anterior wall thickness (AWT) and blood vessel density at the margins of the graft were measured. There was significant up-regulation of the chemokines in the MSCCXCR4 group cultured under normoxic conditions when compared to the MSCNull group and a further increase was observed after exposure to hypoxia. One month after cell transplantation with the peritoneum patch, substantial numbers of GFP-positive cells were observed in and around the infarcted myocardium in MSCCXCR4 group. LV AWT, LV fibrosis and LV function were significantly improved in the MSCCXCR4 group as compared to these same variables in the MSCNull control. These salutary effects were absent in MSCsiRNA group. The gene manipulated MSC-seeded peritoneum patch promotes tissue nutrition (angiogenesis), reduces myocardial remodeling, and enhances heart function after myocardial infarction. PMID:19913551

Influence of Intramyocardial Adipose Tissue on the Accuracy of Endocardial Contact Mapping of the Chronic Myocardial Infarction Substrate.

PubMed

Samanta, Rahul; Kumar, Saurabh; Chik, William; Qian, Pierre; Barry, Michael A; Al Raisi, Sara; Bhaskaran, Abhishek; Farraha, Melad; Nadri, Fazlur; Kizana, Eddy; Thiagalingam, Aravinda; Kovoor, Pramesh; Pouliopoulos, Jim

2017-10-01

Recent studies have demonstrated that intramyocardial adipose tissue (IMAT) may contribute to ventricular electrophysiological remodeling in patients with chronic myocardial infarction. Using an ovine model of myocardial infarction, we aimed to determine the influence of IMAT on scar tissue identification during endocardial contact mapping and optimal voltage-based mapping criteria for defining IMAT dense regions. In 7 sheep, left ventricular endocardial and transmural mapping was performed 84 weeks (15-111 weeks) post-myocardial infarction. Spearman rank correlation coefficient was used to assess the relationship between endocardial contact electrogram amplitude and histological composition of myocardium. Receiver operator characteristic curves were used to derive optimal electrogram thresholds for IMAT delineation during endocardial mapping and to describe the use of endocardial mapping for delineation of IMAT dense regions within scar. Endocardial electrogram amplitude correlated significantly with IMAT (unipolar r =-0.48±0.12, P <0.001; bipolar r =-0.45±0.22, P =0.04) but not collagen (unipolar r =-0.36±0.24, P =0.13; bipolar r =-0.43±0.31, P =0.16). IMAT dense regions of myocardium reliably identified using endocardial mapping with thresholds of <3.7 and <0.6 mV, respectively, for unipolar, bipolar, and combined modalities (single modality area under the curve=0.80, P <0.001; combined modality area under the curve=0.84, P <0.001). Unipolar mapping using optimal thresholding remained significantly reliable (area under the curve=0.76, P <0.001) during mapping of IMAT, confined to putative scar border zones (bipolar amplitude, 0.5-1.5 mV). These novel findings enhance our understanding of the confounding influence of IMAT on endocardial scar mapping. Combined bipolar and unipolar voltage mapping using optimal thresholds may be useful for delineating IMAT dense regions of myocardium, in postinfarct cardiomyopathy. © 2017 American Heart Association, Inc.

Elastin overexpression by cell-based gene therapy preserves matrix and prevents cardiac dilation

PubMed Central

Li, Shu-Hong; Sun, Zhuo; Guo, Lily; Han, Mihan; Wood, Michael F G; Ghosh, Nirmalya; Alex Vitkin, I; Weisel, Richard D; Li, Ren-Ke

2012-01-01

After a myocardial infarction, thinning and expansion of the fibrotic scar contribute to progressive heart failure. The loss of elastin is a major contributor to adverse extracellular matrix remodelling of the infarcted heart, and restoration of the elastic properties of the infarct region can prevent ventricular dysfunction. We implanted cells genetically modified to overexpress elastin to re-establish the elastic properties of the infarcted myocardium and prevent cardiac failure. A full-length human elastin cDNA was cloned, subcloned into an adenoviral vector and then transduced into rat bone marrow stromal cells (BMSCs). In vitro studies showed that BMSCs expressed the elastin protein, which was deposited into the extracellular matrix. Transduced BMSCs were injected into the infarcted myocardium of adult rats. Control groups received either BMSCs transduced with the green fluorescent protein gene or medium alone. Elastin deposition in the infarcted myocardium was associated with preservation of myocardial tissue structural integrity (by birefringence of polarized light; P < 0.05 versus controls). As a result, infarct scar thickness and diastolic compliance were maintained and infarct expansion was prevented (P < 0.05 versus controls). Over a 9-week period, rats implanted with BMSCs demonstrated better cardiac function than medium controls; however, rats receiving BMSCs overexpressing elastin showed the greatest functional improvement (P < 0.01). Overexpression of elastin in the infarcted heart preserved the elastic structure of the extracellular matrix, which, in turn, preserved diastolic function, prevented ventricular dilation and preserved cardiac function. This cell-based gene therapy provides a new approach to cardiac regeneration. PMID:22435995

Reduced Collagen Deposition in Infarcted Myocardium Facilitates Induced Pluripotent Stem Cell Engraftment and Angiomyogenesis for Improvement of Left Ventricular Function

PubMed Central

Dai, Bo; Huang, Wei; Xu, Meifeng; Millard, Ronald W.; Gao, Mei Hua; Hammond, H. Kirk; Menick, Donald R.; Ashraf, Muhammad; Wang, Yigang

2012-01-01

Objectives The purpose of this study was to assess the effect of scar tissue composition on engraftment of progenitor cells into infarcted myocardium. Background Scar tissue formation after myocardial infarction creates a barrier that severely compromises tissue regeneration, limiting potential functional recovery. Methods In vitro: A tricell patch (Tri-P) was created from peritoneum seeded and cultured with induced pluripotent stem cell–derived cardiomyocytes, endothelial cells, and mouse embryonic fibroblasts. The expression of fibrosis-related molecules from mouse embryonic fibroblasts and infarcted heart was measured by Western blot and quantitative reverse transcriptase polymerase chain reaction. In vivo: A Tri-P was affixed over the entire infarcted area 7 days after myocardial infarction in mice overexpressing adenylyl cyclase 6 (AC6). Engraftment efficiency of progenitor cells in hearts of AC6 mice was compared with that of control wild-type (WT) mice using a combination of in vivo bioluminescence imaging, post-mortem ex vivo tissue analysis, and the number of green fluorescent protein–positive cells. Echocardiography of left ventricular (LV) function was performed weekly. Hearts were harvested for analysis 4 weeks after Tri-P application. Mouse embryonic fibroblasts were stimulated with forskolin before an anoxia/reoxygenation protocol. Fibrosis-related molecules were analyzed. Results In AC6 mice, infarcted hearts treated with Tri-P showed significantly higher bioluminescence imaging intensity and numbers of green fluorescent protein–positive cells than in WT mice. LV function improved progressively in AC6 mice from weeks 2 to 4 and was associated with reduced LV fibrosis. Conclusions Application of a Tri-P in AC6 mice resulted in significantly higher induced pluripotent stem cell engraftment accompanied by angiomyogenesis in the infarcted area and improvement in LV function. PMID:22051336

Interactive visualization for scar transmurality in cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Reiml, Sabrina; Toth, Daniel; Panayiotou, Maria; Fahn, Bernhard; Karim, Rashed; Behar, Jonathan M.; Rinaldi, Christopher A.; Razavi, Reza; Rhode, Kawal S.; Brost, Alexander; Mountney, Peter

2016-03-01

Heart failure is a serious disease affecting about 23 million people worldwide. Cardiac resynchronization therapy is used to treat patients suffering from symptomatic heart failure. However, 30% to 50% of patients have limited clinical benefit. One of the main causes is suboptimal placement of the left ventricular lead. Pacing in areas of myocardial scar correlates with poor clinical outcomes. Therefore precise knowledge of the individual patient's scar characteristics is critical for delivering tailored treatments capable of improving response rates. Current research methods for scar assessment either map information to an alternative non-anatomical coordinate system or they use the image coordinate system but lose critical information about scar extent and scar distribution. This paper proposes two interactive methods for visualizing relevant scar information. A 2-D slice based approach with a scar mask overlaid on a 16 segment heart model and a 3-D layered mesh visualization which allows physicians to scroll through layers of scar from endocardium to epicardium. These complementary methods enable physicians to evaluate scar location and transmurality during planning and guidance. Six physicians evaluated the proposed system by identifying target regions for lead placement. With the proposed method more target regions could be identified.

Novel cardiac magnetic resonance biomarkers: native T1 and extracellular volume myocardial mapping.

PubMed

Cannaò, Paola Maria; Altabella, Luisa; Petrini, Marcello; Alì, Marco; Secchi, Francesco; Sardanelli, Francesco

2016-04-28

Cardiac magnetic resonance (CMR) is a non-invasive diagnostic tool playing a key role in the assessment of cardiac morphology and function as well as in tissue characterization. Late gadolinium enhancement is a fundamental CMR technique for detecting focal or regional abnormalities such as scar tissue, replacement fibrosis, or inflammation using qualitative, semi-quantitative, or quantitative methods, but not allowing for evaluating the whole myocardium in the presence of diffuse disease. The novel T1 mapping approach permits a quantitative assessment of the entire myocardium providing a voxel-by-voxel map of native T1 relaxation time, obtained before the intravenous administration of gadolinium-based contrast material. Combining T1 data obtained before and after contrast injection, it is also possible to calculate the voxel-by-voxel extracellular volume (ECV), resulting in another myocardial parametric map. This article describes technical challenges and clinical perspectives of these two novel CMR biomarkers: myocardial native T1 and ECV mapping.

Role of nuclear cardiology in evaluating the total ischemic burden in coronary artery disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beller, G.A.

1987-03-09

Goals of exercise radionuclide imaging are to: enhance sensitivity, specificity and predictive value of coronary artery disease (CAD) detection; noninvasively assess extent and severity of functionally significant CAD; determine prognosis so that specific therapeutic strategies can be more rationally implemented; detect silent ischemia in asymptomatic subjects or in patients with known CAD with a higher degree of specificity than can be accomplished by electrocardiogram stress testing alone; evaluate the response to therapeutic interventions aimed at enhancing coronary blood flow. Two major radionuclide techniques are currently used in evaluating the total ischemic burden in patients with CAD. These are myocardial perfusionmore » imaging with either thallium-201 or rubidium-82, and radionuclide angiography performed after administration of technetium-99m. Areas of diminished thallium-201 activity on early postexercise images are abnormal and represent either areas of stress-induced ischemia or myocardial scar. To differentiate between the two, delayed images are obtained to determine if the initial postexercise defect either persists or demonstrates redistribution. Defects demonstrating redistribution represent transient ischemia, whereas areas of previous infarction or scar usually appear as persistent defects. Patients with left main or 3-vessel CAD usually show multiple thallium-201 redistribution defects in more than 1 vascular supply region, a phenomenon often associated with abnormal lung thallium-201 uptake.« less

Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction

PubMed Central

Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

2015-01-01

Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction. PMID:26074971

Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction.

PubMed

Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

2015-01-01

Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

Monitoring of Cardiac Remodeling in a Mouse Model of Pressure-Overload Left Ventricular Hypertrophy with [18F]FDG MicroPET.

PubMed

Todica, Andrei; Beetz, Nick L; Günther, Lisa; Zacherl, Mathias J; Grabmaier, Ulrich; Huber, Bruno; Bartenstein, Peter; Brunner, Stefan; Lehner, Sebastian

2018-04-01

This study aims to analyze the left ventricular function parameters, scar load, and hypertrophy in a mouse model of pressure-overload left ventricular (LV) hypertrophy over the course of 8 weeks using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) micro-positron emission tomography (microPET) imaging. LV hypertrophy was induced in C57BL/6 mice by transverse aortic constriction (TAC). Myocardial hypertrophy developed after 2-4 weeks. ECG-gated microPET scans with [ 18 F]FDG were performed 4 and 8 weeks after surgery. The extent of fibrosis was measured by histopathologic analysis. LV function parameters and scar load were calculated using QGS®/QPS®. LV metabolic volume (LVMV) and percentage injected dose per gram were estimated by threshold-based analysis. The fibrotic tissue volume increased significantly from 4 to 8 weeks after TAC (​1.67 vs. 3.91  mm 3 ; P = 0.044). There was a significant increase of the EDV (4 weeks: 54 ± 15 μl, 8 weeks: 79 ± 32 μl, P < 0.01) and LVMV (4 weeks: 222 ± 24 μl, 8 weeks: 276 ± 52 μl, P < 0.01) as well as a significant decrease of the LVEF (4 weeks: 56 ± 17 %, 8 weeks: 44 ± 20 %, P < 0.01). The increase of LVMV had a high predictive value regarding the amount of ex vivo measured fibrotic tissue (R = 0.905, P < 0.001). The myocardial metabolic defects increased within 4 weeks (P = 0.055) but only moderately correlated with the fibrosis volume (R = 0.502, P = 0.021). The increase in end-diastolic volume showed a positive correlation with the fibrosis at 8 weeks (R = 0.763, P = 0.017). [ 18 F]FDG-PET is applicable for serial in vivo monitoring of the TAC mouse model. Myocardial hypertrophy, the dilation of the left ventricle, and the decrease in LVEF could be reliably quantified over time, as well as the developing localized scar. The increase in volume over time is predictive of a high fibrosis load.

Scar Characterization to Predict Life-Threatening Arrhythmic Events and Sudden Cardiac Death in Patients With Cardiac Resynchronization Therapy: The GAUDI-CRT Study.

PubMed

Acosta, Juan; Fernández-Armenta, Juan; Borràs, Roger; Anguera, Ignasi; Bisbal, Felipe; Martí-Almor, Julio; Tolosana, Jose M; Penela, Diego; Andreu, David; Soto-Iglesias, David; Evertz, Reinder; Matiello, María; Alonso, Concepción; Villuendas, Roger; de Caralt, Teresa M; Perea, Rosario J; Ortiz, Jose T; Bosch, Xavier; Serra, Luis; Planes, Xavier; Greiser, Andreas; Ekinci, Okan; Lasalvia, Luis; Mont, Lluis; Berruezo, Antonio

2018-04-01

The aim of this study was to analyze whether scar characterization could improve the risk stratification for life-threatening ventricular arrhythmias and sudden cardiac death (SCD). Among patients with a cardiac resynchronization therapy (CRT) indication, appropriate defibrillator (CRT-D) therapy rates are low. Primary prevention patients with a class I indication for CRT were prospectively enrolled and assigned to CRT-D or CRT pacemaker according to physician's criteria. Pre-procedure contrast-enhanced cardiac magnetic resonance was obtained and analyzed to identify scar presence or absence, quantify the amount of core and border zone (BZ), and depict BZ distribution. The presence, mass, and characteristics of BZ channels in the scar were recorded. The primary endpoint was appropriate defibrillator therapy or SCD. 217 patients (39.6% ischemic) were included. During a median follow-up of 35.5 months (12 to 62 months), the primary endpoint occurred in 25 patients (11.5%) and did not occur in patients without myocardial scar. Among patients with scar (n = 125, 57.6%), those with implantable cardioverter-defibrillator (ICD) therapies or SCD exhibited greater scar mass (38.7 ± 34.2 g vs. 17.9 ± 17.2 g; p < 0.001), scar heterogeneity (BZ mass/scar mass ratio) (49.5 ± 13.0 vs. 40.1 ± 21.7; p = 0.044), and BZ channel mass (3.6 ± 3.0 g vs. 1.8 ± 3.4 g; p = 0.018). BZ mass (hazard ratio: 1.06 [95% confidence interval: 1.04 to 1.08]; p < 0.001) and BZ channel mass (hazard ratio: 1.21 [95% confidence interval: 1.10 to 1.32]; p < 0.001) were the strongest predictors of the primary endpoint. An algorithm based on scar mass and the absence of BZ channels identified 148 patients (68.2%) without ICD therapy/SCD during follow-up with a 100% negative predictive value. The presence, extension, heterogeneity, and qualitative distribution of BZ tissue of myocardial scar independently predict appropriate ICD therapies and SCD in CRT patients. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Multi-Ethnic Study of Atherosclerosis: Association between Left Atrial Function Using Tissue Tracking from Cine MR Imaging and Myocardial Fibrosis

PubMed Central

Imai, Masamichi; Ambale Venkatesh, Bharath; Samiei, Sanaz; Donekal, Sirisha; Habibi, Mohammadali; Armstrong, Anderson C.; Heckbert, Susan R.; Wu, Colin O.; Bluemke, David A.

2014-01-01

Purpose To investigate the association between left atrial (LAleft atrium) function and left ventricular myocardial fibrosis using cardiac magnetic resonance (MR) imaging in a multi-ethnic population. Materials and Methods For this HIPAA-compliant study, the institutional review board at each participating center approved the study protocol, and all participants provided informed consent. Of 2839 participants who had undergone cardiac MR in 2010–2012, 143 participants with myocardial scar determined with late gadolinium enhancement and 286 age-, sex-, and ethnicity-matched control participants were identified. LAleft atrium volume, strain, and strain rate were analyzed by using multimodality tissue tracking from cine MR imaging. T1 mapping was applied to assess diffuse myocardial fibrosis. The association between LAleft atrium parameters and myocardial fibrosis was evaluated with the Student t test and multivariable regression analysis. Results The scar group had significantly higher minimum LAleft atrium volume than the control group (mean, 22.0 ± 10.5 [standard deviation] vs 19.0 ± 7.8, P = .002) and lower LAleft atrium ejection fraction (45.9 ± 10.7 vs 51.3 ± 8.7, P < .001), maximal LAleft atrium strain (Smaxmaximum LA strain) (25.4 ± 10.7 vs 30.6 ± 10.6, P < .001) and maximum LAleft atrium strain rate (SRmaxmaximum LA strain rate) (1.08 ± 0.45 vs 1.29 ± 0.51, P < .001), and lower absolute LAleft atrium strain rate at early diastolic peak (SRELA strain rate at early diastolic peak) (−0.77 ± 0.42 vs −1.01 ± 0.48, P < .001) and LAleft atrium strain rate at atrial contraction peak (SRALA strain rate at atrial contraction peak) (−1.50 ± 0.62 vs −1.78 ± 0.69, P < .001) than the control group. T1 time 12 minutes after contrast material injection was significantly associated with Smaxmaximum LA strain (β coefficient = 0.043, P = .013), SRmaxmaximum LA strain rate (β coefficient = 0.0025, P = .001), SRELA strain rate at early diastolic peak (β coefficient = −0.0016, P = .027), and SRALA strain rate at atrial contraction peakLA strain rate at atrial contraction peak (β coefficient −0.0028, P = .01) in the regression model. T1 time 25 minutes after contrast material injection was significantly associated with SRmaxmaximum LA strain rate (β coefficient = 0.0019, P = .016) and SRALA strain rate at atrial contraction peak (β coefficient = −0.0022, P = .034). Conclusion Reduced LAleft atrium regional and global function are related to both replacement and diffuse myocardial fibrosis processes. Clinical trial registration no. NCT00005487 © RSNA, 2014 Online supplemental material is available for this article. PMID:25019562

Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function

PubMed Central

Saxena, Amit; Dobaczewski, Marcin; Rai, Vikrant; Haque, Zaffar; Chen, Wei; Li, Na

2014-01-01

Regulatory T cells (Tregs) play a pivotal role in suppressing immune responses regulating behavior and gene expression in effector T cells, macrophages, and dendritic cells. Tregs infiltrate the infarcted myocardium; however, their role the inflammatory and reparative response after myocardial infarction remains poorly understood. We used FoxP3EGFP reporter mice to study Treg trafficking in the infarcted heart and examined the effects of Treg depletion on postinfarction remodeling using an anti-CD25 antibody. Moreover, we investigated the in vitro effects of Tregs on cardiac fibroblast phenotype and function. Low numbers of Tregs infiltrated the infarcted myocardium after 24–72 h of reperfusion. Treg depletion had no significant effects on cardiac dysfunction and scar size after reperfused myocardial infarction but accelerated ventricular dilation and accentuated apical remodeling. Enhanced myocardial dilation in Treg-depleted animals was associated with increased expression of chemokine (C-C motif) ligand 2 and accentuated macrophage infiltration. In vitro, Tregs modulated the cardiac fibroblast phenotype, reducing expression of α-smooth muscle actin, decreasing expression of matrix metalloproteinase-3, and attenuating contraction of fibroblast-populated collagen pads. Our findings suggest that endogenous Tregs have modest effects on the inflammatory and reparative response after myocardial infarction. However, the anti-inflammatory and matrix-preserving properties of Tregs may suggest a role for Treg-based cell therapy in the attenuation of adverse postinfarction remodeling. PMID:25128167

Ischemic Ventricular Tachycardia Presenting as a Narrow Complex Tachycardia

PubMed Central

Page, Stephen P; Watts, Troy; Yeo, Wee Tiong; Mehul, Dhinoja

2014-01-01

This report describes a patient presenting with a narrow complex tachycardia in the context of prior myocardial infarction and impaired ventricular function. Electrophysiological studies confirmed ventricular tachycardia and activation and entrainment mapping demonstrated a critical isthmus within an area of scar involving the His-Purkinje system accounting for the narrow QRS morphology. This very rare case shares some similarities with upper septal ventricular tachycardia seen in patients with structurally normal hearts, but to our knowledge has not been seen previously in patients with ischemic heart disease. PMID:25057222

Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial.

PubMed

Nasseri, Boris A; Ebell, Wolfram; Dandel, Michael; Kukucka, Marian; Gebker, Rolf; Doltra, Adelina; Knosalla, Christoph; Choi, Yeong-Hoon; Hetzer, Roland; Stamm, Christof

2014-05-14

Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms. Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior. Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection. This trial was registered at http://www.clinicaltrials.gov under NCT00462774. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

CXC chemokine KC fails to induce neutrophil infiltration and neoangiogenesis in a mouse model of myocardial infarction.

PubMed

Oral, Hasan; Kanzler, Isabella; Tuchscheerer, Nancy; Curaj, Adelina; Simsekyilmaz, Sakine; Sönmez, Tolga Taha; Radu, Eugen; Postea, Otilia; Weber, Christian; Schuh, Alexander; Liehn, Elisa A

2013-07-01

Chemokines and neutrophils, known as important players in the inflammatory cascade, also contribute to heart tissue recovery and scar formation after myocardial infarction (MI). The objective of this study was to determine the importance of ELR-containing CXC chemokine KC in neutrophil infiltration and neoangiogenesis, in a mouse model of chronic MI. MI was induced in mice divided in four groups: control (untreated), anti-KC "later" (anti-KC antibody injections started 4 days after MI and then delivered every 72 hours for 3 weeks, to inhibit angiogenesis), anti-KC "earlier" (anti-KC antibody injections 1 day before and 1 day after MI, to block neutrophil infiltration), anti-KC (anti-KC antibody injections 1 day before and 1 day after MI, and then every 72 hours for 3 weeks). The efficiency of the anti-KC treatment was determined by the measurement of KC serum concentration and immunofluorescence staining, in each of the four groups. Surprisingly, we did not find any difference in neutrophil infiltration in the infarcted area between untreated and treated animals. Moreover, the heart function, infarct size, and neoangiogenesis were not different between the four groups. As expected, a comparable anti-CXCR2 treatment of mice before and after MI was able to significantly reduce neutrophil infiltration into the infarcted area and angiogenesis, but also to reduce the infarction size after long or "later" treatment. The major finding of our study is that KC, a potent neutrophil chemoattractant and an established angiogenic factor, failed to interfere in the post-infarction inflammatory response, in wound healing and scar formation after MI. Therefore, these aspects need to be carefully taken into account when devising therapeutic strategies for myocardial infarction and ischemic cardiomyopathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Alignment of human cardiomyocytes on laser patterned biphasic core/shell nanowire assemblies

NASA Astrophysics Data System (ADS)

Kiefer, Karin; Lee, Juseok; Haidar, Ayman; Martinez Miró, Marina; Akkan, Cagri Kaan; Veith, Michael; Cenk Aktas, Oral; Abdul-Khaliq, Hashim

2014-12-01

The management of end stage heart failure patients is only possible by heart transplantation or by the implantation of artificial hearts as a bridge for later transplantation. However, these therapeutic strategies are limited by a lack of donor hearts and by the associated complications, such as coagulation and infection, due to the used artificial mechanical circulatory assist devices. Therefore, new strategies for myocardial regenerative approaches are under extensive research to produce contractile myocardial tissue in the future to replace non-contractile myocardial ischemic and scarred tissue. Different approaches, such as cell transplantation, have been studied intensively. Although successful approaches have been observed, there are still limitations to the application. It is envisaged that myocardial tissue engineering can be used to help replace infarcted non-contractile tissue. The developed tissue should later mimic the aligned fibrillar structure of the extracellular matrix and provide important guidance cues for the survival, function and the needed orientation of cardiomyocytes. Nanostructured surfaces have been tested to provide a guided direction that cells can follow. In the present study, the cellular adhesion/alignment of human cardiomyocytes and the biocompatibility have been investigated after cultivation on different laser-patterned nanowires compared with unmodified nanowires. As a result, the nanostructured surfaces possessed good biocompatibility before and after laser modification. The laser-induced scalability of the pattern enabled the growth and orientation of the adhered myocardial tissue. Such approaches may be used to modify the surface of potential scaffolds to develop myocardial contractile tissue in the future.

Usefulness of MRI to Differentiate Between Temporary and Long-Term Coronary Artery Occlusion in a Minimally Invasive Model of Experimental Myocardial Infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abegunewardene, Nico, E-mail: nico@uni-mainz.de; Vosseler, Markus; Gori, Tommaso

The surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized to either temporary or permanent occlusion of the left anterior descending artery (LAD). Temporary occlusion was achieved by inflation of a percutaneous balloon in the left anterior descending artery directly beyond the second diagonal branch. Occlusion was maintained for 30 or 45 min, followed by reperfusion. Permanent occlusionmore » was achieved via thrombin injection. Thirteen animals died peri- or postinterventionally due to arrhythmias. Fourteen animals survived the 30-min ischemia (four animals; group 1), the 45-min ischemia (six animals; group 2), or the permanent occlusion (4 animals; group 3). Coronary angiography and ce-MRI were performed 8 weeks after coronary occlusion to document the coronary flow grade and the size of myocardial scar tissue. The LAD was patent in all animals in groups 1 and 2, with normal TIMI flow; in group 3 animals, the LAD was totally occluded. Fibrosis of the left ventricle in group 1 (4.9 {+-} 4.4%; p = 0.008) and group 2 (9.4 {+-} 2.9%; p = 0.05) was significantly lower than in group 3 (14.5 {+-} 3.9%). Wall thickness of the ischemic area was significantly lower in group 3 versus group 1 and group 2 (2.9 {+-} 0.3, 5.9 {+-} 0.7, and 6.1 {+-} 0.7 mm; p = 0.005). The extent of late enhancement of the left ventricle was also significantly higher in group 3 (16.9 {+-} 2.1%) compared to group 1 (5.3 {+-} 5.4%; p = 0.003) and group 2 (9.7 {+-} 3.4%, p = 0.013). In conclusion, the present model of minimally invasive infarction coupled with ce-MRI may represent a useful alternative to the open chest model for studies of myocardial infarction and scar development.« less

[Segmental wall movement of the left ventricle in healthy persons and myocardial infarct patients studied by a catheter-less nuclear medical method (camera-cinematography of the heart)].

PubMed

Geffers, H; Sigel, H; Bitter, F; Kampmann, H; Stauch, M; Adam, W E

1976-08-01

Camera-Kinematography is a nearly noninvasive method to investigate regional motion of the myocard, and allows evaluation of the function of the heart. About 20 min after injection of 15-20 mCi of 99mTC-Human-Serum-Albumin, when the tracer is distributed homogenously within the bloodpool, data acquisition starts. Myocardial wall motion is represented in an appropriate quasi three-dimensional form. In this representation scars can be revealed as "silent" (akinetic) regions, aneurysms by asynchronic motion. Time activity curves for arbitrarily chosen regions can be calculated and give an equivalent for regional volume changes. 16 patients with an old infarction have been investigated. In fourteen cases the location and extent of regions with abnormal motion could be evaluated. Only two cases of a small posterior wall infarction did not show deviations from normal contraction pattern.

[Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction].

PubMed

Strauer, B E; Brehm, M; Zeus, T; Gattermann, N; Hernandez, A; Sorg, R V; Kögler, G; Wernet, P

2001-08-24

The regenerative potential of human autologous adult stem cells on myocardial regeneration and neovascularisation after myocardial infarction may contribute to healing of the infarction area. But no clinical application has previously been reported. We here describe for the first time the results of this method applied in a patient who had sustained an acute myocardial infarction. 14 hours after the onset of left precordial pain a 46-year-old man was admitted to our hospital for interventional diagnosis and treatment. Coronary angiography demonstrated occlusion of the anterior descending branch of the left coronary artery with transmural infarction. This was treated by percutaneous transluminal catheter angioplasty and stent placement. Mononuclear bone marrow cells of the patient were prepared and 6 days after infaction 1,2 infinity 107 cells were transplanted at low pressure via a percutaneous transluminal catheter placed in the infarct-related artery. Before and 10 weeks after this procedure left ventricular function, infarct size, ventricular geometry and myocardial perfusion were measured by (201)thallium SPECT both at rest and on exercise, together with bull's-eye analysis, dobutamine stress echocardiography, right heart catheterisation and radionuclide ventriculography. At 10 weeks after the stem cell transplantation the transmural infarct area had been reduced from 24.6 % to 15.7 % of left ventricular circumference, while ejection fraction, cardiac index and stroke volume had increased by 20-30 %. On exercise the end diastolic volume had decreased by 30 % and there was a comparable fall in left ventricular filling pressure (mean pulmonary capillary pressure). These results for the first time demonstrate that selective intracoronary transplantation of human autologous adult stem cells is possible under clinical conditions and that it can lead to regeneration of the myocardial scar after transmural infarction. The therapeutic effects may be ascribed to stem cell-associated myocardial regeneration and neovascularisation.

The GSK-3 family as therapeutic target for myocardial diseases

PubMed Central

Lal, Hind; Ahmad, Firdos; Woodgett, James; Force, Thomas

2014-01-01

GSK-3 is one of the very few signaling molecules that regulate a truly astonishing number of critical intracellular signaling pathways. It has been implicated in a number of diseases including heart failure, bipolar disorder, diabetes, Alzheimer’s disease, aging, inflammation and cancer. Furthermore, a recent clinical trial has validated the feasibility of targeting GSK-3 with small molecule inhibitors for human diseases. In the current review we will focus on its expanding role in the heart, concentrating primarily on recent studies that have employed cardiomyocyte- and fibroblast-specific conditional gene deletion in mouse models. We will highlight the role of the GSK-3 isoforms in various pathological conditions including myocardial aging, ischemic injury, myocardial fibrosis and cardiomyocyte proliferation. We will discuss our recent findings that deletion of GSK-3α specifically in cardiomyocytes attenuates ventricular remodeling and cardiac dysfunction post-MI by limiting scar expansion and promoting cardiomyocyte proliferation. The recent emergence of GSK-3β as a regulator of myocardial fibrosis will also be discussed. We will review our very recent findings that specific deletion of GSK-3β in cardiac fibroblasts leads to fibrogenesis, left ventricular dysfunction and excessive scarring in the ischemic heart. Finally, we will examine the underlying mechanisms that drive the aberrant myocardial fibrosis in the models in which GSK-3β is specifically deleted in cardiac fibroblasts. We will summarize these recent results and offer explanations, whenever possible, and hypotheses when not. For these studies we will rely heavily on our models and those of others to reconcile some of the apparent inconsistencies in the literature. PMID:25552693

Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart

NASA Astrophysics Data System (ADS)

Mahoney, Vanessa M.; Mezzano, Valeria; Mirams, Gary R.; Maass, Karen; Li, Zhen; Cerrone, Marina; Vasquez, Carolina; Bapat, Aneesh; Delmar, Mario; Morley, Gregory E.

2016-05-01

Studies have demonstrated non-myocytes, including fibroblasts, can electrically couple to myocytes in culture. However, evidence demonstrating current can passively spread across scar tissue in the intact heart remains elusive. We hypothesize electrotonic conduction occurs across non-myocyte gaps in the heart and is partly mediated by Connexin43 (Cx43). We investigated whether non-myocytes in ventricular scar tissue are electrically connected to surrounding myocardial tissue in wild type and fibroblast-specific protein-1 driven conditional Cx43 knock-out mice (Cx43fsp1KO). Electrical coupling between the scar and uninjured myocardium was demonstrated by injecting current into the myocardium and recording depolarization in the scar through optical mapping. Coupling was significantly reduced in Cx43fsp1KO hearts. Voltage signals were recorded using microelectrodes from control scars but no signals were obtained from Cx43fsp1KO hearts. Recordings showed significantly decreased amplitude, depolarized resting membrane potential, increased duration and reduced upstroke velocity compared to surrounding myocytes, suggesting that the non-excitable cells in the scar closely follow myocyte action potentials. These results were further validated by mathematical simulations. Optical mapping demonstrated that current delivered within the scar could induce activation of the surrounding myocardium. These data demonstrate non-myocytes in the scar are electrically coupled to myocytes, and coupling depends on Cx43 expression.

Phagocyte-Myocyte Interactions and Consequences during Hypoxic Wound Healing

PubMed Central

Zhang, Shuang; Dehn, Shirley; DeBerge, Matthew; Rhee, KJ; Hudson, Barry; Thorp, Edward

2014-01-01

Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte phagocyte subsets to the damaged heart, the latter of which may give rise briefly to differentiated macrophage-like or dendritic-like cells. Within the injured myocardium, a primary function of these phagocytic cells is to remove damaged extracellular matrix, necrotic and apoptotic cardiac cells, as well as immune cells that turn over. Recognition of dying cellular targets by phagocytes triggers intracellular signaling, particularly in macrophages, wherein cytokines and lipid mediators are generated to promote inflammation resolution, fibrotic scarring, angiogenesis, and compensatory organ remodeling. These actions cooperate in an effort to preserve myocardial contractility and prevent heart failure. Immune cell function is modulated by local tissue factors that include secreted protease activity, oxidative stress during clinical reperfusion, and hypoxia. Importantly, experimental evidence suggests that monocyte function and phagocytosis efficiency is compromised in the setting of MI risk factors, including hyperlipidemia and ageing, however underlying mechanisms remain unclear. Herein we review seminal phagocyte and cardiac molecular factors that lead to, and culminate in, the recognition and removal of dying injured myocardium, the effects of hypoxia, and their relationship to cardiac infarct size and heart healing. PMID:24862542

In vivo cardiac cellular reprogramming efficacy is enhanced by angiogenic preconditioning of the infarcted myocardium with vascular endothelial growth factor.

PubMed

Mathison, Megumi; Gersch, Robert P; Nasser, Ahmed; Lilo, Sarit; Korman, Mallory; Fourman, Mitchell; Hackett, Neil; Shroyer, Kenneth; Yang, Jianchang; Ma, Yupo; Crystal, Ronald G; Rosengart, Todd K

2012-12-01

In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF-All6A(+)) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12 ± 2% vs 24 ± 3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4-fold. GMT-treated animals also demonstrated greater density of cardiomyocyte-specific marker beta myosin heavy chain 7(+) cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12 ± 3% vs -7 ± 3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4-fold greater in GMT/VEGF vs GMT/null animals (17 ± 2% vs 4 ± 1%, P<0.05). VEGF administration to infarcted myocardium enhances the efficacy of GMT-mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone.

Insights from Novel Noninvasive CT and ECG Imaging Modalities on Electromechanical Myocardial Activation in a Canine Model of Ischemic Dyssynchronous Heart Failure.

PubMed

Dawoud, Fady; Schuleri, Karl H; Spragg, David D; Horáček, B Milan; Berger, Ronald D; Halperin, Henry R; Lardo, Albert C

2016-12-01

The interplay between electrical activation and mechanical contraction patterns is hypothesized to be central to reduced effectiveness of cardiac resynchronization therapy (CRT). Furthermore, complex scar substrates render CRT less effective. We used novel cardiac computed tomography (CT) and noninvasive electrocardiographic imaging (ECGI) techniques in an ischemic dyssynchronous heart failure (DHF) animal model to evaluate electrical and mechanical coupling of cardiac function, tissue viability, and venous accessibility of target pacing regions. Ischemic DHF was induced in 6 dogs using coronary occlusion, left bundle ablation and tachy RV pacing. Full body ECG was recorded during native rhythm followed by volumetric first-pass and delayed enhancement CT. Regional electrical activation were computed and overlaid with segmented venous anatomy and scar regions. Reconstructed electrical activation maps show consistency with LBBB starting on the RV and spreading in a "U-shaped" pattern to the LV. Previously reported lines of slow conduction are seen parallel to anterior or inferior interventricular grooves. Mechanical contraction showed large septal to lateral wall delay (80 ± 38 milliseconds vs. 123 ± 31 milliseconds, P = 0.0001). All animals showed electromechanical correlation except dog 5 with largest scar burden. Electromechanical decoupling was largest in basal lateral LV segments. We demonstrated a promising application of CT in combination with ECGI to gain insight into electromechanical function in ischemic dyssynchronous heart failure that can provide useful information to study regional substrate of CRT candidates. © 2016 Wiley Periodicals, Inc.

[Morphological and electrophysiological changes of the heart atria in necropsy patients with atrial fibrillation - a pilot study].

PubMed

Matějková, Adéla; Steiner, Ivo

2014-01-01

Atrial fibrillation (AF), the most common supraventricular tachycardia, has a morphological base, so called remodelation of atrial myocardium, with its abnormal conduction pattern as a consequence. The remodelation regards electrical, contractile, and structural properties. In this pilot study we attempted to find relations between the myocardial morphological (scarring, amyloidosis, left atrial enlargement) and electrophysiological (ECG characteristics of the P-wave) changes in patients with AF. We examined 40 hearts of necropsy patients - 20 with a history of AF and 20 with no history of AF. Grossly, the heart weight and the size of the left atrium (LA) were evaluated. Histologically, 7 standard sites from the atria were examined. In each specimen, the degree of myocardial scarring and of deposition of isolated atrial amyloid (IAA) were assessed. We failed to show any significant difference in the P-wave pattern between patients with and without AF. Morphologically, however, there were several differences - the patients with AF had significantly heavier hearts, larger left atria, more severely scarred myocardium of the LA and the atrial septum, and more severe deposition of IAA in both atria in comparison to the control group of patients with sinus rhythm. The left atrial distribution of both fibrosis and amyloidosis was irregular. In patients with AF the former was most pronounced in the LA ceiling while the latter in the LA anterior wall. The entire series showed more marked amyloidosis in the left than in the right atrium. An interesting finding was the universal absence of IAA in the sinoatrial node. The knowledge of distribution of atrial myocardial structural changes could be utilized by pathologists in taking specimens for histology and also by cardiologists in targeting the radiofrequency ablation therapy.

Allogeneic Cardiospheres Delivered via Percutaneous Transendocardial Injection Increase Viable Myocardium, Decrease Scar Size, and Attenuate Cardiac Dilatation in Porcine Ischemic Cardiomyopathy

PubMed Central

Tseliou, Eleni; Cheng, Ke; Luthringer, Daniel J.; Ho, Chak-Sum; Takayama, Kentaro; Minamino, Naoto; Dawkins, James F.; Chowdhury, Supurna; Duong, Doan Trang; Seinfeld, Jeffrey; Middleton, Ryan C.; Dharmakumar, Rohan; Li, Debiao; Marbán, Linda; Makkar, Raj R.; Marbán, Eduardo

2014-01-01

Background Epicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy. Methods and Results We studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled (“dose optimization”) study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled (“pivotal”) study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo. Conclusions Dose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration. PMID:25460005

Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction.

PubMed

Liu, Xiaoli; Simpson, Jeremy A; Brunt, Keith R; Ward, Christopher A; Hall, Sean R R; Kinobe, Robert T; Barrette, Valerie; Tse, M Yat; Pang, Stephen C; Pachori, Alok S; Dzau, Victor J; Ogunyankin, Kofo O; Melo, Luis G

2007-07-01

We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.

Hibernating myocardium, morphological studies on intraoperatory myocardial biopsies and on chronic ischemia experimental model.

PubMed

Laky, D; Parascan, Liliana

2007-01-01

Hibernating myocardium represent a prolonged but potentially reversible myocardial contractile dysfunction, an incomplete adaptation caused by chronic myocardial ischemia and persisting at least until blood flow restored. The purpose of this study was to investigate the morphological changes and weather relations exist among function, metabolism and structure in left ventricular hibernating myocardium. Material and methods. Experimental study is making on 12 dogs incomplete coronary obstruction during six weeks for morphologic studies of ischemic zones. On 48 patients with coronary stenosis myocardial biopsies was effectuated during aorto-coronarian bypass graft. On 60 patients with valvular disease associated with segmental coronary atherosclerotic obstructions during surgical interventions on a effectuated repeatedly biopsies from ischemic zones. Dyskinetic ischemic areas was identified by angiography, scintigraphy, low dose dobutamine echography to identify the cells viability. On myocardial biopsies various histological, histoenzymological, immunohistochemical and ultrastructural methods were performed. The morphological cardiomyocytic changes can summarized: loss of myofilaments, accumulation of glycogen, small mitochondria with reversible lesions, decrease of smooth reticulum, absence of T tubules, depression of titin in puncted pattern, loss of cardiotonin, disorganization of cytoskeleton, dispersed nuclear heterochromatin, embryofetal dedifferentiation, and persistence of viability. Extracellular matrix is enlarged with early matrix protein such fibronectin, tenascin, fibroblasts. In experimental material the morphological changes present similarities with the human biopsies, but intermixed with postinfarction scar tissue. Redifferentiation of hibernanting cells end remodeling of extracellular matrix is possible after quigle revascularization through aorto-coronary bypass grafts.

Nonischemic left ventricular scar and cardiac sudden death in the young.

PubMed

di Gioia, Cira R T; Giordano, Carla; Cerbelli, Bruna; Pisano, Annalinda; Perli, Elena; De Dominicis, Enrico; Poscolieri, Barbara; Palmieri, Vincenzo; Ciallella, Costantino; Zeppilli, Paolo; d'Amati, Giulia

2016-12-01

Nonischemic left ventricular scar (NLVS) is a pattern of myocardial injury characterized by midventricular and/or subepicardial gadolinium hyperenhancement at cardiac magnetic resonance, in absence of significant coronary artery disease. We aimed to evaluate the prevalence of NLVS in juvenile sudden cardiac death and to ascertain its etiology at autopsy. We examined 281 consecutive cases of sudden death of subjects aged 1 to 35 years. NLVS was defined as a thin, gray rim of subepicardial and/or midmyocardial scar in the left ventricular free wall and/or the septum, in absence of significant stenosis of coronary arteries. NLVS was the most frequent finding (25%) in sudden deaths occurring during sports. Myocardial scar was localized most frequently within the left ventricular posterior wall and affected the subepicardial myocardium, often extending to the midventricular layer. On histology, it consisted of fibrous or fibroadipose tissue. Right ventricular involvement was always present. Patchy lymphocytic infiltrates were frequent. Genetic and molecular analyses clarified the etiology of NLVS in a subset of cases. Electrocardiographic (ECG) recordings were available in more than half of subjects. The most frequent abnormality was the presence of low QRS voltages (<0.5 mV) in limb leads. In serial ECG tracings, the decrease in QRS voltages appeared, in some way, progressive. NLVS is the most frequent morphologic substrate of juvenile cardiac sudden death in sports. It can be suspected based on ECG findings. Autopsy study and clinical screening of family members are required to differentiate between arrhythmogenic right ventricular cardiomyopathy/dysplasia and chronic acquired myocarditis. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional, morphological and electrocardiographical abnormalities in patients with apical hypertrophic cardiomyopathy and apical aneurysm: correlation with cardiac MR

PubMed Central

Suwa, Kenichiro; Satoh, Hiroshi; Sano, Makoto; Nobuhara, Mamoru; Saitoh, Takeji; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Tawarahara, Kei; Ohtani, Hayato; Wakabayashi, Yasushi; Takase, Hiroyuki; Terada, Hajime; Takehara, Yasuo; Sakahara, Harumi; Hayashi, Hideharu

2014-01-01

Objective The prognosis of apical hypertrophic cardiomyopathy (APH) has been benign, but apical myocardial injury has prognostic importance. We studied functional, morphological and electrocardiographical abnormalities in patients with APH and with apical aneurysm and sought to find parameters that relate to apical myocardial injury. Methods Study design: a multicentre trans-sectional study. Patients: 45 patients with APH and 5 with apical aneurysm diagnosed with transthoracic echocardiography (TTE) in the database of Hamamatsu Circulation Forum. Measure: the apical contraction with cine-cardiac MR (CMR), the myocardial fibrotic scar with late gadolinium enhancement (LGE)-CMR, and QRS fragmentation (fQRS) defined when two ECG-leads exhibited RSR’s patterns. Results Cine-CMR revealed 27 patients with normal, 12 with hypokinetic and 11 with dyskinetic apical contraction. TTE misdiagnosed 11 (48%) patients with hypokinetic and dyskinetic contraction as those with normal contraction. Apical LGE was apparent in 10 (83%) and 11 (100%) patients with hypokinetic and dyskinetic contraction, whereas only in 11 patients (41%) with normal contraction (p<0.01). Patients with dyskinetic apical contraction had the lowest left ventricular ejection fraction, the highest prevalence of ventricular tachycardia, and the smallest ST depression and depth of negative T waves. The presence of fQRS was associated with impaired apical contraction and apical LGE (OR=8.32 and 8.61, p<0.05). Conclusions CMR is superior to TTE for analysing abnormalities of the apex in patients with APH and with apical aneurysm. The presence of fQRS can be a promising parameter for the early detection of apical myocardial injury. PMID:25332823

Fibroblasts in myocardial infarction: a role in inflammation and repair

PubMed Central

Shinde, Arti V.; Frangogiannis, Nikolaos G.

2014-01-01

Fibroblasts do not only serve as matrix-producing reparative cells, but exhibit a wide range of functions in inflammatory and immune responses, angiogenesis and neoplasia. The adult mammalian myocardium contains abundant fibroblasts enmeshed within the interstitial and perivascular extracellular matrix. The current review manuscript discusses the dynamic phenotypic and functional alterations of cardiac fibroblasts following myocardial infarction. Extensive necrosis of cardiomyocytes in the infarcted heart triggers an intense inflammatory reaction. In the early stages of infarct healing, fibroblasts become pro-inflammatory cells, activating the inflammasome and producing cytokines, chemokines and proteases. Pro-inflammatory cytokines (such as Interleukin-1) delay myofibroblast transformation, until the wound is cleared from dead cells and matrix debris. Resolution of the inflammatory infiltrate is associated with fibroblast migration, proliferation, matrix protein synthesis and myofibroblast conversion. Growth factors and matricellular proteins play an important role in myofibroblast activation during the proliferative phase of healing. Formation of a mature cross-linked scar is associated with clearance of fibroblasts, as poorly-understood inhibitory signals restrain the fibrotic response. However, in the non-infarcted remodeling myocardium, local fibroblasts may remain activated in response to volume and pressure overload and may promote interstitial fibrosis. Considering their abundance, their crucial role in cardiac inflammation and repair, and their involvement in myocardial dysfunction and arrhythmogenesis, cardiac fibroblasts may be key therapeutic targets in cardiac remodeling. PMID:24321195

Influence of pacing site characteristics on response to cardiac resynchronization therapy.

PubMed

Wong, Jorge A; Yee, Raymond; Stirrat, John; Scholl, David; Krahn, Andrew D; Gula, Lorne J; Skanes, Allan C; Leong-Sit, Peter; Klein, George J; McCarty, David; Fine, Nowell; Goela, Aashish; Islam, Ali; Thompson, Terry; Drangova, Maria; White, James A

2013-07-01

Transmural scar occupying left ventricular (LV) pacing regions has been associated with reduced response to cardiac resynchronization therapy (CRT). However, spatial influences of lead tip delivery relative to scar at both pacing sites remain poorly explored. This study evaluated scar distribution relative to LV and right ventricular (RV) lead tip placement through coregistration of late gadolinium enhancement MRI and cardiac computed tomographic (CT) findings. Influences on CRT response were assessed by serial echocardiography. Sixty patients receiving CRT underwent preimplant late gadolinium enhancement MRI, postimplant cardiac CT, and serial echocardiography. Blinded segmental evaluations of mechanical delay, percentage scar burden, and lead tip location were performed. Response to CRT was defined as a reduction in LV end-systolic volume ≥15% at 6 months. The mean age and LV ejection fraction were 64±9 years and 25±7%, respectively. Mean scar volume was higher among CRT nonresponders for both the LV (23±23% versus 8±14% [P=0.01]) and RV pacing regions (40±32% versus 24±30% [P=0.04]). Significant pacing region scar was identified in 13% of LV pacing regions and 37% of RV pacing regions. Absence of scar in both regions was associated with an 81% response rate compared with 55%, 25%, and 0%, respectively, when the RV, LV, or both pacing regions contained scar. LV pacing region dyssynchrony was not predictive of response. Myocardial scar occupying the LV pacing region is associated with nonresponse to CRT. Scar occupying the RV pacing region is encountered at higher frequency and seems to provide a more intermediate influence on CRT response.

Reparative resynchronization in ischemic heart failure: an emerging strategy.

PubMed

Yamada, Satsuki; Terzic, Andre

2014-08-01

Cardiac dyssynchrony refers to disparity in cardiac wall motion, a serious consequence of myocardial infarction associated with poor outcome. Infarct-induced scar is refractory to device-based cardiac resynchronization therapy, which relies on viable tissue. Leveraging the prospect of structural and functional regeneration, reparative resynchronization has emerged as a potentially achievable strategy. In proof-of-concept studies, stem-cell therapy eliminates contractile deficit originating from infarcted regions and secures long-term synchronization with tissue repair. Limited clinical experience suggests benefit of cell interventions in acute and chronic ischemic heart disease as adjuvant to standard of care. A regenerative resynchronization option for dyssynchronous heart failure thus merits validation.

The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease.

PubMed

Moon, James C; Sheppard, Mary; Reed, Emma; Lee, Phillip; Elliott, Perry M; Pennell, Dudley J

2006-01-01

Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic death. The reasons for this distribution of fibrosis are unclear, but may reflect inhomogeneous left ventricular wall stress.

Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair.

PubMed

Zhu, Kai; Lai, Hao; Guo, Changfa; Li, Jun; Wang, Yulin; Wang, Lingyan; Wang, Chunsheng

2014-01-01

Mesenchymal stem cell (MSC) transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2) silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine) (Arg-G4) nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair.

Hippo pathway deficiency reverses systolic heart failure after infarction.

PubMed

Leach, John P; Heallen, Todd; Zhang, Min; Rahmani, Mahdis; Morikawa, Yuka; Hill, Matthew C; Segura, Ana; Willerson, James T; Martin, James F

2017-10-12

Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene, Park2. Genetic studies indicate that Park2 is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding Salv short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.

Phagocyte-myocyte interactions and consequences during hypoxic wound healing.

PubMed

Zhang, Shuang; Dehn, Shirley; DeBerge, Matthew; Rhee, Ki-Jong; Hudson, Barry; Thorp, Edward B

2014-01-01

Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte phagocyte subsets to the damaged heart, the latter of which may give rise briefly to differentiated macrophage-like or dendritic-like cells. Within the injured myocardium, a primary function of these phagocytic cells is to remove damaged extracellular matrix, necrotic and apoptotic cardiac cells, as well as immune cells that turn over. Recognition of dying cellular targets by phagocytes triggers intracellular signaling, particularly in macrophages, wherein cytokines and lipid mediators are generated to promote inflammation resolution, fibrotic scarring, angiogenesis, and compensatory organ remodeling. These actions cooperate in an effort to preserve myocardial contractility and prevent heart failure. Immune cell function is modulated by local tissue factors that include secreted protease activity, oxidative stress during clinical reperfusion, and hypoxia. Importantly, experimental evidence suggests that monocyte function and phagocytosis efficiency is compromised in the setting of MI risk factors, including hyperlipidemia and ageing, however underlying mechanisms remain unclear. Herein we review seminal phagocyte and cardiac molecular factors that lead to, and culminate in, the recognition and removal of dying injured myocardium, the effects of hypoxia, and their relationship to cardiac infarct size and heart healing. Copyright © 2014 Elsevier Inc. All rights reserved.

Dual ACE-inhibition and angiotensin II AT1 receptor antagonism with curcumin attenuate maladaptive cardiac repair and improve ventricular systolic function after myocardial infarctionin rat heart.

PubMed

Pang, Xue-Fen; Zhang, Li-Hui; Bai, Feng; Wang, Ning-Ping; Ijaz Shah, Ahmed; Garner, Ron; Zhao, Zhi-Qing

2015-01-05

Curcumin has been shown to improve cardiac function by reducing degradation of extracellular matrix and inhibiting synthesis of collagen after ischemia. This study tested the hypothesis that attenuation of maladaptive cardiac repair with curcumin is associated with a dual ACE-inhibition and angiotensin II AT1 receptor antagonism after myocardial infarction. Sprague-Dawley rats were subjected to 45min ischemia followed by 7 and 42 days of reperfusion, respectively. Curcumin was fed orally at a dose of 150mg/kg/day only during reperfusion. Relative to the control animals, dietary treatment with curcumin significantly reduced levels of ACE and AT1 receptor protein as determined by Western blot assay, coincident with less locally-expressed ACE and AT1 receptor in myocardium and coronary vessels as identified by immunohistochemistry. Along with this inhibition, curcumin significantly increased protein level of AT2 receptor and its expression compared with the control. As evidenced by less collagen deposition in fibrotic myocardium, curcumin also reduced the extent of collagen-rich scar and increased mass of viable myocardium detected by Masson׳s trichrome staining. Echocardiography showed that the wall thickness of the infarcted anterior septum in the curcumin group was significantly greater than that in the control group. Cardiac contractile function was improved in the curcumin treated animals as measured by fraction shortening and ejection fraction. In cultured cardiac muscle cells, curcumin inhibited oxidant-induced AT1 receptor expression and promoted cell survival. These results suggest that curcumin attenuates maladaptive cardiac repair and enhances cardiac function, primarily mediated by a dual ACE-inhibition and AT1 receptor antagonism after myocardial infarction. Copyright © 2014 Elsevier B.V. All rights reserved.

Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Hai-dong; Cui, Guo-hong; Yang, Jia-jun

Highlights: Black-Right-Pointing-Pointer The designer peptide LRKKLGKA could self-assemble into nanofibers. Black-Right-Pointing-Pointer Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. Thismore » designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.« less

Model study of imaging myocardial infarction by intracardiac electrical impedance tomography.

PubMed

Li, Ying; Rao, Liyun; Ling, Yuesheng; He, Renjie; Khoury, Dirar S

2008-01-01

Electrical impedance tomography (EIT) detects tissue composition inside a medium by determining its resistive properties, and uses various electrode configurations to pass a small electric current and measure corresponding potential. We investigated the feasibility of reconstructing scarred tissue inside the heart wall by employing EIT on the basis of a catheter carrying a plurality of electrodes and placed inside the blood-filled heart cavity. We built a computer model of the biological medium, and reconstructed the resistivity distribution using the finite element method and Tikhonov regularization. The results established the successful implementation of the numeric methods and the possibility of localizing and quantifying scarred myocardium. Novel application of EIT from inside the heart cavity could be useful during catheterization and may complement other diagnostic modalities. Further research is necessary to assess the impact of several factors on the accuracy of the reconstruction and include number of electrodes, catheter location, and scar size.

An injectable silk sericin hydrogel promotes cardiac functional recovery after ischemic myocardial infarction.

PubMed

Song, Yu; Zhang, Cheng; Zhang, Jinxiang; Sun, Ning; Huang, Kun; Li, Huili; Wang, Zheng; Huang, Kai; Wang, Lin

2016-09-01

Acute myocardial infarction (MI) leads to morbidity and mortality due to cardiac dysfunction. Here we identify sericin, a silk-derived protein, as an injectable therapeutic biomaterial for the minimally invasive MI repair. For the first time, sericin prepared in the form of an injectable hydrogel has been utilized for cardiac tissue engineering and its therapeutical outcomes evaluated in a mouse MI model. The injection of this sericin hydrogel into MI area reduces scar formation and infarct size, increases wall thickness and neovascularization, and inhibits the MI-induced inflammatory responses and apoptosis, thereby leading to a significant functional improvement. The potential therapeutical mechanisms have been further analyzed in vitro. Our results indicate that sericin downregulates pro-inflammatory cytokines (TNF-α and IL-18) and chemokine (CCL2) and reduces TNF-α expression by suppressing the TLR4-MAPK/NF-κB pathways. Moreover, sericin exhibits angiogenic activity by promoting migration and tubular formation of human umbilical vessel endothelial cells (HUVECs). Also, sericin stimulates VEGFa expression via activating ERK phosphorylation. Further, sericin protects endothelial cells and cardiomyocytes from apoptosis by inhibiting the activation of caspase 3. Together, these diverse biochemical activities of sericin protein lead to a significant recovery of cardiac function. This work represents the first study reporting sericin as an effective therapeutic biomaterial for ischemic myocardial repair in vivo. Intramyocardial biomaterial injection is thought to be a potential therapeutic approach to improve cardiac performance after ischemic myocardial infarction. In this study, we report the successful fabrication and in vivo application of an injectable sericin hydrogel for ischemic heart disease. We for the first time show that the injection of in situ forming crosslinked sericin hydrogel promotes heart functional recovery accompanied with reduced inflammatory responses, attenuated apoptosis and increased microvessel density in the infarcted hearts. Further, we reveal that the improvement in those aspects is ascribed to sericin protein's functional bioactivities that are comprehensively uncovered in this study. Thus, we identify sericin, a natural protein, as a biomaterial suitable for myocardial repair and demonstrate that the in vivo application of this injectable sericin hydrogel can be an effective strategy for treating MI. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Myocardial Viability and Impact of Surgical Ventricular Reconstruction on Outcomes of Patients with Severe Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery: Results of the Surgical Treatment for Ischemic Heart Failure (STICH) Trial

PubMed Central

Holly, Thomas A.; Bonow, Robert O.; Arnold, J. Malcolm O.; Oh, Jae K.; Varadarajan, Padmini; Pohost, Gerald M.; Haddad, Haissam; Jones, Robert H.; Velazquez, Eric J.; Birkenfeld, Bozena; Asch, Federico M.; Malinowski, Marcin; Barretto, Rodrigo; Kalil, Renato A.K.; Berman, Daniel S.; Sun, Jie-Lena; Lee, Kerry L.; Panza, Julio A.

2014-01-01

Objective In the Surgical Treatment for Ischemic Heart Failure (STICH) trial, surgical ventricular reconstruction plus coronary artery bypass surgery was not associated with a reduction in the rate of death or cardiac hospitalization compared to bypass alone. We hypothesized that the absence of viable myocardium identifies patients with coronary artery disease and left ventricular dysfunction who have a greater benefit with coronary artery bypass graft surgery and surgical ventricular reconstruction compared to bypass alone. Methods Myocardial viability was assessed by single photon computed tomography in 267 of the 1,000 patients randomized to bypass or bypass plus surgical ventricular reconstruction in STICH. Myocardial viability was assessed on a per patient basis as well as regionally based on pre-specified criteria. Results At 3 years, there was no difference in mortality or the combined outcome of death or cardiac hospitalization between those with and those without viability, and there was no significant interaction between the type of surgery and global viability status with respect to mortality or death plus cardiac hospitalization. Furthermore, there was no difference in mortality or death plus cardiac hospitalization between those with and without anterior wall or apical scar, and no significant interaction between the presence of scar in these regions and the type of surgery with respect to mortality. Conclusion In patients with coronary artery disease and severe regional left ventricular dysfunction, assessment of myocardial viability does not identify patients who will derive a mortality benefit from adding surgical ventricular reconstruction to coronary artery bypass graft surgery. PMID:25152476

Integrated Assessment of Left Ventricular Electrical Activation and Myocardial Strain Mapping in Heart Failure Patients: A Holistic Diagnostic Approach for Endocardial Cardiac Resynchronization Therapy, Ablation of Ventricular Tachycardia, and Biological Therapy.

PubMed

Maffessanti, Francesco; Prinzen, Frits W; Conte, Giulio; Regoli, François; Caputo, Maria Luce; Suerder, Daniel; Moccetti, Tiziano; Faletra, Francesco; Krause, Rolf; Auricchio, Angelo

2018-01-01

This study sought to test the accuracy of strain measurements based on anatomo-electromechanical mapping (AEMM) measurements compared with magnetic resonance imaging (MRI) tagging, to evaluate the diagnostic value of AEMM-based strain measurements in the assessment of myocardial viability, and the additional value of AEMM over peak-to-peak local voltages. The in vivo identification of viable tissue, evaluation of mechanical contraction, and simultaneous left ventricular activation is currently achieved using multiple complementary techniques. In 33 patients, AEMM maps (NOGA XP, Biologic Delivery Systems, Division of Biosense Webster, a Johnson & Johnson Company, Irwindale, California) and MRI images (Siemens 3T, Siemens Healthcare, Erlangen, Germany) were obtained within 1 month. MRI tagging was used to determine circumferential strain (E cc ) and delayed enhancement to obtain local scar extent (%). Custom software was used to measure E cc and local area strain (LAS) from the motion field of the AEMM catheter tip. Intertechnique agreement for E cc was good (R 2  = 0.80), with nonsignificant bias (0.01 strain units) and narrow limits of agreement (-0.03 to 0.06). Scar segments showed lower absolute strain amplitudes compared with nonscar segments: E cc (median [first to third quartile]: nonscar -0.10 [-0.15 to -0.06] vs. scar -0.04 [-0.06 to -0.02]) and LAS (-0.20 [-0.27 to -0.14] vs. -0.09 [-0.14 to -0.06]). AEMM strains accurately discriminated between scar and nonscar segments, in particular LAS (area under the curve: 0.84, accuracy = 0.76), which was superior to peak-to-peak voltages (nonscar 9.5 [6.5 to 13.3] mV vs. scar 5.6 [3.4 to 8.3] mV; area under the curve: 0.75). Combination of LAS and peak-to-peak voltages resulted in 86% accuracy. An integrated AEMM approach can accurately determine local deformation and correlates with the scar extent. This approach has potential immediate application in the diagnosis, delivery of intracardiac therapies, and their intraprocedural evaluation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Rationale and design of a multicentre, prospective, randomised, controlled clinical trial to evaluate the efficacy of the adipose graft transposition procedure in patients with a myocardial scar: the AGTP II trial.

PubMed

Gastelurrutia, Paloma; Gálvez-Montón, Carolina; Cámara, Maria Luisa; Bustamante-Munguira, Juan; García-Pavia, Pablo; Avanzas, Pablo; Alberto San Román, J; Pascual-Figal, Domingo; Teresa, Eduardo de; Crespo-Leiro, Maria G; Manito, Nicolás; Núñez, Julio; Fernández-Avilés, Francisco; Caballero, Ángel; Teis, Albert; Lupón, Josep; Brugada, Ramón; Martín, Carlos; Silva, Jacobo; Revilla-Orodea, Ana; Cánovas, Sergio J; Melero, Jose M; Cuenca-Castillo, Jose J; Gonzalez-Pinto, Angel; Bayes-Genis, Antoni

2017-08-04

Cardiac adipose tissue is a source of progenitor cells with regenerative capacity. Studies in rodents demonstrated that the intramyocardial delivery of cells derived from this tissue improves cardiac function after myocardial infarction (MI). We developed a new reparative approach for damaged myocardium that integrates the regenerative properties of cardiac adipose tissue with tissue engineering. In the adipose graft transposition procedure (AGTP), we dissect a vascularised flap of autologous pericardial adipose tissue and position it over the myocardial scarred area. Following encouraging results in acute and chronic MI porcine models, we performed the clinical trial (NCT01473433, AdiFLAP trial) to evaluate safety in patients with chronic MI undergoing coronary artery bypass graft. The good safety profile and trends in efficacy warranted a larger trial. The AGTP II trial (NCT02798276) is an investigator initiated, prospective, randomised, controlled, multicentre study to assess the efficacy of the AGTP in 108 patients with non-revascularisable MI. Patients will be assigned to standard clinical practice or the AGTP. The primary endpoint is change in necrotic mass ratio by gadolinium enhancement at 91 and 365 days. Secondary endpoints include improvement in regional contractibility by MRI at 91 and 365 days; changes in functional MRI parameters (left ventricular ejection fraction, left and right ventricular geometric remodelling) at 91 and 365 days; levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 7, 91 and 365 days; appearance of arrhythmias from 24 hour Holter monitoring at 24 hours, and at 91 and 365 days; all cause death or re-hospitalisation at 365 days; and cardiovascular death or re-hospitalisation at 365 days. The institutional review board approved the trial which will comply with the Declaration of Helsinki. All patients will provide informed consent. It may offer a novel, effective and technically simple technique for patients with no other therapeutic options. The results will be submitted to indexed medical journals and national and international meetings. ClinicalTrials.gov: NCT02798276, pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

In Vivo Cardiac Cellular Reprogramming Efficacy Is Enhanced by Angiogenic Preconditioning of the Infarcted Myocardium With Vascular Endothelial Growth Factor

PubMed Central

Mathison, Megumi; P. Gersch, Robert; Nasser, Ahmed; Lilo, Sarit; Korman, Mallory; Fourman, Mitchell; Hackett, Neil; Shroyer, Kenneth; Yang, Jianchang; Ma, Yupo; Crystal, Ronald G.; Rosengart, Todd K.

2012-01-01

Background In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. Methods and Results Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF‐All6A+) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12±2% vs 24±3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4‐fold. GMT‐treated animals also demonstrated greater density of cardiomyocyte‐specific marker beta myosin heavy chain 7+ cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12±3% vs −7±3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4‐fold greater in GMT/VEGF vs GMT/null animals (17±2% vs 4±1%, P<0.05). Conclusions VEGF administration to infarcted myocardium enhances the efficacy of GMT‐mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone. PMID:23316332

Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

PubMed

Liu, Xiaoli; Pachori, Alok S; Ward, Christopher A; Davis, J Paul; Gnecchi, Massimiliano; Kong, Deling; Zhang, Lunan; Murduck, Jared; Yet, Shaw-Fang; Perrella, Mark A; Pratt, Richard E; Dzau, Victor J; Melo, Luis G

2006-02-01

We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarction recovery has not been investigated. In the current study, we assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV) remodeling and function using echocardiographic imaging and histomorphometric approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11) particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene transfer, the animals were subjected to 30 min of ischemia by ligation of left anterior descending artery (LAD) followed by reperfusion. Echocardiographic measurements were obtained in a blinded fashion prior and at 1.5 and 3 months after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ groups, respectively at 1.5 months after MI. Three months after MI, EF recovered fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV dimensions were markedly increased and the anterior wall was markedly thinned in the LacZ-treated animals compared with the HO-1-treated animals. Significant myocardial scarring and fibrosis were observed in the LacZ-group in association with elevated levels of interstitial collagen I and III and MMP-2 activity. Post-MI myofibroblast accumulation was reduced in the HO-1-treated animals, and retroviral overexpression of HO-1 reduced proliferation of isolated cardiac fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces fibrosis and ventricular remodeling and restores LV function and chamber dimensions after myocardial infarction.

Scar Management of the Burned Hand

PubMed Central

Sorkin, Michael; Cholok, David; Levi, Benjamin

2017-01-01

Unimpaired hand function is critical in almost all activities of daily living. Burn injury can result in hypertrophic scar formation that can lead to debilitating functional deficits and poor aesthetic outcomes. Initial algorithms of acute burn management involve early debridement and skin grafting and early mobilization to prevent formation of hypertrophic scarring and ultimately digit contractures. While non-operative modalities in the early phase of scar maturation are critical to minimize hypertrophic scar formation, surgical management is often indicated in order to restore hand function. The essential tenant of operative scar management is release of tension, which can often be achieved through local tissue rearrangement. Laser therapy has emerged as a central pillar of subsequent scar rehabilitation with several modalities that address scar texture, color, pruritis and thickness. These can be utilized in conjunction with local corticosteroid treatment and other emerging modalities to modulate the scar and achieve optimal hand function. These treatment tools provide an effective resource for the reconstructive surgeon to treat hypertrophic hand scars. PMID:28363297

Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context

PubMed Central

Ajijola, Olujimi A.; Yagishita, Daigo; Patel, Krishan J.; Vaseghi, Marmar; Zhou, Wei; Yamakawa, Kentaro; So, Eileen; Lux, Robert L.; Mahajan, Aman

2013-01-01

Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n = 9) and control swine (n = 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 ± 8 vs. 436 ± 9 ms, P < 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 ± 123 vs. 362 ± 32 ms2, P = 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 ± 14 vs. 365 ± 8 ms, P = 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation (P = 0.0001), whereas left stellate ganglion stimulation showed the reverse (P = 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced. PMID:23893167

Complete cardiac regeneration in a mouse model of myocardial infarction.

PubMed

Haubner, Bernhard Johannes; Adamowicz-Brice, Martyna; Khadayate, Sanjay; Tiefenthaler, Viktoria; Metzler, Bernhard; Aitman, Tim; Penninger, Josef M

2012-12-01

Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remained entirely unclear whether the mammalian heart can also completely regenerate following a complex cardiac ischemic injury. We established a protocol to induce a severe heart attack in one-day-old mice using left anterior descending artery (LAD) ligation. LAD ligation triggered substantial cardiac injury in the left ventricle defined by Caspase 3 activation and massive cell death. Ischemia-induced cardiomyocyte death was also visible on day 4 after LAD ligation. Remarkably, 7 days after the initial ischemic insult, we observed complete cardiac regeneration without any signs of tissue damage or scarring. This tissue regeneration translated into long-term normal heart functions as assessed by echocardiography. In contrast, LAD ligations in 7-day-old mice resulted in extensive scarring comparable to adult mice, indicating that the regenerative capacity for complete cardiac healing after heart attacks can be traced to the first week after birth. RNAseq analyses of hearts on day 1, day 3, and day 10 and comparing LAD-ligated and sham-operated mice surprisingly revealed a transcriptional programme of major changes in genes mediating mitosis and cell division between days 1, 3 and 10 postnatally and a very limited set of genes, including genes regulating cell cycle and extracellular matrix synthesis, being differentially regulated in the regenerating hearts. We present for the first time a mammalian model of complete cardiac regeneration following a severe ischemic cardiac injury. This novel model system provides the unique opportunity to uncover molecular and cellular pathways that can induce cardiac regeneration after ischemic injury, findings that one day could be translated to human heart attack patients.

Cardiovascular Magnetic Resonance Findings Late After the Arterial Switch Operation.

PubMed

Shepard, Charles W; Germanakis, Ioannis; White, Matthew T; Powell, Andrew J; Co-Vu, Jennifer; Geva, Tal

2016-09-01

Despite its robust diagnostic capabilities in adolescents and adult patients after the arterial switch operation, little information is available on the cardiovascular magnetic resonance findings in this population. The cardiovascular magnetic resonance findings of 220 consecutive patients evaluated in our center were retrospectively reviewed (median age at cardiovascular magnetic resonance, 15.4 years; 66.8% male sex). Compared with published normal values, left and right ventricular end-diastolic volume z scores were mildly enlarged (0.48±1.76 and 0.33±1.5; P=0.0003 and 0.0038, respectively), with 26% of patients having left ventricular dilatation and 20% having right ventricular dilatation. Left ventricular dysfunction was present in 21.5% of patients (mild in most), and only 5.1% of patients had mild right ventricular dysfunction. Myocardial scar was found in 1.8% of patients. Dilatation of the neoaortic root was common (76%), and root z score increased at an average rate of 0.03 points per year. By multivariable analysis, neoaortic root dilatation was associated with worse neoaortic valve regurgitation (OR, 5.29; P=0.0016). The diameters of the thoracic aorta distal to the root were near-normal in most patients, whereas the neomain pulmonary artery was typically oval shaped with decreased anteroposterior and normal lateral diameters. Although the majority of arterial switch operation patients have normal ventricular size and function and myocardial scar is rare, an important minority exhibits ventricular enlargement or dysfunction. Neoaortic root dilatation, which is present in most patients and progresses over time, is strongly associated with significant neoaortic valve regurgitation. The findings of this study provide reference values against which arterial switch operation patients can be compared with their peers. © 2016 American Heart Association, Inc.

Cardiac tissue engineering: from matrix design to the engineering of bionic hearts.

PubMed

Fleischer, Sharon; Feiner, Ron; Dvir, Tal

2017-04-01

The field of cardiac tissue engineering aims at replacing the scar tissue created after a patient has suffered from a myocardial infarction. Various technologies have been developed toward fabricating a functional engineered tissue that closely resembles that of the native heart. While the field continues to grow and techniques for better tissue fabrication continue to emerge, several hurdles still remain to be overcome. In this review we will focus on several key advances and recent technologies developed in the field, including biomimicking the natural extracellular matrix structure and enhancing the transfer of the electrical signal. We will also discuss recent developments in the engineering of bionic cardiac tissues which integrate the fields of tissue engineering and electronics to monitor and control tissue performance.

Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) trial.

PubMed

Atar, Dan; Petzelbauer, Peter; Schwitter, Jürg; Huber, Kurt; Rensing, Benno; Kasprzak, Jaroslaw D; Butter, Christian; Grip, Lars; Hansen, Peter R; Süselbeck, Tim; Clemmensen, Peter M; Marin-Galiano, Marcos; Geudelin, Bernard; Buser, Peter T

2009-02-24

The purpose of this study was to investigate whether FX06 would limit infarct size when given as an adjunct to percutaneous coronary intervention. FX06, a naturally occurring peptide derived from human fibrin, has been shown to reduce myocardial infarct size in animal models by mitigating reperfusion injury. In all, 234 patients presenting with acute ST-segment elevation myocardial infarction were randomized in 26 centers. FX06 or matching placebo was given as intravenous bolus at reperfusion. Infarct size was assessed 5 days after myocardial infarction by late gadolinium enhanced cardiac magnetic resonance imaging. Secondary outcomes included size of necrotic core zone and microvascular obstruction at 5 days, infarct size at 4 months, left ventricular function, troponin I levels, and safety. There were no baseline differences between groups. On day 5, there was no significant difference in total late gadolinium enhanced zone in the FX06 group compared with placebo (reduction by 21%; p = 0.207). The necrotic core zone, however, was significantly reduced by 58% (median 1.77 g [interquartile range 0.0, 9.09 g] vs. 4.20 g [interquartile range 0.3, 9.93 g]; p < 0.025). There were no significant differences in troponin I levels (at 48 h, -17% in the FX06 group). After 4 months, there were no longer significant differences in scar size. There were numerically fewer serious cardiac events in the FX06-treated group, and no differences in adverse events. In this proof-of-concept trial, FX06 reduced the necrotic core zone as one measure of infarct size on magnetic resonance imaging, while total late enhancement was not significantly different between groups. The drug appears safe and well tolerated. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury [F.I.R.E.]; NCT00326976).

Paracrine Engineering of Human Cardiac Stem Cells With Insulin-Like Growth Factor 1 Enhances Myocardial Repair.

PubMed

Jackson, Robyn; Tilokee, Everad L; Latham, Nicholas; Mount, Seth; Rafatian, Ghazaleh; Strydhorst, Jared; Ye, Bin; Boodhwani, Munir; Chan, Vincent; Ruel, Marc; Ruddy, Terrence D; Suuronen, Erik J; Stewart, Duncan J; Davis, Darryl R

2015-09-11

Insulin-like growth factor 1 (IGF-1) activates prosurvival pathways and improves postischemic cardiac function, but this key cytokine is not robustly expressed by cultured human cardiac stem cells. We explored the influence of an enhanced IGF-1 paracrine signature on explant-derived cardiac stem cell-mediated cardiac repair. Receptor profiling demonstrated that IGF-1 receptor expression was increased in the infarct border zones of experimentally infarcted mice by 1 week after myocardial infarction. Human explant-derived cells underwent somatic gene transfer to overexpress human IGF-1 or the green fluorescent protein reporter alone. After culture in hypoxic reduced-serum media, overexpression of IGF-1 enhanced proliferation and expression of prosurvival transcripts and prosurvival proteins and decreased expression of apoptotic markers in both explant-derived cells and cocultured neonatal rat ventricular cardiomyocytes. Transplant of explant-derived cells genetically engineered to overexpress IGF-1 into immunodeficient mice 1 week after infarction boosted IGF-1 content within infarcted tissue and long-term engraftment of transplanted cells while reducing apoptosis and long-term myocardial scarring. Paracrine engineering of explant-derived cells to overexpress IGF-1 provided a targeted means of improving cardiac stem cell-mediated repair by enhancing the long-term survival of transplanted cells and surrounding myocardium. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

[The development of a computer model in the quantitative assessment of thallium-201 myocardial scintigraphy].

PubMed

Raineri, M; Traina, M; Rotolo, A; Candela, B; Lombardo, R M; Raineri, A A

1993-05-01

Thallium-201 scintigraphy is a widely used noninvasive procedure for the detection and prognostic assessment of patients with suspected or proven coronary artery disease. Thallium uptake can be evaluated by a visual analysis or by a quantitative interpretation. Quantitative scintigraphy enhances disease detection in individual coronary arteries, provides a more precise estimate of the amount of ischemic myocardium, distinguishing scar from hypoperfused tissue. Due to the great deal of data, analysis, interpretation and comparison of thallium uptake can be very complex. We designed a computer-based system for the interpretation of quantitative thallium-201 scintigraphy data uptake. We used a database (DataEase 4.2-DataEase Italia). Our software has the following functions: data storage; calculation; conversion of numerical data into different definitions classifying myocardial perfusion; uptake data comparison; automatic conclusion; comparison of different scintigrams for the same patient. Our software is made up by 4 sections: numeric analysis, descriptive analysis, automatic conclusion, clinical remarks. We introduced in the computer system appropriate information, "logical paths", that use the "IF ... THEN" rules. The software executes these rules in order to analyze the myocardial regions in the 3 phases of scintigraphic analysis (stress, redistribution, re-injection), in the 3 projections (LAO 45 degrees, LAT,ANT), considering our uptake cutoff, obtaining, finally, the automatic conclusions. For these reasons, our computer-based system could be considered a real "expert system".

Direct Cardiac Reprogramming as a Novel Therapeutic Strategy for Treatment of Myocardial Infarction.

PubMed

Ma, Hong; Wang, Li; Liu, Jiandong; Qian, Li

2017-01-01

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function. Our findings suggest that iCM reprogramming may be a means of regenerating functional CMs in vivo for patients with heart disease. However, because relatively little is known about the factors that regulate iCM reprogramming, the applicability of iCM reprogramming is currently limited to the experimental settings in which it has been attempted. Specific hurdles include the relatively low conversion rate of iCMs and the need for reprogramming to occur in the context of acute injury. Therefore, before this treatment can become a viable therapy for human heart disease, the optimal condition for efficient iCM generation must be determined. Here, we provide a detailed protocol for both in vitro and in vivo iCM generation that has been optimized so far in our lab. We hope that this protocol will lay a foundation for future further improvement of iCM generation and provide a platform for mechanistic studies.

An automatic alignment tool to improve repeatability of left ventricular function and dyssynchrony parameters in serial gated myocardial perfusion SPECT studies

PubMed Central

Zhou, Yanli; Faber, Tracy L.; Patel, Zenic; Folks, Russell D.; Cheung, Alice A.; Garcia, Ernest V.; Soman, Prem; Li, Dianfu; Cao, Kejiang; Chen, Ji

2013-01-01

Objective Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI. Methods Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters. Results The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing. Conclusion The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI. PMID:23211996

Effect of low-level laser-treated mesenchymal stem cells on myocardial infarction.

PubMed

El Gammal, Zaynab H; Zaher, Amr M; El-Badri, Nagwa

2017-09-01

Cardiovascular disease is the leading cause of death worldwide. Although cardiac transplantation is considered the most effective therapy for end-stage cardiac diseases, it is limited by the availability of matching donors and the complications of the immune suppressive regimen used to prevent graft rejection. Application of stem cell therapy in experimental animal models was shown to reverse cardiac remodeling, attenuate cardiac fibrosis, improve heart functions, and stimulate angiogenesis. The efficacy of stem cell therapy can be amplified by low-level laser radiation. It is well established that the bio-stimulatory effect of low-level laser is influenced by the following parameters: wavelength, power density, duration, energy density, delivery time, and the type of irradiated target. In this review, we evaluate the available experimental data on treatment of myocardial infarction using low-level laser. Eligible papers were characterized as in vivo experimental studies that evaluated the use of low-level laser therapy on stem cells in order to attenuate myocardial infarction. The following descriptors were used separately and in combination: laser therapy, low-level laser, low-power laser, stem cell, and myocardial infarction. The assessed low-level laser parameters were wavelength (635-804 nm), power density (6-50 mW/cm 2 ), duration (20-150 s), energy density (0.96-1 J/cm 2 ), delivery time (20 min-3 weeks after myocardial infarction), and the type of irradiated target (bone marrow or in vitro-cultured bone marrow mesenchymal stem cells). The analysis focused on the cardioprotective effect of this form of therapy, the attenuation of scar tissue, and the enhancement of angiogenesis as primary targets. Other effects such as cell survival, cell differentiation, and homing are also included. Among the evaluated protocols using different parameters, the best outcome for treating myocardial infarction was achieved by treating the bone marrow by one dose of low-level laser with 804 nm wavelength and 1 J/cm 2 energy density within 4 h of the infarction. This approach increased stem cell survival, proliferation, and homing. It has also decreased the infarct size and cell apoptosis, leading to enhanced heart functions. These effects were stable for 6 weeks. However, more studies are still required to assess the effects of low-level laser on the genetic makeup of the cell, the nuclei, and the mitochondria of mesenchymal stromal cells (MSCs).

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

PubMed Central

Gourdie, Robert G.; Dimmeler, Stefanie; Kohl, Peter

2016-01-01

Our understanding of cardiac fibroblast functions has moved beyond their roles in heart structure and extracellular matrix generation, and now includes contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation. Novel experimental approaches targeting cardiac fibroblasts are promising potential therapies for heart disease. Indeed, several existing drugs act, at least partially, through effects on cardiac connective tissue. This Review outlines the origins and roles of fibroblasts in cardiac development, homeostasis and disease; illustrates the involvement of fibroblasts in current and emerging clinical interventions; and identifies future targets for research and development. PMID:27339799

Clinical trials update from the Heart Failure Society of America Meeting 2009: FAST, IMPROVE-HF, COACH galectin-3 substudy, HF-ACTION nuclear substudy, DAD-HF, and MARVEL-1.

PubMed

Lainscak, Mitja; Coletta, Alison P; Sherwi, Nasser; Cleland, John G F

2010-02-01

This article presents findings and a commentary on late-breaking trials presented during the meeting of the Heart Failure Society of America in September 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The FAST trial showed somewhat better performance of intrathoracic impedance for prediction of deterioration in patients with heart failure (HF) when compared with daily weighing. The IMPROVE-HF study reported the benefits of education on the management of patients with systolic HF. Galectin-3 appeared a useful method for improving risk stratification of patients with chronic HF in a substudy of the COACH trial. A nuclear substudy of the HF-ACTION trial failed to demonstrate that resting myocardial perfusion imaging, a measure of myocardial scar and viability, was clinically useful. A small randomized controlled trial (DAD-HF) suggested that the use of low-dose dopamine in patients with acutely decompensated HF was associated with less deterioration in renal function and less hypokalaemia. The MARVEL-1 trial raises further concerns about the safety of myoblast transplantation in ischaemic HF.

Atrial fibrillation: effects beyond the atrium?

PubMed

Wijesurendra, Rohan S; Casadei, Barbara

2015-03-01

Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is associated with significant morbidity, mostly secondary to heart failure and stroke, and an estimated two-fold increase in premature death. Efforts to increase our understanding of AF and its complications have focused on unravelling the mechanisms of electrical and structural remodelling of the atrial myocardium. Yet, it is increasingly recognized that AF is more than an atrial disease, being associated with systemic inflammation, endothelial dysfunction, and adverse effects on the structure and function of the left ventricular myocardium that may be prognostically important. Here, we review the molecular and in vivo evidence that underpins current knowledge regarding the effects of human or experimental AF on the ventricular myocardium. Potential mechanisms are explored including diffuse ventricular fibrosis, focal myocardial scarring, and impaired myocardial perfusion and perfusion reserve. The complex relationship between AF, systemic inflammation, as well as endothelial/microvascular dysfunction and the effects of AF on ventricular calcium handling and oxidative stress are also addressed. Finally, consideration is given to the clinical implications of these observations and concepts, with particular reference to rate vs. rhythm control. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

A cryoinjury model in neonatal mice for cardiac translational and regeneration research

PubMed Central

Polizzotti, Brian D.; Ganapathy, Balakrishnan; Haubner, Bernhard; Penninger, Josef; Kühn, Bernhard

2017-01-01

The introduction of injury models for neonatal mouse hearts has accelerated research on the mechanisms of cardiac regeneration in mammals. However, some existing models such as apical resection and ligation of the left anterior descending artery produce variable results, which may be due to technical difficulties associated with these methods. Here, we present an alternative model for studying cardiac regeneration in neonatal mice in which cryoinjury is used to induce heart injury. This model yields a reproducible injury size, does not induce known mechanisms of cardiac regeneration, and leads to a sustained reduction of cardiac function. This protocol uses reusable cryoprobes that can be assembled in 5 minutes, with the entire procedure taking 15 minutes per pup. The subsequent heart collection and fixation takes 2 days to complete. Cryoinjury results in a myocardial scar, and the size of injury can be scaled by use of different cryoprobes (0.5 and 1.5 mm). Cryoinjury models are medically relevant to diseases in human infants with heart disease. In summary, the myocardial cryoinjury model in neonatal mice described here is a useful tool for cardiac translational and regeneration research. PMID:26890681

Targeting C-reactive protein for the treatment of cardiovascular disease

NASA Astrophysics Data System (ADS)

Pepys, Mark B.; Hirschfield, Gideon M.; Tennent, Glenys A.; Ruth Gallimore, J.; Kahan, Melvyn C.; Bellotti, Vittorio; Hawkins, Philip N.; Myers, Rebecca M.; Smith, Martin D.; Polara, Alessandra; Cobb, Alexander J. A.; Ley, Steven V.; Andrew Aquilina, J.; Robinson, Carol V.; Sharif, Isam; Gray, Gillian A.; Sabin, Caroline A.; Jenvey, Michelle C.; Kolstoe, Simon E.; Thompson, Darren; Wood, Stephen P.

2006-04-01

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

Cardiac Magnetic Resonance Imaging in Ischemic Heart Disease

PubMed Central

Florian, A.; Jurcut, R.; Ginghina, C.; Bogaert, J.

2011-01-01

Cardiac magnetic resonance imaging (MRI) has emerged as a prime player in the clinical and preclinical detection of ischemic heart disease (IHD) as well in the prognosis assessment by offering a comprehensive approach for all spectrums of coronary artery disease (CAD) patients. The aim of this review is to provide the reader a state–of–the art on how the newest cardiac MRI techniques can be used to study IHD patients. In patients with suspected/stable CAD, functional and perfusion imaging both at rest and during vasodilatatory stress (adenosine, dypiridamole)/dobutamine stress can accurately depict ischemic myocardium secondary to significant coronary artery stenosis. In patients with acute MI, MRI is a robust tool for differentiating and sizing the jeopardized and the infarcted myocardium by using a combination of functional, edema, perfusion and Gd contrast imaging. Moreover, important prognostic factors like myocardial salvage, the presence of microvascular obstruction (MVO), post reperfusion myocardial hemorrhage, RV involvement and infarct related complications can be assessed in the same examination. In patients with chronic ischemic cardiomyopathy, the role of the MRI extends from diagnosis by means of Gadolinium contrast scar imaging to therapy and prognosis by functional assessment and viability testing with rest and dobutamine stress imaging. In all the circumstances mentioned, MRI derived information has been proven valuable in every day clinical decision making and prognosis assessment. Thus, MRI is becoming more and more an accepted alternative to other imaging modalities both in the acute and chronic setting. PMID:22514564

Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair.

PubMed

Paul, Arghya; Hasan, Anwarul; Kindi, Hamood Al; Gaharwar, Akhilesh K; Rao, Vijayaraghava T S; Nikkhah, Mehdi; Shin, Su Ryon; Krafft, Dorothee; Dokmeci, Mehmet R; Shum-Tim, Dominique; Khademhosseini, Ali

2014-08-26

The objective of this study was to develop an injectable and biocompatible hydrogel which can efficiently deliver a nanocomplex of graphene oxide (GO) and vascular endothelial growth factor-165 (VEGF) pro-angiogenic gene for myocardial therapy. For the study, an efficient nonviral gene delivery system using polyethylenimine (PEI) functionalized GO nanosheets (fGO) complexed with DNAVEGF was formulated and incorporated in the low-modulus methacrylated gelatin (GelMA) hydrogel to promote controlled and localized gene therapy. It was hypothesized that the fGOVEGF/GelMA nanocomposite hydrogels can efficiently transfect myocardial tissues and induce favorable therapeutic effects without invoking cytotoxic effects. To evaluate this hypothesis, a rat model with acute myocardial infarction was used, and the therapeutic hydrogels were injected intramyocardially in the peri-infarct regions. The secreted VEGF from in vitro transfected cardiomyocytes demonstrated profound mitotic activities on endothelial cells. A significant increase in myocardial capillary density at the injected peri-infarct region and reduction in scar area were noted in the infarcted hearts with fGOVEGF/GelMA treatment compared to infarcted hearts treated with untreated sham, GelMA and DNAVEGF/GelMA groups. Furthermore, the fGOVEGF/GelMA group showed significantly higher (p < 0.05, n = 7) cardiac performance in echocardiography compared to other groups, 14 days postinjection. In addition, no significant differences were noticed between GO/GelMA and non-GO groups in the serum cytokine levels and quantitative PCR based inflammatory microRNA (miRNA) marker expressions at the injected sites. Collectively, the current findings suggest the feasibility of a combined hydrogel-based gene therapy system for ischemic heart diseases using nonviral hybrid complex of fGO and DNA.

Effectiveness of Autologous Fat Grafting in Adherent Scars: Results Obtained by a Comprehensive Scar Evaluation Protocol.

PubMed

Jaspers, Mariëlle E H; Brouwer, Katrien M; van Trier, Antoine J M; Groot, Marloes L; Middelkoop, Esther; van Zuijlen, Paul P M

2017-01-01

Nowadays, patients normally survive severe traumas such as burn injuries and necrotizing fasciitis. Large skin defects can be closed but the scars remain. Scars may become adherent to underlying structures when the subcutical fat layer is damaged. Autologous fat grafting provides the possibility of reconstructing a functional sliding layer underneath the scar. Autologous fat grafting is becoming increasingly popular for scar treatment, although large studies using validated evaluation tools are lacking. The authors therefore objectified the effectiveness of single-treatment autologous fat grafting on scar pliability using validated scar measurement tools. Forty patients with adherent scars receiving single-treatment autologous fat grafting were measured preoperatively and at 3-month follow-up. The primary outcome parameter was scar pliability, measured using the Cutometer. Scar quality was also evaluated by the Patient and Observer Scar Assessment Scale and the DSM II ColorMeter. To prevent selection bias, measurements were performed following a standardized algorithm. The Cutometer parameters elasticity and maximal extension improved 22.5 percent (p < 0.001) and 15.6 percent (p = 0.001), respectively. Total Patient and Observer Scar Assessment Scale scores improved from 3.6 to 2.9 on the observer scale, and from 5.1 to 3.8 on the patient scale (both p < 0.001). Color differences between the scar and normal skin remained unaltered. For the first time, the effect of autologous fat grafting on functional scar parameters was ascertained using a comprehensive scar evaluation protocol. The improved scar pliability supports the authors' hypothesis that the function of the subcutis can be restored to a certain extent by single-treatment autologous fat grafting. Therapeutic, IV.

Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction

PubMed Central

Projahn, Delia; Simsekyilmaz, Sakine; Singh, Smriti; Kanzler, Isabella; Kramp, Birgit K; Langer, Marcella; Burlacu, Alexandrina; Bernhagen, Jürgen; Klee, Doris; Zernecke, Alma; Hackeng, Tilman M; Groll, Jürgen; Weber, Christian; Liehn, Elisa A; Koenen, Rory R

2014-01-01

Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies. PMID:24512349

Clinical management of scar tissue.

PubMed

Kasch, M C

1988-01-01

This paper will review the physiology of scar formation including the properties of wound healing and scar remodeling. A clinical scar management program that includes evaluation of scar adhesions and use of a variety of therapy interventions to minimize the formation of scar will be described. Use of compression, massage, splints and functional activities is included in this program. The information is applicable for the general occupational therapist who sees patients with hand dysfunction as well as a therapist specializing in hand rehabilitation. Every therapist who treats hand trauma must be familiar with the sequence and the properties of scar formation in order to reestablish tendon gliding and facilitate early remodeling of scar tissue. Many treatment techniques can be directed toward scar adhesions and no one method is totally effective when used alone; used together, these techniques can positively influence scar formation and restore maximal hand function.

Paracrine Engineering of Human Explant-Derived Cardiac Stem Cells to Over-Express Stromal-Cell Derived Factor 1α Enhances Myocardial Repair.

PubMed

Tilokee, Everad L; Latham, Nicholas; Jackson, Robyn; Mayfield, Audrey E; Ye, Bin; Mount, Seth; Lam, Buu-Khanh; Suuronen, Erik J; Ruel, Marc; Stewart, Duncan J; Davis, Darryl R

2016-07-01

First generation cardiac stem cell products provide indirect cardiac repair but variably produce key cardioprotective cytokines, such as stromal-cell derived factor 1α, which opens the prospect of maximizing up-front paracrine-mediated repair. The mesenchymal subpopulation within explant derived human cardiac stem cells underwent lentiviral mediated gene transfer of stromal-cell derived factor 1α. Unlike previous unsuccessful attempts to increase efficacy by boosting the paracrine signature of cardiac stem cells, cytokine profiling revealed that stromal-cell derived factor 1α over-expression prevented lv-mediated "loss of cytokines" through autocrine stimulation of CXCR4+ cardiac stem cells. Stromal-cell derived factor 1α enhanced angiogenesis and stem cell recruitment while priming cardiac stem cells to readily adopt a cardiac identity. As compared to injection with unmodified cardiac stem cells, transplant of stromal-cell derived factor 1α enhanced cells into immunodeficient mice improved myocardial function and angiogenesis while reducing scarring. Increases in myocardial stromal-cell derived factor 1α content paralleled reductions in myocyte apoptosis but did not influence long-term engraftment or the fate of transplanted cells. Transplantation of stromal-cell derived factor 1α transduced cardiac stem cells increased the generation of new myocytes, recruitment of bone marrow cells, new myocyte/vessel formation and the salvage of reversibly damaged myocardium to enhance cardiac repair after experimental infarction. Stem Cells 2016;34:1826-1835. © 2016 AlphaMed Press.

High spatial resolution free-breathing 3D late gadolinium enhancement cardiac magnetic resonance imaging in ischaemic and non-ischaemic cardiomyopathy: quantitative assessment of scar mass and image quality.

PubMed

Bizino, Maurice B; Tao, Qian; Amersfoort, Jacob; Siebelink, Hans-Marc J; van den Bogaard, Pieter J; van der Geest, Rob J; Lamb, Hildo J

2018-04-06

To compare breath-hold (BH) with navigated free-breathing (FB) 3D late gadolinium enhancement cardiac MRI (LGE-CMR) MATERIALS AND METHODS: Fifty-one patients were retrospectively included (34 ischaemic cardiomyopathy, 14 non-ischaemic cardiomyopathy, three discarded). BH and FB 3D phase sensitive inversion recovery sequences were performed at 3T. FB datasets were reformatted into normal resolution (FB-NR, 1.46x1.46x10mm) and high resolution (FB-HR, isotropic 0.91-mm voxels). Scar mass, scar edge sharpness (SES), SNR and CNR were compared using paired-samples t-test, Pearson correlation and Bland-Altman analysis. Scar mass was similar in BH and FB-NR (mean ± SD: 15.5±18.0 g vs. 15.5±16.9 g, p=0.997), with good correlation (r=0.953), and no bias (mean difference ± SD: 0.00±5.47 g). FB-NR significantly overestimated scar mass compared with FB-HR (15.5±16.9 g vs 14.4±15.6 g; p=0.007). FB-NR and FB-HR correlated well (r=0.988), but Bland-Altman demonstrated systematic bias (1.15±2.84 g). SES was similar in BH and FB-NR (p=0.947), but significantly higher in FB-HR than FB-NR (p<0.01). SNR and CNR were lower in BH than FB-NR (p<0.01), and lower in FB-HR than FB-NR (p<0.01). Navigated free-breathing 3D LGE-CMR allows reliable scar mass quantification comparable to breath-hold. During free-breathing, spatial resolution can be increased resulting in improved sharpness and reduced scar mass. • Navigated free-breathing 3D late gadolinium enhancement is reliable for myocardial scar quantification. • High-resolution 3D late gadolinium enhancement increases scar sharpness • Ischaemic and non-ischaemic cardiomyopathy patients can be imaged using free-breathing LGE CMR.

[Stem cell therapy in cardiovascular diseases].

PubMed

Vértesaljai, Márton; Piróth, Zsolt; Fontos, Géza; Andréka, Gyórgy; Font, Gusztáv; Szánthó, Gergely; Réti, Marienn; Masszi, Tamás; Andréka, Peter

2005-11-20

Myocardial infarction is the leading cause of congestive heart failure in the industrialized world. Current treatments fail to address the underlying scarring and cell loss, which are the causes of ischaemic heart failure. Recent interest has focused on stem cells, which are undifferentiated and pluripotent cells that can proliferate, potentially self-renew, and differentiate into cardiomyocytes and endothelial cells. Myocardial regeneration is the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes were generated in what was previously considered a postmitotic organ. So far, candidates for cardiac stem cell therapy have been limited to patients with acute myocardial infarction and chronic ischaemic heart failure. Currently, bone marrow stem cells seem to be the most attractive cell type for these patients. The cells may be delivered by means of direct surgical injection, intracoronary infusion, retrograde venous infusion, and transendocardial infusion. Stem cells may directly increase cardiac contractility or passively limit infarct expansion and remodeling. Early phase I clinical studies indicate that stem cell transplantation is feasible and may have beneficial effects on ventricular remodeling after myocardial infarction. Future randomized clinical trials will establish the magnitude of benefit and the effect on mortality after stem cell therapy.

Cellular Encapsulation Enhances Cardiac Repair

PubMed Central

Levit, Rebecca D.; Landázuri, Natalia; Phelps, Edward A.; Brown, Milton E.; García, Andrés J.; Davis, Michael E.; Joseph, Giji; Long, Robert; Safley, Susan A.; Suever, Jonathan D.; Lyle, Alicia N.; Weber, Collin J.; Taylor, W. Robert

2013-01-01

Background Stem cells for cardiac repair have shown promise in preclinical trials, but lower than expected retention, viability, and efficacy. Encapsulation is one potential strategy to increase viable cell retention while facilitating paracrine effects. Methods and Results Human mesenchymal stem cells (hMSC) were encapsulated in alginate and attached to the heart with a hydrogel patch in a rat myocardial infarction (MI) model. Cells were tracked using bioluminescence (BLI) and cardiac function measured by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR). Microvasculature was quantified using von Willebrand factor staining and scar measured by Masson's Trichrome. Post‐MI ejection fraction by CMR was greatly improved in encapsulated hMSC‐treated animals (MI: 34±3%, MI+Gel: 35±3%, MI+Gel+hMSC: 39±2%, MI+Gel+encapsulated hMSC: 56±1%; n=4 per group; P<0.01). Data represent mean±SEM. By TTE, encapsulated hMSC‐treated animals had improved fractional shortening. Longitudinal BLI showed greatest hMSC retention when the cells were encapsulated (P<0.05). Scar size at 28 days was significantly reduced in encapsulated hMSC‐treated animals (MI: 12±1%, n=8; MI+Gel: 14±2%, n=7; MI+Gel+hMSC: 14±1%, n=7; MI+Gel+encapsulated hMSC: 7±1%, n=6; P<0.05). There was a large increase in microvascular density in the peri‐infarct area (MI: 121±10, n=7; MI+Gel: 153±26, n=5; MI+Gel+hMSC: 198±18, n=7; MI+Gel+encapsulated hMSC: 828±56 vessels/mm2, n=6; P<0.01). Conclusions Alginate encapsulation improved retention of hMSCs and facilitated paracrine effects such as increased peri‐infarct microvasculature and decreased scar. Encapsulation of MSCs improved cardiac function post‐MI and represents a new, translatable strategy for optimization of regenerative therapies for cardiovascular diseases. PMID:24113327

Prospective Evaluation of 18F-Fluorodeoxyglucose Uptake in Postischemic Myocardium by Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging as a Prognostic Marker of Functional Outcome.

PubMed

Rischpler, Christoph; Dirschinger, Ralf J; Nekolla, Stephan G; Kossmann, Hans; Nicolosi, Stefania; Hanus, Franziska; van Marwick, Sandra; Kunze, Karl P; Meinicke, Alexander; Götze, Katharina; Kastrati, Adnan; Langwieser, Nicolas; Ibrahim, Tareq; Nahrendorf, Matthias; Schwaiger, Markus; Laugwitz, Karl-Ludwig

2016-04-01

The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI (18)F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of (18)F-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed (18)F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, (99m)Tc-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of (18)F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that (18)F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14(high)/CD16(+) monocytes correlated with the infarction size and (18)F-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). (18)F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake valuemean was associated with left ventricular functional outcome independent of infarct size (Δ ejection fraction: P<0.04, Δ end-diastolic volume: P<0.02, Δ end-systolic volume: P<0.005). In this study, the intensity of (18)F-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, (18)F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. © 2016 American Heart Association, Inc.

Sertoli cell androgen receptor expression regulates temporal fetal and adult Leydig cell differentiation, function, and population size.

PubMed

Hazra, Rasmani; Jimenez, Mark; Desai, Reena; Handelsman, David J; Allan, Charles M

2013-09-01

We recently created a mouse model displaying precocious Sertoli cell (SC) and spermatogenic development induced by SC-specific transgenic androgen receptor expression (TgSCAR). Here we reveal that TgSCAR regulates the development, function, and absolute number of Leydig cells (LCs). Total fetal and adult type LC numbers were reduced in postnatal and adult TgSCAR vs control testes, despite normal circulating LH levels. Normal LC to SC ratios found in TgSCAR testes indicate that SC androgen receptor (SCAR)-mediated activity confers a quorum-dependent relationship between total SC and LC numbers. TgSCAR enhanced LC differentiation, shown by elevated ratios of advanced to immature LC types, and reduced LC proliferation in postnatal TgSCAR vs control testes. Postnatal TgSCAR testes displayed up-regulated expression of coupled ligand-receptor transcripts (Amh-Amhr2, Dhh-Ptch1, Pdgfa-Pdgfra) for potential SCAR-stimulated paracrine pathways, which may coordinate LC differentiation. Neonatal TgSCAR testes displayed normal T and dihydrotestosterone levels despite differential changes to steroidogenic gene expression, with down-regulated Star, Cyp11a1, and Cyp17a1 expression contrasting with up-regulated Hsd3b1, Hsd17b3, and Srd5a1 expression. TgSCAR males also displayed elevated postnatal and normal adult serum testosterone levels, despite reduced LC numbers. Enhanced adult-type LC steroidogenic output was revealed by increased pubertal testicular T, dihydrotestosterone, 3α-diol and 3β-diol levels per LC and up-regulated steroidogenic gene (Nr5a1, Lhr, Cyp11a1, Cyp17a1, Hsd3b6, Srd5a1) expression in pubertal or adult TgSCAR vs control males, suggesting regulatory mechanisms maintain androgen levels independently of absolute LC numbers. Our unique gain-of-function TgSCAR model has revealed that SCAR activity controls temporal LC differentiation, steroidogenic function, and population size.

Pathogenesis of Arrhythmogenic Cardiomyopathy

PubMed Central

Asimaki, Angeliki; Kleber, Andre G.; Saffitz, Jeffrey E.

2015-01-01

Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease. It is characterized by frequent ventricular arrhythmias and increased risk of sudden cardiac death typically arising as an early manifestation before the onset of significant myocardial remodeling. Myocardial degeneration, often confined to the right ventricular free wall, with replacement by fibrofatty scar tissue, develops in many patients. ACM is a familial disease but genetic penetrance can be low and disease expression is highly variable. Inflammation may promote disease progression. It also appears that exercise increases disease penetrance and accelerates its development. More than 60% of probands harbor mutations in genes encoding desmosomal proteins, which has raised the possibility that defective cell-cell adhesion may play a role in disease pathogenesis. Recent advances have implicated changes in the canonical Wnt/β-catenin and Hippo signaling pathways and defects in forwarding trafficking of ion channels and other proteins to the intercalated disk in cardiac myocytes. This review summarizes current understanding of the pathogenesis of ACM and highlights future research directions. PMID:26199027

Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosenpud, J.D.; Montanaro, A.; Hart, M.V.

1984-08-01

Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment,more » major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.« less

Gene Therapy With Angiotensin-(1-9) Preserves Left Ventricular Systolic Function After Myocardial Infarction.

PubMed

Fattah, Caroline; Nather, Katrin; McCarroll, Charlotte S; Hortigon-Vinagre, Maria P; Zamora, Victor; Flores-Munoz, Monica; McArthur, Lisa; Zentilin, Lorena; Giacca, Mauro; Touyz, Rhian M; Smith, Godfrey L; Loughrey, Christopher M; Nicklin, Stuart A

2016-12-20

Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin-angiotensin-aldosterone system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic mini-pump. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). The authors evaluated effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post-infarction. C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular pressure volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation/contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff-perfused whole-heart model. Gene delivery of Ang-(1-9) reduced sudden cardiac death post-MI. Pressure volume measurements revealed complete restoration of end-systolic pressure, ejection fraction, end-systolic volume, and the end-diastolic pressure volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. Our novel findings showed that Ang-(1-9) gene therapy preserved left ventricular systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) directly affected cardiomyocyte calcium handling through a protein kinase A-dependent mechanism. These data emphasized Ang-(1-9) gene therapy as a potential new strategy in the context of MI. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Myocardial scar location as detected by cardiac magnetic resonance is associated with the outcome in heart failure patients undergoing surgical ventricular reconstruction.

PubMed

Castelvecchio, Serenella; Careri, Giulia; Ambrogi, Federico; Camporeale, Antonia; Menicanti, Lorenzo; Secchi, Francesco; Lombardi, Massimo

2018-01-01

Post-infarction myocardial scar causes adverse left ventricular remodelling and negatively affects the prognosis. We sought to investigate whether scar extent and location obtained by cardiac magnetic resonance may affect the reverse remodelling and survival of heart failure patients undergoing surgical ventricular reconstruction. From January 2011 to December 2015, 151 consecutive patients with previous myocardial infarction and left ventricular remodelling underwent surgical ventricular reconstruction at our Institution, of which 88 (58%) patients had a preoperative protocol-standardized late gadolinium enhancement (LGE)-cardiac magnetic resonance examination during the week before surgery. We excluded 40 patients with devices (26%), 15 patients with irregular heart rhythm (permanent atrial fibrillation, 10% not included in the device group) or mixed contraindications (severe claustrophobia or presence of material magnetic resonance not compatible). Among the 145 survivors, 11 patients received an implantable cardioverter defibrillator after surgery (mostly for persistent low ejection fraction) and were excluded as well, yielding a total of 59 patients (48 men, aged 65 ± 9 years) who repeated a protocol-standardized LGE-cardiac magnetic resonance examination even 6 months postoperatively and therefore represent the study population. Patients were grouped according to the presence of LGE in the antero-basal left ventricular segments (Group A) or the absence of LGE in the same segments (Group B). The postoperative left ventricular end-systolic volume index was considered the primary end-point. After surgery, left ventricular end-systolic volume index and end-diastolic volume index significantly decreased (P < 0.001, for both), while diastolic sphericity index and ejection fraction significantly increased (P = 0.015 and P < 0.001, respectively). The presence of LGE in the antero-basal left ventricular segments (10 patients, Group A) was the only independent predictor of outcome (P = 0.02) at multivariate analysis, being the postoperative left ventricular end-systolic volume index significantly higher compared to that of patients of Group B (49 patients) (78 ± 26 ml/m2 vs 55 ± 20 ml/m2, P = 0.003). Furthermore, patients with a postoperative left ventricular end-systolic volume index >60 ml/m2 showed a higher risk of cardiac events (hazard ratio = 3.67, P = 0.02). In patients undergoing surgical ventricular reconstruction, LGE scar location affects the left ventricular reverse remodelling, which in turn might limit the survival benefit. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Epigenetic regulation of cardiac fibrosis

PubMed Central

Stratton, Matthew S.; McKinsey, Timothy A.

2016-01-01

Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative, replacing areas of myocyte loss with a structural scar following infarction, or reactive, which is triggered in the absence of cell death and involves interstitial ECM deposition in response to long-lasting stress. Interstitial fibrosis can increase the passive stiffness of the myocardium, resulting in impaired relaxation and diastolic dysfunction. Additionally, fibrosis can lead to disruption of electrical conduction in the heart, causing arrhythmias, and can limit myocyte oxygen availability and thus exacerbate myocardial ischemia. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of small molecules that target epigenetic regulators as a means of treating fibrotic cardiac diseases. PMID:26876451

Calpastatin overexpression impairs postinfarct scar healing in mice by compromising reparative immune cell recruitment and activation.

PubMed

Wan, Feng; Letavernier, Emmanuel; Le Saux, Claude Jourdan; Houssaini, Amal; Abid, Shariq; Czibik, Gabor; Sawaki, Daigo; Marcos, Elisabeth; Dubois-Rande, Jean-Luc; Baud, Laurent; Adnot, Serge; Derumeaux, Geneviève; Gellen, Barnabas

2015-12-01

The activation of the calpain system is involved in the repair process following myocardial infarction (MI). However, the impact of the inhibition of calpain by calpastatin, its natural inhibitor, on scar healing and left ventricular (LV) remodeling is elusive. Male mice ubiquitously overexpressing calpastatin (TG) and wild-type (WT) controls were subjected to an anterior coronary artery ligation. Mortality at 6 wk was higher in TG mice (24% in WT vs. 44% in TG, P < 0.05) driven by a significantly higher incidence of cardiac rupture during the first week post-MI, despite comparable infarct size and LV dysfunction and dilatation. Calpain activation post-MI was blunted in TG myocardium. In TG mice, inflammatory cell infiltration and activation were reduced in the infarct zone (IZ), particularly affecting M2 macrophages and CD4(+) T cells, which are crucial for scar healing. To elucidate the role of calpastatin overexpression in macrophages, we stimulated peritoneal macrophages obtained from TG and WT mice in vitro with IL-4, yielding an abrogated M2 polarization in TG but not in WT cells. Lymphopenic Rag1(-/-) mice receiving TG splenocytes before MI demonstrated decreased T-cell recruitment and M2 macrophage activation in the IZ day 5 after MI compared with those receiving WT splenocytes. Calpastatin overexpression prevented the activation of the calpain system after MI. It also impaired scar healing, promoted LV rupture, and increased mortality. Defective scar formation was associated with blunted CD4(+) T-cell and M2-macrophage recruitment. Copyright © 2015 the American Physiological Society.

Increased Regional Epicardial Fat Volume Associated with Reversible Myocardial Ischemia in Patients with Suspected Coronary Artery Disease

PubMed Central

Khawaja, Tuba; Greer, Christine; Thadani, Samir R.; Kato, Tomoko S.; Bhatia, Ketan; Shimbo, Daichi; Konkak, Andrew; Bokhari, Sabahat; Einstein, Andrew J.; Schulze, P. Christian

2015-01-01

Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm3, 156.4 ± 121.9 cm3, and 96.3 ± 102.1 cm3, respectively (P < 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm3; P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm3; P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease. PMID:25339129

[Burn scars].

PubMed

Roques, Claude

2013-01-01

Burns often result in extensive scars which can change the body aesthetically and/ or functionally. Rapid scarring is a sign of a good prognosis. Preventative actions such as hydration, compression, massage, posture and splints help to prevent or contain the negative evolution of pathological scars.

Positive tuberculin skin tests in nursing home residents in Southern Taiwan.

PubMed

Chang, Chia-Ming; Lee, Nan-Yao; Lee, Hsin-Chun; Wu, Chi-Jung; Chen, Po-Lin; Lee, Ching-Chi; Shih, Hsin-I; Ko, Wen-Chien

2010-01-01

In Taiwan, the tuberculin skin test (TST) is not recommended as a screening test for Mycobacterium tuberculosis (TB) infections. The aim of this study is to determine the prevalence and predictors of positive tuberculin reactivity and its association with TB infections among nursing home residents in Taiwan. A cross-sectional study and review of medical records were conducted at four nursing homes in Tainan City. A one-stage TST was performed by study nurses using two tuberculin units of purified protein derivative (PPD) of the RT23 strain. An induration ≥10 mm at 72 h was considered to be a positive reaction. Chest radiographs, acid-fast stains and mycobacterial cultures of three sputum samples were performed for those with a positive TST result. Of 115 residents (66.5% participation, mean age 73.1 years) who underwent a TST, 26 (22.6%) had a positive reaction. One woman was microbiologically diagnosed to have pulmonary TB. On multivariate analysis, a Bacille Calmette-Guérin (BCG) scar and a history of myocardial infarction were significantly associated with a positive TST. In conclusions, this study shows a considerable rate of positive TST among nursing home residents in southern Taiwan. A BCG scar and a history of myocardial infarction were associated with a positive TST. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating

PubMed Central

Engler, Adam J.; Carag-Krieger, Christine; Johnson, Colin P.; Raab, Matthew; Tang, Hsin-Yao; Speicher, David W.; Sanger, Joseph W.; Sanger, Jean M.; Discher, Dennis E.

2009-01-01

Summary Fibrotic rigidification following a myocardial infarct is known to impair cardiac output, and it is also known that cardiomyocytes on rigid culture substrates show a progressive loss of rhythmic beating. Here, isolated embryonic cardiomyocytes cultured on a series of flexible substrates show that matrices that mimic the elasticity of the developing myocardial microenvironment are optimal for transmitting contractile work to the matrix and for promoting actomyosin striation and 1-Hz beating. On hard matrices that mechanically mimic a post-infarct fibrotic scar, cells overstrain themselves, lack striated myofibrils and stop beating; on very soft matrices, cells preserve contractile beating for days in culture but do very little work. Optimal matrix leads to a strain match between cell and matrix, and suggests dynamic differences in intracellular protein structures. A ‘cysteine shotgun’ method of labeling the in situ proteome reveals differences in assembly or conformation of several abundant cytoskeletal proteins, including vimentin, filamin and myosin. Combined with recent results, which show that stem cell differentiation is also highly sensitive to matrix elasticity, the methods and analyses might be useful in the culture and assessment of cardiogenesis of both embryonic stem cells and induced pluripotent stem cells. The results described here also highlight the need for greater attention to fibrosis and mechanical microenvironments in cell therapy and development. PMID:18957515

Efficacy of IPL device combined with intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with regards to the recovery of skin barrier function: A pilot study.

PubMed

Kim, Dong Young; Park, Hyun Sun; Yoon, Hyun-Sun; Cho, Soyun

2015-10-01

Keloids and hypertrophic scars are prevalent and psychologically distressful dermatologic conditions. Various treatment modalities have been tried but without complete success by any one method. We evaluated the efficacy of a combination of intense pulsed light (IPL) device and intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with respect to the recovery of skin barrier function. Totally 52 Korean patients were treated by the combined treatment at 4-8-week intervals. Using digital photographs, changes in scar appearance were assessed with modified Vancouver Scar Scale (MVSS), physicians' global assessment (PGA) and patient's satisfaction score. In 12 patients, the stratum corneum (SC) barrier function was assessed by measuring transepidermal water loss (TEWL) and SC capacitance. Most scars demonstrated significant clinical improvement in MVSS, PGA and patient's satisfaction score after the combined therapy. A significant decrease of TEWL and elevation of SC capacitance were also documented after the treatment. The combination therapy (IPL + corticosteroid injection) not only improves the appearance of keloids and hypertrophic scars but also increases the recovery level of skin hydration status in terms of the skin barrier function.

Transmyocardial laser revascularization in the acute ischaemic heart: no improvement of acute myocardial perfusion or prevention of myocardial infarction.

PubMed

Eckstein, F S; Scheule, A M; Vogel, U; Schmid, S T; Miller, S; Jurmann, M J; Ziemer, G

1999-05-01

Transmyocardial laser revascularization (TMLR) has been used to provide enhanced myocardial perfusion in patients not suitable for coronary revascularization or angioplasty. This study investigates the acute changes in myocardial perfusion after TMLR with a Holmium:Yttrium-Aluminium-Garnet (YAG) laser with a thermal imaging camera in a model of acute ischaemia, and confirms its midterm effects by post-mortem investigation of magnetic resonance imaging and histopathological examination. Acute myocardial ischaemia was induced by occlusion of the dominant diagonal branch in ten sheep. Perfusion measurements were undertaken first in the unaffected myocardium, then after temporary occlusion of the coronary to obtain a control measurement for ischaemic myocardium. Myocardial perfusion was then evaluated during reperfusion after release of coronary occlusion. Then the coronary was permanently occluded and 20.5+/-2 channels were drilled with the Holmium:YAG laser and perfusion was measured again. The other four sheep served as control with untreated ischaemia. All animals were sacrificed after 28 days following administration of gadolinium i.v. to serve as contrast medium for magnetic resonance tomography. The hearts were subjected to magnetic resonance tomography and histopathological examination. Intraoperative perfusion measurements revealed a decreased perfusion after temporary occlusion and an increased perfusion in reperfused myocardium. After TMLR, no improvement of myocardial perfusion above the ischaemic level could be shown. Magnetic resonance images could neither confirm patent laser channels nor viable myocardium within ischaemic areas. On histology no patent endocardial laser channel could be detected. The transmural features were myocardial infarct with scar tissue. In the presented sheep model with acute ischaemia, TMLR with a Holmium:YAG laser did not provide acute improvement of myocardial perfusion as assessed by a thermal imaging camera. This would suggest no direct contribution of newly created laser channels to myocardial perfusion. As chronic effects are concerned, no perfused laser channels could be identified by later magnetic resonance imaging or histology.

Scar prevention and remodeling: a review of the medical, surgical, topical and light treatment approaches.

PubMed

Kerwin, Leonard Y; El Tal, Abdel Kader; Stiff, Mark A; Fakhouri, Tarek M

2014-08-01

Cosmetic, functional, and structural sequelae of scarring are innumerable, and measures exist to optimize and ultimately minimize these sequelae. To evaluate the innumerable methods available to decrease the cosmetic, functional, and structural repercussions of scarring, pubMed search of the English literature with key words scar, scar revision, scar prevention, scar treatment, scar remodeling, cicatrix, cicatrix treatment, and cicatrix remodeling was done. Original articles and reviews were examined and included. Seventy-nine manuscripts were reviewed. Techniques, comparisons, and results were reviewed and tabulated. Overall, though topical modalities are easier to use and are usually more attractive to the patient, the surgical approaches still prove to be superior and more reliable. However, advances in topical medications for scar modification are on the rise and a change towards medical treatment of scars may emerge as the next best approach. Comparison studies of the innumerable specific modalities for scar revision and prevention are impossible. Standardization of techniques is lacking. Scarring, the body's natural response to a wound, can create many adverse effects. At this point, the practice of sound, surgical fundamentals still trump the most advanced preventative methods and revision techniques. Advances in medical approaches are available, however, to assist the scarring process, which even the most advanced surgical fundamentals will ultimately lead to. Whether through newer topical therapies, light treatment, or classical surgical intervention, our treatment armamentarium of scars has expanded and will allow us to maximize scar prevention and to minimize scar morbidity. © 2014 The International Society of Dermatology.

Positron emission tomography for the assessment of myocardial viability: an evidence-based analysis.

PubMed

2010-01-01

In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography.A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed.The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlPOSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based AnalysisMAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based Analysis The objective of this analysis is to assess the effectiveness and safety of positron emission tomography (PET) imaging using F-18-fluorodeoxyglucose (FDG) for the assessment of myocardial viability. To evaluate the effectiveness of FDG PET viability imaging, the following outcomes are examined: the diagnostic accuracy of FDG PET for predicting functional recovery;the impact of PET viability imaging on prognosis (mortality and other patient outcomes); andthe contribution of PET viability imaging to treatment decision making and subsequent patient outcomes. CONDITION AND TARGET POPULATION LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AND HEART FAILURE: Heart failure is a complex syndrome characterized by the heart's inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. IN GENERAL, THERE ARE THREE OPTIONS FOR THE TREATMENT OF HEART FAILURE: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure. Left ventricular dysfunction may be permanent if a myocardial scar is formed, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically: dobutamine echocardiography (echo),stress echo with contrast,SPECT using either technetium or thallium,cardiac magnetic resonance imaging (cardiac MRI), andpositron emission tomography (PET). Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 - 10 μg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT: SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery. Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. (ABSTRACT TRUNCATED)

Successful Nd:Yag Laser Photocoagulation Of Arrhythmogenic Myocardium: Potential Limitations Of Current Optical Delivery Systems.

NASA Astrophysics Data System (ADS)

Svenson, Robert H.; Marroum, Marie-Claire; Frank, Frank; Selle, Jay G.; Gallagher, John J.; Bou-Saba, George; Seifert, Kathleen T.; Linder, Kathy; Tatsis, George P.

1987-04-01

Canine myocardial lesions of predictable dimensions can be achieved with Nd:YAG laser photocoagulation. These lesions are well demarcated from surrounding normal tissue and heal with homogeneous scar formation. Intraoperative Nd:YAG laser photocoagulation successfully ablated 52 of 55 ventricular tachycardias in 17 patients. Histologic examination of tissues from these arrhythmogenic areas showed differences from lesions produced on canine epicardium. Lesions from the human cases were less predictable and not well circumscribed. These differences are felt to be due to optical inhomogeneities present in diseased, scarred human myocardium, geometric irregularities of the endocardial surface, anatomical constraints on tissue-fiber distance, and the angle of incidence of the beam with the tissue. Modifications of current delivery systems may overcome some of these limitations. Ablation of ventricular tachycardia arising deeper than 4.0 to 6.0 mm. from the irradiated surface may require interstitial probes coupled to the fiberoptic.

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

PubMed Central

Xue, Meilang; Jackson, Christopher J.

2015-01-01

Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation. PMID:25785236

Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tellier, P.; Paycha, F.; Antony, I.

1988-08-01

In order to clarify the significance of anginal pain and myocardial thallium-201 scan defects in cardiac sarcoidosis, the pharmacologic effect of dipyridamole on myocardial perfusion was assessed by planar thallium-201 myocardial scintigraphy in patients with sarcoidosis. Thallium-201 myocardial scintigraphy was performed at rest and after 0.56 mg/kg intravenous dipyridamole during four minutes in 16 patients with sarcoidosis. The myocardial scan (45-degree and 70-degree left anterior oblique, and anterior views) was divided into 15 segments. Results were evaluated by the number of segmental defects and with a global perfusion score (from 0 to 60) by a semi-quantitative index depending on themore » size and severity of myocardial thallium-201 defects. Thirteen of the 16 patients showed partial or total reversion of their thallium-201 defects on redistribution scanning either at rest or after dipyridamole. The mean (+/- SD) number of myocardial perfusion defects that were present in all the patients decreased from 5.31 +/- 1.78 at rest to 3.25 +/- 2.52 after redistribution (p less than 0.001) and to 2.19 +/- 2.10 after dipyridamole (p less than 0.001). The mean global perfusion score increased from 53.2 +/- 3.0 at rest to 56.2 +/- 2.9 after redistribution (p less than 0.001) and to 57.2 +/- 2.7 after dipyridamole (p less than 0.001). A significant correlation (r = 0.82, p less than 0.001) was found between the increase of global perfusion score on redistribution and after dipyridamole. The reversibility of myocardial scan defects is a common finding in sarcoidosis. It makes unlikely the role of scar fibrosis or extensive confluent granulomas as a mechanism for such defects. The effect of dipyridamole suggests the presence of reversible disorders lying at the coronary microvascular level.« less

The Living Scar – Cardiac Fibroblasts and the Injured Heart

PubMed Central

Rog-Zielinska, Eva A; Norris, Russell A; Kohl, Peter; Markwald, Roger

2015-01-01

Cardiac scars, often perceived as “dead” tissue, are very much alive, with heterocellular activity ensuring the maintenance of structural and mechanical integrity following heart injury. To form a scar, non-myocytes such as fibroblasts, proliferate and are recruited from intra- and extra-cardiac sources. Fibroblasts perform important autocrine and paracrine signalling functions. They also establish mechanical and, as is increasingly evident, electrical junctions with other cells. While fibroblasts were previously thought to act simply as electrical insulators, they may be electrically connected among themselves and, under certain circumstances, to other cells, including cardiomyocytes. A better understanding of these interactions will help target scar structure and function and facilitate the development of novel therapies aimed at modifying scar properties for patient benefit. This review explores available insight and recent concepts on fibroblast integration in the heart, and highlights potential avenues for harnessing their roles to optimise scar function following heart injury such as infarction, and therapeutic interventions such as ablation. PMID:26776094

QRS-fragmentation: Case report and review of the literature.

PubMed

Illescas-González, Edgar; Araiza-Garaygordobil, Diego; Sierra Lara, Jorge Daniel; Ramirez-Salazar, Aristoteles; Sierra-Fernández, Carlos; Alexanderson-Rosas, Erick

Fragmentation of QRS complex (QRSf) is an easily evaluable, non-invasive electrocardiographic parameter that represents depolarisation anomalies and has been associated with several adverse outcomes, such as sudden death, fibrosis, arrhythmic burden, and a worse prognosis in different conditions, including coronary artery disease (CAD). The case is presented of a 69-year old male referred due to symptoms of chronic stable angina. His electrocardiogram showed sinus rhythm, absence of Q waves, but the presence of QRSf in the inferior leads and V4-V6. A Tc-99 myocardial perfusion SPECT scan revealed a fixed perfusion defect in the inferolateral region, corresponding to the finding of QRSf. QRSf is an easily valuable electrocardiographic marker with relative sensitivity, but poor specificity. Its routine clinical application could contribute to an increase in the suspicion of coronary artery disease. The presence of fragmented QRS represents distortion of signal conduction and depolarisation, which is related to myocardial scar or myocardial fibrosis. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Patient experiences of burn scars in adults and children and development of a health-related quality of life conceptual model: A qualitative study.

PubMed

Simons, Megan; Price, Nathaniel; Kimble, Roy; Tyack, Zephanie

2016-05-01

The aim of this study was to understand the impact of burn scars on health-related quality of life (HRQOL) from the perspective of adults and children with burn scars, and caregivers to inform the development of a conceptual model of burn scar HRQOL. Twenty-one participants (adults and children) with burn scars and nine caregivers participated in semi-structured, face-to-face interviews between 2012 and 2013. During the interviews, participants were asked to describe features about their (or their child's) burn scars and its impact on everyday life. Two coders conducted thematic analysis, with consensus achieved through discussion and review with a third coder. The literature on HRQOL models was then reviewed to further inform the development of a conceptual model of burn scar HRQOL. Five themes emerged from the qualitative data: 'physical and sensory symptoms', 'impact of burn scar interventions', 'impact of burn scar symptoms', 'personal factors' and 'change over time'. Caregivers offered further insights into family functioning after burn, and the impacts of burn scars and burn scar interventions on family life. In the conceptual model, symptoms (sensory and physical) of burn scars are considered proximal to HRQOL, with distal indicators including functioning (physical, emotional, social, cognitive), individual factors and the environment. Overall quality of life was affected by HRQOL. Understanding the impact of burn scars on HRQOL and the development of a conceptual model will inform future burn scar research and clinical practice. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

The transcription factor GATA4 promotes myocardial regeneration in neonatal mice.

PubMed

Malek Mohammadi, Mona; Kattih, Badder; Grund, Andrea; Froese, Natali; Korf-Klingebiel, Mortimer; Gigina, Anna; Schrameck, Ulrike; Rudat, Carsten; Liang, Qiangrong; Kispert, Andreas; Wollert, Kai C; Bauersachs, Johann; Heineke, Joerg

2017-02-01

Heart failure is often the consequence of insufficient cardiac regeneration. Neonatal mice retain a certain capability of myocardial regeneration until postnatal day (P)7, although the underlying transcriptional mechanisms remain largely unknown. We demonstrate here that cardiac abundance of the transcription factor GATA4 was high at P1, but became strongly reduced at P7 in parallel with loss of regenerative capacity. Reconstitution of cardiac GATA4 levels by adenoviral gene transfer markedly improved cardiac regeneration after cryoinjury at P7. In contrast, the myocardial scar was larger in cardiomyocyte-specific Gata4 knockout (CM-G4-KO) mice after cryoinjury at P0, indicative of impaired regeneration, which was accompanied by reduced cardiomyocyte proliferation and reduced myocardial angiogenesis in CM-G4-KO mice. Cardiomyocyte proliferation was also diminished in cardiac explants from CM-G4-KO mice and in isolated cardiomyocytes with reduced GATA4 expression. Mechanistically, decreased GATA4 levels caused the downregulation of several pro-regenerative genes (among them interleukin-13, Il13) in the myocardium. Interestingly, systemic administration of IL-13 rescued defective heart regeneration in CM-G4-KO mice and could be evaluated as therapeutic strategy in the future. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Area at risk can be assessed by iodine-123-meta-iodobenzylguanidine single-photon emission computed tomography after myocardial infarction: a prospective study.

PubMed

Hedon, Christophe; Huet, Fabien; Ben Bouallegue, Fayçal; Vernhet, Hélène; Macia, Jean-Christophe; Cung, Thien-Tri; Leclercq, Florence; Cade, Stéphane; Cransac, Frédéric; Lattuca, Benoit; Vandenberghe, D'Arcy; Bourdon, Aurélie; Benkiran, Meriem; Vauchot, Fabien; Gervasoni, Richard; D'estanque, Emmanuel; Mariano-Goulart, Denis; Roubille, François

2018-02-01

Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard). A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment. I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P<0.0001). CMR and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002). Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable myocardium) was significantly higher than by CMR (P=0.02). In patients with STEMI, I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

Potential Applications of PET/MR Imaging in Cardiology.

PubMed

Ratib, Osman; Nkoulou, René

2014-06-01

Recent advances in hybrid PET/MR imaging have opened new perspectives for cardiovascular applications. Although cardiac MR imaging has gained wider adoption for routine clinical applications, PET images remain the reference in many applications for which objective analysis of metabolic and physiologic parameters is needed. In particular, in cardiovascular diseases-more specifically, coronary artery disease-the use of quantitative and measurable parameters in a reproducible way is essential for the management of therapeutic decisions and patient follow-up. Functional MR images and dynamic assessment of myocardial perfusion from transit of intravascular contrast medium can provide useful criteria for identifying areas of decreased myocardial perfusion or for assessing tissue viability from late contrast enhancement of scar tissue. PET images, however, will provide more quantitative data on true tissue perfusion and metabolism. Quantitative myocardial flow can also lead to accurate assessment of coronary flow reserve. The combination of both modalities will therefore provide complementary data that can be expected to improve the accuracy and reproducibility of diagnostic procedures. But the true potential of hybrid PET/MR imaging may reside in applications beyond the domain of coronary artery disease. The combination of both modalities in assessment of other cardiac diseases such as inflammation and of other systemic diseases can also be envisioned. It is also predicted that the 2 modalities combined could help characterize atherosclerotic plaques and differentiate plaques with a high risk of rupture from stable plaques. In the future, the development of new tracers will also open new perspectives in evaluating myocardial remodeling and in assessing the kinetics of stem cell therapy in myocardial infarction. New tracers will also provide new means for evaluating alterations in cardiac innervation, angiogenesis, and even the assessment of reporter gene technologies. The fusion of 2 potentially competing modalities can certainly offer the best of each modality in a single procedure. The impact of such advanced technology in routine clinical practice will still need to be demonstrated. Beyond the expected improvement in patient management and the potential impact on patient outcome, PET/MR imaging will also need to establish its medicoeconomic justification in an era of health-care economic restrictions. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Prophylactic Catheter Ablation for the Prevention of Defibrillator Therapy

PubMed Central

Reddy, Vivek Y.; Reynolds, Matthew R.; Neuzil, Petr; Richardson, Allison W.; Taborsky, Milos; Jongnarangsin, Krit; Kralovec, Stepan; Sediva, Lucie; Ruskin, Jeremy N.; Josephson, Mark E.

2008-01-01

BACKGROUND For patients who have a ventricular tachyarrhythmic event, implantable cardioverter–defibrillators (ICDs) are a mainstay of therapy to prevent sudden death. However, ICD shocks are painful, can result in clinical depression, and do not offer complete protection against death from arrhythmia. We designed this randomized trial to examine whether prophylactic radiofrequency catheter ablation of arrhythmogenic ventricular tissue would reduce the incidence of ICD therapy. METHODS Eligible patients with a history of a myocardial infarction underwent defibrillator implantation for spontaneous ventricular tachycardia or fibrillation. The patients did not receive antiarrhythmic drugs. Patients were randomly assigned to defibrillator implantation alone or defibrillator implantation with adjunctive catheter ablation (64 patients in each group). Ablation was performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm. The primary end point was survival free from any appropriate ICD therapy. RESULTS The mortality rate 30 days after ablation was zero, and there were no significant changes in ventricular function or functional class during the mean (±SD) follow-up period of 22.5±5.5 months. Twenty-one patients assigned to defibrillator implantation alone (33%) and eight patients assigned to defibrillator implantation plus ablation (12%) received appropriate ICD therapy (antitachycardia pacing or shocks) (hazard ratio in the ablation group, 0.35; 95% confidence interval, 0.15 to 0.78, P = 0.007). Among these patients, 20 in the control group (31%) and 6 in the ablation group (9%) received shocks (P = 0.003). Mortality was not increased in the group assigned to ablation as compared with the control group (9% vs. 17%, P = 0.29). CONCLUSIONS In this randomized trial, prophylactic substrate-based catheter ablation reduced the incidence of ICD therapy in patients with a history of myocardial infarction who received ICDs for the secondary prevention of sudden death. (Current Controlled Trials number, ISRCTN62488166.) PMID:18160685

Implementation of a burn scar assessment system by ultrasound techniques.

PubMed

Du, Yi-Chun; Lin, Chih-Ming; Chen, Yung-Fu; Chen, Chung-Lin; Chen, Tainsong

2006-01-01

Tissue injury and its ensuing healing process cause scar formation. In addition to physical disability, the subsequent disfigurements from burns often bring negative psychological impacts on the survivors. Scar hypertrophy and contracture limit the joint motion and body function of the patient. With fast development of the current available technologies regarding the scar therapies, not only the process of wound healing has to be focused, but also the cosmetic and functional outcomes need to be emphasized. Therefore, proper evaluation and assessment of the healing process to nil scar status is highly recommended. However, the currently employed tools for scar evaluation are mostly subjective. For example, Vancouver General Hospital (VGH) scar index uses color, pigmentation, vascularity, pliability, and depth of the scar as dependent variables for scar evaluation. These parameters only estimate the superficial surface of the scar, but they can not evaluate the deeper tissue within dermis. Ultrasound is a safe, inexpensive, and multifunctional technique for probing tissue characteristics. In addition, its resolution is not inferior to other measurement techniques. Although 3D-ultrasound is available in clinical application, it's still not widely used in scar evaluation because of its high cost. In this study, we proposed a system for scar assessment using B-mode ultrasonic technique. By utilizing the reconstruction methods to search the scar border, many characteristic parameters, including depth, area and volume, can be estimated. The proposed method is useful in assisting the clinician to evaluate the treatment effect and to plan further therapeutic strategy more objectively. In this report, the quantitative assessment system was used to evaluate the scar of a seriously burned patient. In order to verify the reliability of systematic reconstruction method, we constructed a phantom to imitate the scar tissue. The results show that it can achieve more than 90% in accuracy.

The role of ablative lasers in cutaneous scars: tissue regeneration to restore function (Conference Presentation)

NASA Astrophysics Data System (ADS)

Uebelhoer, Nathan

2017-02-01

Many laser wavelengths with various power and pulse characteristics have been used in an attempt to improve cutaneous scars. No single configuration has produced such dramatic changes in quality of life as the high energy, low density, sub-millisecond pulsed ablative infrared laser. Hundreds of wounded military service members with burn and traumatic scars that resulted in disabling restriction in range of motion have been treated since 2008. By fractionating the pulse to produce a uniform thermal injury less than 400um wide and to a depth of 3mm into the scar, we have observed dramatic reductions in scar-induced pain, pruritus, and most significantly, improvements in range of motion. The clinical and histologic changes seen in restrictive scars following treatment correlates with a regeneration of tissue that appears and functions more like normal tissue rather than scar. This lecture will describe our experience in the military and the latest research to support our observations.

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death.

PubMed

Hakeem, Abdul; Bhatti, Sabha; Dillie, Kathryn Sullivan; Cook, Jeffrey R; Samad, Zainab; Roth-Cline, Michelle D; Chang, Su Min

2008-12-09

Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001). MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.

[Scars, physiology, classification and assessment].

PubMed

Roques, Claude

2013-01-01

A skin scar is the sign of tissue repair following damage to the skin. Once formed, it follows a process of maturation which, after several months, results in a mature scar. This can be pathological with functional and/or aesthetic consequences. It is important to assess the scar as it matures in order to adapt the treatment to its evolution.

Feasibility of high-resolution quantitative perfusion analysis in patients with heart failure.

PubMed

Sammut, Eva; Zarinabad, Niloufar; Wesolowski, Roman; Morton, Geraint; Chen, Zhong; Sohal, Manav; Carr-White, Gerry; Razavi, Reza; Chiribiri, Amedeo

2015-02-12

Cardiac magnetic resonance (CMR) is playing an expanding role in the assessment of patients with heart failure (HF). The assessment of myocardial perfusion status in HF can be challenging due to left ventricular (LV) remodelling and wall thinning, coexistent scar and respiratory artefacts. The aim of this study was to assess the feasibility of quantitative CMR myocardial perfusion analysis in patients with HF. A group of 58 patients with heart failure (HF; left ventricular ejection fraction, LVEF ≤ 50%) and 33 patients with normal LVEF (LVEF >50%), referred for suspected coronary artery disease, were studied. All subjects underwent quantitative first-pass stress perfusion imaging using adenosine according to standard acquisition protocols. The feasibility of quantitative perfusion analysis was then assessed using high-resolution, 3 T kt perfusion and voxel-wise Fermi deconvolution. 30/58 (52%) subjects in the HF group had underlying ischaemic aetiology. Perfusion abnormalities were seen amongst patients with ischaemic HF and patients with normal LV function. No regional perfusion defect was observed in the non-ischaemic HF group. Good agreement was found between visual and quantitative analysis across all groups. Absolute stress perfusion rate, myocardial perfusion reserve (MPR) and endocardial-epicardial MPR ratio identified areas with abnormal perfusion in the ischaemic HF group (p = 0.02; p = 0.04; p = 0.02, respectively). In the Normal LV group, MPR and endocardial-epicardial MPR ratio were able to distinguish between normal and abnormal segments (p = 0.04; p = 0.02 respectively). No significant differences of absolute stress perfusion rate or MPR were observed comparing visually normal segments amongst groups. Our results demonstrate the feasibility of high-resolution voxel-wise perfusion assessment in patients with HF.

Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide

PubMed Central

Vandergriff, Adam; Huang, Ke; Shen, Deliang; Hu, Shiqi; Hensley, Michael Taylor; Caranasos, Thomas G.; Qian, Li; Cheng, Ke

2018-01-01

Rationale: Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies. Recent studies have used intramyocardial injection in order to concentrate exosomes in the infarct. Though effective in a research setting, this method is not clinically appealing due to its invasive nature. We propose the use of a targeting peptide, cardiac homing peptide (CHP), to target intravenously-infused exosomes to the infarcted heart. Methods: Exosomes were conjugated with CHP through a DOPE-NHS linker. Ex vivo targeting was analyzed by incubating organ sections with the CHP exosomes and analyzing with fluorescence microscopy. In vitro assays were performed on neonatal rat cardiomyocytes and H9C2 cells. For the animal study, we utilized an ischemia/reperfusion rat model. Animals were treated with either saline, scramble peptide exosomes, or CHP exosomes 24 h after surgery. Echocardiography was performed 4 h after surgery and 21 d after surgery. At 21 d, animals were sacrificed, and organs were collected for analysis. Results: By conjugating the exosomes with CHP, we demonstrate increased retention of the exosomes within heart sections ex vivo and in vitro with neonatal rat cardiomyocytes. In vitro studies showed improved viability, reduced apoptosis and increased exosome uptake when using CHP-XOs. Using an animal model of ischemia/reperfusion injury, we measured the heart function, infarct size, cellular proliferation, and angiogenesis, with improved outcomes with the CHP exosomes. Conclusions: Our results demonstrate a novel method for increasing delivery of for treatment of myocardial infarction. By targeting exosomes to the infarcted heart, there was a significant improvement in outcomes with reduced fibrosis and scar size, and increased cellular proliferation and angiogenesis. PMID:29556361

Treatment with the CC chemokine-binding protein Evasin-4 improves post-infarction myocardial injury and survival in mice.

PubMed

Braunersreuther, Vincent; Montecucco, Fabrizio; Pelli, Graziano; Galan, Katia; Proudfoot, Amanda E; Belin, Alexandre; Vuilleumier, Nicolas; Burger, Fabienne; Lenglet, Sébastien; Caffa, Irene; Soncini, Debora; Nencioni, Alessio; Vallée, Jean-Paul; Mach, François

2013-10-01

Chemokines trigger leukocyte trafficking and are implicated in cardiovascular disease pathophysiology. Chemokine-binding proteins, called "Evasins" have been shown to inhibit both CC and CXC chemokine-mediated bioactivities. Here, we investigated whether treatment with Evasin-3 (CXC chemokine inhibitor) and Evasin-4 (CC chemokine inhibitor) could influence post-infarction myocardial injury and remodelling. C57Bl/6 mice were submitted in vivo to left coronary artery permanent ligature and followed up for different times (up to 21 days). After coronary occlusion, three intraperitoneal injections of 10 μg Evasin-3, 1 μg Evasin-4 or equal volume of vehicle (PBS) were performed at 5 minutes, 24 hours (h) and 48 h after ischaemia onset. Both anti-chemokine treatments were associated with the beneficial reduction in infarct size as compared to controls. This effect was accompanied by a decrease in post-infarction myocardial leukocyte infiltration, reactive oxygen species release, and circulating levels of CXCL1 and CCL2. Treatment with Evasin-4 induced a more potent effect, abrogating the inflammation already at one day after ischaemia onset. At days 1 and 21 after ischaemia onset, both anti-chemokine treatments failed to significantly improve cardiac function, remodelling and scar formation. At 21-day follow-up, mouse survival was exclusively improved by Evasin-4 treatment when compared to control vehicle. In conclusion, we showed that the selective inhibition of CC chemokines (i.e. CCL5) with Evasin-4 reduced cardiac injury/inflammation and improved survival. Despite the inhibition of CXC chemokine bioactivities, Evasin-3 did not affect mouse survival. Therefore, early inhibition of CC chemokines might represent a promising therapeutic approach to reduce the development of post-infarction heart failure in mice.

Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation

PubMed Central

Shen, Chong; Jiang, Lifang; Shao, Huawei; You, Chuangang; Zhang, Guoliang; Ding, Sitong; Bian, Tingwei; Han, Chunmao; Meng, Qin

2016-01-01

Pathological myofibroblasts are often involved in skin scarring via generating contractile force and over-expressing collagen fibers, but no compound has been found to inhibit the myofibroblasts without showing severe toxicity to surrounding physiological cells. Here we report that di-rhamnolipid, a biosurfactant secreted by Pseudomonas aeruginosa, showed potent effects on scar therapy via a unique mechanism of targeted killing the myofibroblasts. In cell culture, the fibroblasts-derived myofibroblasts were more sensitive to di-rhamnolipid toxicity than fibroblasts at a concentration-dependent manner, and could be completely inhibited of their specific functions including α-SMA expression and collagen secretion/contraction. The anti-fibrotic function of di-rhamnolipid was further verified in rabbit ear hypertrophic scar models by presenting the significant reduction of scar elevation index, type I collagen fibers and α-SMA expression. In this regard, di-rhamnolipid treatment could be suggested as a therapy against skin scarring. PMID:27901027

Oxygen-dependent quenching of phosphorescence used to characterize improved myocardial oxygenation resulting from vasculogenic cytokine therapy

PubMed Central

Hiesinger, William; Vinogradov, Sergei A.; Atluri, Pavan; Fitzpatrick, J. Raymond; Frederick, John R.; Levit, Rebecca D.; McCormick, Ryan C.; Muenzer, Jeffrey R.; Yang, Elaine C.; Marotta, Nicole A.; MacArthur, John W.; Wilson, David F.

2011-01-01

This study evaluates a therapy for infarct modulation and acute myocardial rescue and utilizes a novel technique to measure local myocardial oxygenation in vivo. Bone marrow-derived endothelial progenitor cells (EPCs) were targeted to the heart with peri-infarct intramyocardial injection of the potent EPC chemokine stromal cell-derived factor 1α (SDF). Myocardial oxygen pressure was assessed using a noninvasive, real-time optical technique for measuring oxygen pressures within microvasculature based on the oxygen-dependent quenching of the phosphorescence of Oxyphor G3. Myocardial infarction was induced in male Wistar rats (n = 15) through left anterior descending coronary artery ligation. At the time of infarction, animals were randomized into two groups: saline control (n = 8) and treatment with SDF (n = 7). After 48 h, the animals underwent repeat thoracotomy and 20 μl of the phosphor Oxyphor G3 was injected into three areas (peri-infarct myocardium, myocardial scar, and remote left hindlimb muscle). Measurements of the oxygen distribution within the tissue were then made in vivo by applying the end of a light guide to the beating heart. Compared with controls, animals in the SDF group exhibited a significantly decreased percentage of hypoxic (defined as oxygen pressure ≤ 15.0 Torr) peri-infarct myocardium (9.7 ± 6.7% vs. 21.8 ± 11.9%, P = 0.017). The peak oxygen pressures in the peri-infarct region of the animals in the SDF group were significantly higher than the saline controls (39.5 ± 36.7 vs. 9.2 ± 8.6 Torr, P = 0.02). This strategy for targeting EPCs to vulnerable peri-infarct myocardium via the potent chemokine SDF-1α significantly decreased the degree of hypoxia in peri-infarct myocardium as measured in vivo by phosphorescence quenching. This effect could potentially mitigate the vicious cycle of myocyte death, myocardial fibrosis, progressive ventricular dilatation, and eventual heart failure seen after acute myocardial infarction. PMID:21292844

Phaeochromocytoma found on cardiovascular magnetic resonance in a patient presenting with acute myocarditis: an unusual association.

PubMed

Khattak, Sophia; Sim, Iain; Dancy, Luke; Whitelaw, Benjamin; Sado, Dan

2018-06-08

Myocarditis is inflammation of the cardiac muscle. The symptoms, signs and basic investigation findings can mimic that of myocardial infarction. The most common cause is infection (most commonly viral). Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive diagnostic test for potential acute myocarditis as it allows assessment of myocardial oedema and scar. A man aged 25 years was admitted with chest pain, dizziness, headache, palpitations and sweating. His troponin was mildly positive. A CMR was performed which showed mild myocarditis and a right suprarenal mass which was confirmed to be a phaeochromocytoma based on biochemistry and a dedicated imaging workup. Phaeochromocytoma can lead to cardiac involvement in the form of left ventricular dysfunction, or catecholamine-induced myocarditis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Computer-based assessment of left ventricular regional ejection fraction in patients after myocardial infarction

NASA Astrophysics Data System (ADS)

Teo, S.-K.; Su, Y.; Tan, R. S.; Zhong, L.

2014-03-01

After myocardial infarction (MI), the left ventricle (LV) undergoes progressive remodeling which adversely affects heart function and may lead to development of heart failure. There is an escalating need to accurately depict the LV remodeling process for disease surveillance and monitoring of therapeutic efficacy. Current practice of using ejection fraction to quantitate LV function is less than ideal as it obscures regional variation and anomaly. Therefore, we sought to (i) develop a quantitative method to assess LV regional ejection fraction (REF) using a 16-segment method, and (ii) evaluate the effectiveness of REF in discriminating 10 patients 1-3 months after MI and 9 normal control (sex- and agematched) based on cardiac magnetic resonance (CMR) imaging. Late gadolinium enhancement (LGE) CMR scans were also acquired for the MI patients to assess scar extent. We observed that the REF at the basal, mid-cavity and apical regions for the patient group is significantly lower as compared to the control group (P < 0.001 using a 2-tail student t-test). In addition, we correlated the patient REF over these regions with their corresponding LGE score in terms of 4 categories - High LGE, Low LGE, Border and Remote. We observed that the median REF decreases with increasing severity of infarction. The results suggest that REF could potentially be used as a discriminator for MI and employed to measure myocardium homogeneity with respect to degree of infarction. The computational performance per data sample took approximately 25 sec, which demonstrates its clinical potential as a real-time cardiac assessment tool.

Tc-99m Ethylenedicysteine and Tc-99m Dimercaptosuccinic Acid Scintigraphy-Comparison of the Two for Detection of Scarring and Differential Cortical Function.

PubMed

Dharmalingam, Anitha; Pawar, Shwetal U; Parelkar, Sandesh V; Shetye, Suruchi S; Ghorpade, Mangala K; Tilve, Gundu H

2017-01-01

The differential cortical function obtained by Tc-99m EC is comparable to that of Tc-99m DMSA. However, identification of scars on Tc-99m EC images needs to be studied. The aim of the study is to evaluate role of Tc-99m EC for detection of scarring and differential cortical function by comparing with Tc-99m DMSA. Prospective observational study of recurrent UTI; minimum 6 weeks after acute episode; when urine examination is negative for pus cells. Forty-seven children with normal positioned kidneys underwent Tc-99m EC and DMSA scintigraphy. The DRF and cortical phase images of both studies in the same image matrix size were evaluated by two independent observers for scarring; Tc-99m DMSA was considered as the gold standard. MS Excel 2007 and GraphPad Instat V3.1 and ROC analysis. There was no significant difference in the detection of scarring using two studies with Cohen's kappa coefficient (κ) 0.932. The sensitivity and specificity of Tc-99m EC for detection of scarring was 98.75% and 99.15%, respectively. There was good agreement between the differential cortical function calculated using two studies. The summed Tc-99m EC images with an acceptable high image contrast allow detection of cortical scarring in patients with normal kidney positions. It is an excellent single-modality comprehensive investigational agent for renal parenchymal defects, function, and excretion evaluation with the added advantages of lower cost, convenience, and low radiation exposure to the child.

Cardiovascular magnetic resonance of myocardial edema using a short inversion time inversion recovery (STIR) black-blood technique: Diagnostic accuracy of visual and semi-quantitative assessment

PubMed Central

2012-01-01

Background The short inversion time inversion recovery (STIR) black-blood technique has been used to visualize myocardial edema, and thus to differentiate acute from chronic myocardial lesions. However, some cardiovascular magnetic resonance (CMR) groups have reported variable image quality, and hence the diagnostic value of STIR in routine clinical practice has been put into question. The aim of our study was to analyze image quality and diagnostic performance of STIR using a set of pulse sequence parameters dedicated to edema detection, and to discuss possible factors that influence image quality. We hypothesized that STIR imaging is an accurate and robust way of detecting myocardial edema in non-selected patients with acute myocardial infarction. Methods Forty-six consecutive patients with acute myocardial infarction underwent CMR (day 4.5, +/- 1.6) including STIR for the assessment of myocardial edema and late gadolinium enhancement (LGE) for quantification of myocardial necrosis. Thirty of these patients underwent a follow-up CMR at approximately six months (195 +/- 39 days). Both STIR and LGE images were evaluated separately on a segmental basis for image quality as well as for presence and extent of myocardial hyper-intensity, with both visual and semi-quantitative (threshold-based) analysis. LGE was used as a reference standard for localization and extent of myocardial necrosis (acute) or scar (chronic). Results Image quality of STIR images was rated as diagnostic in 99.5% of cases. At the acute stage, the sensitivity and specificity of STIR to detect infarcted segments on visual assessment was 95% and 78% respectively, and on semi-quantitative assessment was 99% and 83%, respectively. STIR differentiated acutely from chronically infarcted segments with a sensitivity of 95% by both methods and with a specificity of 99% by visual assessment and 97% by semi-quantitative assessment. The extent of hyper-intense areas on acute STIR images was 85% larger than those on LGE images, with a larger myocardial salvage index in reperfused than in non-reperfused infarcts (p = 0.035). Conclusions STIR with appropriate pulse sequence settings is accurate in detecting acute myocardial infarction (MI) and distinguishing acute from chronic MI with both visual and semi-quantitative analysis. Due to its unique technical characteristics, STIR should be regarded as an edema-weighted rather than a purely T2-weighted technique. PMID:22455461

Scars of the Wigner Function.

PubMed

Toscano; de Aguiar MA; Ozorio De Almeida AM

2001-01-01

We propose a picture of Wigner function scars as a sequence of concentric rings along a two-dimensional surface inside a periodic orbit. This is verified for a two-dimensional plane that contains a classical hyperbolic orbit of a Hamiltonian system with 2 degrees of freedom. The stationary wave functions are the familiar mixture of scarred and random waves, but the spectral average of the Wigner functions in part of the plane is nearly that of a harmonic oscillator and individual states are also remarkably regular. These results are interpreted in terms of the semiclassical picture of chords and centers.

Fully automatic left ventricular myocardial strain estimation in 2D short-axis tagged magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Morais, Pedro; Queirós, Sandro; Heyde, Brecht; Engvall, Jan; 'hooge, Jan D.; Vilaça, João L.

2017-09-01

Cardiovascular diseases are among the leading causes of death and frequently result in local myocardial dysfunction. Among the numerous imaging modalities available to detect these dysfunctional regions, cardiac deformation imaging through tagged magnetic resonance imaging (t-MRI) has been an attractive approach. Nevertheless, fully automatic analysis of these data sets is still challenging. In this work, we present a fully automatic framework to estimate left ventricular myocardial deformation from t-MRI. This strategy performs automatic myocardial segmentation based on B-spline explicit active surfaces, which are initialized using an annular model. A non-rigid image-registration technique is then used to assess myocardial deformation. Three experiments were set up to validate the proposed framework using a clinical database of 75 patients. First, automatic segmentation accuracy was evaluated by comparing against manual delineations at one specific cardiac phase. The proposed solution showed an average perpendicular distance error of 2.35  ±  1.21 mm and 2.27  ±  1.02 mm for the endo- and epicardium, respectively. Second, starting from either manual or automatic segmentation, myocardial tracking was performed and the resulting strain curves were compared. It is shown that the automatic segmentation adds negligible differences during the strain-estimation stage, corroborating its accuracy. Finally, segmental strain was compared with scar tissue extent determined by delay-enhanced MRI. The results proved that both strain components were able to distinguish between normal and infarct regions. Overall, the proposed framework was shown to be accurate, robust, and attractive for clinical practice, as it overcomes several limitations of a manual analysis.

Post-burn scars and scar contractures

PubMed Central

Goel, Arun; Shrivastava, Prabhat

2010-01-01

The mortality and morbidity from burns have diminished tremendously over the last six to seven decades. However, these do not truly reflect whether the victim could go back to society as a useful person or not and lead a normal life because of the inevitable post-burn scars, contractures and other deformities which collectively have aesthetic and functional considerations. This article gives an overview of the post-burn scars and scar contractures, especially their prevention, minimisation and principles of management. PMID:21321660

Presence of reduced regional left ventricular function even in the absence of left ventricular wall scar tissue in the long term after repair of an anomalous left coronary artery from the pulmonary artery.

PubMed

Nordmeyer, Sarah; Schmitt, Boris; Nasseri, Boris; Alexi-Meskishvili, Vladimir; Kuehne, Titus; Berger, Felix; Nordmeyer, Johannes

2018-02-01

We sought to assess left ventricular regional function in patients with and without left ventricular wall scar tissue in the long term after repair of an anomalous origin of the left coronary artery from the pulmonary artery. A total of 20 patients aged 12.8±7.4 years were assessed 10 (0.5-17) years after the repair of an anomalous origin of the left coronary artery from the pulmonary artery; of them, 10 (50%) patients showed left ventricular wall scar tissue on current cardiac MRI. Left ventricular regional function was assessed by two-dimensional speckle-tracking echocardiography in 10 patients with scar tissue and 10 patients without scar tissue and in 10 age-matched controls. In patients with scar tissue, MRI-derived left ventricular ejection fraction was significantly reduced compared with that in patients without scar tissue (51 versus 61%, p<0.05), and echocardiography-derived longitudinal strain was significantly reduced in five of six left ventricular areas compared with that in healthy controls (average relative reduction, 46%; p<0.05). In patients without scar tissue, longitudinal strain was significantly reduced in two of six left ventricular areas (average relative reduction, 23%; p<0.05) and circumferential strain was reduced in one of six left ventricular areas (relative reduction, 56%; p<0.05) compared with that in healthy controls. Regional left ventricular function is reduced even in patients without left ventricular wall scar tissue late after successful repair of an anomalous origin of the left coronary artery from the pulmonary artery. This highlights the need for meticulous lifelong follow-up in all patients with a repaired anomalous origin of the left coronary artery from the pulmonary artery.

Functioning before and after a major depressive episode: pre-existing vulnerability or scar? A prospective three-wave population-based study.

PubMed

Bos, E H; Ten Have, M; van Dorsselaer, S; Jeronimus, B F; de Graaf, R; de Jonge, P

2018-01-14

The vulnerability hypothesis suggests that impairments after remission of depressive episodes reflect a pre-existing vulnerability, while the scar hypothesis proposes that depression leaves residual impairments that confer risk of subsequent episodes. We prospectively examined vulnerability and scar effects in mental and physical functioning in a representative Dutch population sample. Three waves were used from the Netherlands Mental Health Survey and Incidence Study-2, a population-based study with a 6-years follow-up. Mental and physical functioning were assessed with the Medical Outcomes Study Short Form (SF-36). Major depressive disorder (MDD) was assessed with the Composite International Diagnostic Interview 3.0. Vulnerability effects were examined by comparing healthy controls (n = 2826) with individuals who developed a first-onset depressive episode during first follow-up but did not have a lifetime diagnosis of MDD at baseline (n = 181). Scarring effects were examined by comparing pre- and post-morbid functioning in individuals who developed a depressive episode after baseline that was remitted at the third wave (n = 108). Both mental (B = -5.4, s.e. = 0.9, p < 0.001) and physical functioning (B = -8.2, s.e. = 1.1, p < 0.001) at baseline were lower in individuals who developed a first depressive episode after baseline compared with healthy controls. This effect was most pronounced in people who developed a severe episode. No firm evidence of scarring in mental or physical functioning was found. In unadjusted analyses, physical functioning was still lowered post-morbidly (B = -5.1, s.e. = 2.1, p = 0.014), but this effect disappeared in adjusted analyses. Functional impairments after remission of depression seem to reflect a pre-existing vulnerability rather than a scar.

Handheld SFDI/polarimetric imaging device for objective evaluation of hypertrophic scars (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ramella-Roman, Jessica C.; Montejo, Karla; Sevilla, Nicole; Stoff, Susan; Gonzalez, Mariacarla; Chue-Sang, Joseph

2017-02-01

Scars can be debilitating and cause serious functional limitations, significantly reduced physical function and loss of ability to perform normal daily activities. Scar formation is not fully understood and the treatment options have been hampered by the lack of an objective diagnostic tool to assess scars. Presently, assessment of hypertrophic scars has been based on subjective clinician rankings using a four-parameter scale called the Vancouver Scar Scale (VSS) or the Patient Observer Scar Assessment Scale (POSAS) but no objective, standardized tool for quantifying scar severity is available, despite known inadequacies of the subjective scales. We have developed a hand-held multi modal system consisting of a combined Spatial Frequency Domain Imager (SFDI) used for the assessment of tissue molecular components and a polarimeter for structural measurements. The SFDI capability is provided by an Arduino board controlled spectrally and polarimetric diverse Light Emitting Diodes (LED) ring illuminator. For SFDI imagery, the LEDs are combined with sinusoidal patterns. A single pattern snapshot SFDI approach is used to observe and quantify the biological components in the scar tissue including: oxygenated and de oxygenated hemoglobin, water, and melanin. The SFDI system is integrated with a reduced Mueller Matrix polarimetric system, whose illumination is also included in the LED's ring, and providing for the assessment of collagen orientation through Mueller Matrix decomposition. The design of the system and experimental work on phantoms will be presented.

Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

PubMed

van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

2016-01-01

Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.

The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis

PubMed Central

Prabhu, Sumanth D.; Frangogiannis, Nikolaos G.

2016-01-01

In adult mammals, massive sudden loss of cardiomyocytes following infarction overwhelms the limited regenerative capacity of the myocardium, resulting in formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimulation of toll-like receptor signaling and complement activation induces expression of pro-inflammatory cytokines (such as interleukin-1 and tumor necrosis factor-α) and chemokines (such as monocyte chemoattractant protein-1/CCL2). Inflammatory signals promote adhesive interactions between leukocytes and endothelial cells, leading to extravasation of neutrophils and monocytes. As infiltrating leukocytes clear the infarct from dead cells, mediators repressing inflammation are released, and anti-inflammatory mononuclear cell subsets predominate. Suppression of the inflammatory response is associated with activation of reparative cells. Fibroblasts proliferate, undergo myofibroblast transdifferentiation, and deposit large amounts of extracellular matrix proteins maintaining the structural integrity of the infarcted ventricle. The renin-angiotensin-aldosterone system and members of the transforming growth factor-β family play an important role in activation of infarct myofibroblasts. Maturation of the scar follows, as a network of cross-linked collagenous matrix is formed and granulation tissue cells become apoptotic. This review discusses the cellular effectors and molecular signals regulating the inflammatory and reparative response following myocardial infarction. Dysregulation of immune pathways, impaired suppression of post-infarction inflammation, perturbed spatial containment of the inflammatory response, and overactive fibrosis may cause adverse remodeling in patients with infarction contributing to the pathogenesis of heart failure. Therapeutic modulation of the inflammatory and reparative response may hold promise for prevention of post-infarction heart failure. PMID:27340270

Sustained IGF-1 Secretion by Adipose-Derived Stem Cells Improves Infarcted Heart Function.

PubMed

Bagno, Luiza L; Carvalho, Deivid; Mesquita, Fernanda; Louzada, Ruy A; Andrade, Bruno; Kasai-Brunswick, Taís H; Lago, Vivian M; Suhet, Grazielle; Cipitelli, Debora; Werneck-de-Castro, João Pedro; Campos-de-Carvalho, Antonio C

2016-01-01

The mechanism by which stem cell-based therapy improves heart function is still unknown, but paracrine mechanisms seem to be involved. Adipose-derived stem cells (ADSCs) secrete several factors, including insulin-like growth factor-1 (IGF-1), which may contribute to myocardial regeneration. Our aim was to investigate whether the overexpression of IGF-1 in ADSCs (IGF-1-ADSCs) improves treatment of chronically infarcted rat hearts. ADSCs were transduced with a lentiviral vector to induce IGF-1 overexpression. IGF-1-ADSCs transcribe100- to 200-fold more IGF-1 mRNA levels compared to nontransduced ADSCs. IGF-1 transduction did not alter ADSC immunophenotypic characteristics even under hypoxic conditions. However, IGF-1-ADSCs proliferate at higher rates and release greater amounts of growth factors such as IGF-1, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) under normoxic and hypoxic conditions. Importantly, IGF-1 secreted by IGF-1-ADSCs is functional given that Akt-1 phosphorylation was remarkably induced in neonatal cardiomyocytes cocultured with IGF-1-ADSCs, and this increase was prevented with phosphatidylinositol 3-kinase (PI3K) inhibitor treatment. Next, we tested IGF-1-ADSCs in a rat myocardial infarction (MI) model. MI was performed by coronary ligation, and 4 weeks after MI, animals received intramyocardial injections of either ADSCs (n = 7), IGF-1-ADSCs (n = 7), or vehicle (n = 7) into the infarcted border zone. Left ventricular function was evaluated by echocardiography before and after 6 weeks of treatment, and left ventricular hemodynamics were assessed 7 weeks after cell injection. Notably, IGF-1-ADSCs improved left ventricular ejection fraction and cardiac contractility index, but did not reduce scar size when compared to the ADSC-treated group. In summary, transplantation of ADSCs transduced with IGF-1 is a superior therapeutic approach to treat MI compared to nontransduced ADSCs, suggesting that gene and cell therapy may bring additional benefits to the treatment of MI.

Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism.

PubMed

Sun, Dan; Yang, Fei

2017-04-29

To investigate whether metformin can improve the cardiac function through improving the mitochondrial function in model of heart failure after myocardial infarction. Male C57/BL6 mice aged about 8 weeks were selected and the anterior descending branch was ligatured to establish the heart failure model after myocardial infarction. The cardiac function was evaluated via ultrasound after 3 days to determine the modeling was successful, and the mice were randomly divided into two groups. Saline group (Saline) received the intragastric administration of normal saline for 4 weeks, and metformin group (Met) received the intragastric administration of metformin for 4 weeks. At the same time, Shame group (Sham) was set up. Changes in cardiac function in mice were detected at 4 weeks after operation. Hearts were taken from mice after 4 weeks, and cell apoptosis in myocardial tissue was detected using TUNEL method; fresh mitochondria were taken and changes in oxygen consumption rate (OCR) and respiratory control rate (RCR) of mitochondria in each group were detected using bio-energy metabolism tester, and change in mitochondrial membrane potential (MMP) of myocardial tissue was detected via JC-1 staining; the expressions and changes in Bcl-2, Bax, Sirt3, PGC-1α and acetylated PGC-1α in myocardial tissue were detected by Western blot. RT-PCR was used to detect mRNA levels in Sirt3 in myocardial tissues. Metformin improved the systolic function of heart failure model rats after myocardial infarction and reduced the apoptosis of myocardial cells after myocardial infarction. Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1α in myocardial tissue of heart failure after myocardial infarction. Metformin decreases the acetylation level of PGC-1α through up-regulating Sirt3, mitigates the damage to mitochondrial membrane potential of model of heart failure after myocardial infarction and improves the respiratory function of mitochondria, thus improving the cardiac function of mice. Copyright © 2017. Published by Elsevier Inc.

Update on hypertrophic scar treatment

PubMed Central

Rabello, Felipe Bettini; Souza, Cleyton Dias; Júnior, Jayme Adriano Farina

2014-01-01

Scar formation is a consequence of the wound healing process that occurs when body tissues are damaged by a physical injury. Hypertrophic scars and keloids are pathological scars resulting from abnormal responses to trauma and can be itchy and painful, causing serious functional and cosmetic disability. The current review will focus on the definition of hypertrophic scars, distinguishing them from keloids and on the various methods for treating hypertrophic scarring that have been described in the literature, including treatments with clearly proven efficiency and therapies with doubtful benefits. Numerous methods have been described for the treatment of abnormal scars, but to date, the optimal treatment method has not been established. This review will explore the differences between different types of nonsurgical management of hypertrophic scars, focusing on the indications, uses, mechanisms of action, associations and efficacies of the following therapies: silicone, pressure garments, onion extract, intralesional corticoid injections and bleomycin. PMID:25141117

Recent Understandings of Biology, Prophylaxis and Treatment Strategies for Hypertrophic Scars and Keloids

PubMed Central

Jang, Yong Ju

2018-01-01

Hypertrophic scars and keloids are fibroproliferative disorders that may arise after any deep cutaneous injury caused by trauma, burns, surgery, etc. Hypertrophic scars and keloids are cosmetically problematic, and in combination with functional problems such as contractures and subjective symptoms including pruritus, these significantly affect patients’ quality of life. There have been many studies on hypertrophic scars and keloids; but the mechanisms underlying scar formation have not yet been well established, and prophylactic and treatment strategies remain unsatisfactory. In this review, the authors introduce and summarize classical concepts surrounding wound healing and review recent understandings of the biology, prevention and treatment strategies for hypertrophic scars and keloids. PMID:29498630

Elastin Is Differentially Regulated by Pressure Therapy in a Porcine Model of Hypertrophic Scar.

PubMed

Carney, Bonnie C; Liu, Zekun; Alkhalil, Abdulnaser; Travis, Taryn E; Ramella-Roman, Jessica; Moffatt, Lauren T; Shupp, Jeffrey W

Beneficial effects of pressure therapy for hypertrophic scars have been reported, but the mechanisms of action are not fully understood. This study evaluated elastin and its contribution to scar pliability. The relationship between changes in Vancouver Scar Scale (VSS) scores of pressure-treated scars and differential regulation of elastin was assessed. Hypertrophic scars were created and assessed weekly using VSS and biopsy procurement. Pressure treatment began on day 70 postinjury. Treated scars were compared with untreated shams. Treatment lasted 2 weeks, through day 84, and scars were assessed weekly through day 126. Transcript and protein levels of elastin were quantified. Pressure treatment resulted in lower VSS scores compared with sham-treated scars. Pliability (VSSP) was a key contributor to this difference. At day 70 pretreatment, VSSP = 2. Without treatment, sham-treated scars became less pliable, while pressure-treated scars became more pliable. The percentage of elastin in scars at day 70 was higher than in uninjured skin. Following treatment, the percentage of elastin increased and continued to increase through day 126. Untreated sham scars did not show a similar increase. Quantification of Verhoeff-Van Gieson staining corroborated the findings and immunofluorescence revealed the alignment of elastin fibers. Pressure treatment results in increased protein level expression of elastin compared with sham-untreated scars. These findings further characterize the extracellular matrix's response to the application of pressure as a scar treatment, which will contribute to the refinement of rehabilitation practices and ultimately improvements in functional and psychosocial outcomes for patients.

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography: a comparison with contrast-enhanced magnetic resonance imaging.

PubMed

Nelson, Charles; McCrohon, Jane; Khafagi, Frederick; Rose, Stephen; Leano, Rodel; Marwick, Thomas H

2004-04-07

We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, <25%, 26% to 50%, 51% to 75%, and >75% of the wall thickness replaced by scar. As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (<25% TES), >50% were viable by SPECT. Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar.

Utility of late gadolinium enhancement in pediatric cardiac MRI.

PubMed

Etesami, Maryam; Gilkeson, Robert C; Rajiah, Prabhakar

2016-07-01

Late gadolinium enhancement (LGE) cardiac magnetic resonance (MR) imaging sequence is increasingly used in the evaluation of pediatric cardiovascular disorders, and although LGE might be a normal feature at the sites of previous surgeries, it is pathologically seen as a result of extracellular space expansion, either from acute cell damage or chronic scarring or fibrosis. LGE is broadly divided into ischemic and non-ischemic patterns. LGE caused by myocardial infarction occurs in a vascular distribution and always involves the subendocardial portion, progressively involving the outer regions in a waveform pattern. Non-ischemic cardiomyopathies can have a mid-myocardial (either linear or patchy), subepicardial or diffuse subendocardial distribution. Idiopathic dilated cardiomyopathy can have a linear mid-myocardial pattern, while hypertrophic cardiomyopathy can have fine, patchy enhancement in hypertrophied and non-hypertrophied segments as well as right ventricular insertion points. Myocarditis and sarcoidosis have a mid-myocardial or subepicardial pattern of LGE. Fabry disease typically affects the basal inferolateral segment while Danon disease typically spares the septum. Pericarditis is characterized by diffuse or focal pericardial thickening and enhancement. Thrombus, the most common non-neoplastic cardiac mass, is characterized by absence of enhancement in all sequences, while neoplastic masses show at least some contrast enhancement, depending on the pathology. Regardless of the etiology, presence of LGE is associated with a poor prognosis. In this review, we describe the technical modifications required for performing LGE cardiac MR sequence in children, review and illustrate the patterns of LGE in children, and discuss their clinical significance.

Prevention and therapy of postburn scars.

PubMed

Bláha, J; Pondĕlicek, I

1997-01-01

The cosmetic and functional result in postburn scar deformities is influenced by following factors: 1. The type of patient's central nervous system and his response to burn injury. 2. Depth and site of burn areas. 3. Early excision and grafting. 4. Infection complications, their severity and location. 5. Fixation of dressings should be done using elastic materials and applied for so long until stabilisation of scars is completed. Elastic materials should be combined with rigid pressure and pressure massage. 6. Congenital predisposition of the patient to hypertrophic scarring.

Shine on: Review of Laser- and Light-Based Therapies for the Treatment of Burn Scars

PubMed Central

Hultman, C. Scott; Edkins, Renee E.; Lee, Clara N.; Calvert, Catherine T.; Cairns, Bruce A.

2012-01-01

Restoration of form and function after burn injury remains challenging, but emerging laser and pulsed light technologies now offer hope for patients with hypertrophic scars, which may be associated with persistent hyperemia, chronic folliculitis, intense pruritis, and neuropathic pain. In addition to impairing body image, these scars may limit functional recovery, compromise activities of daily living, and prevent return to work. Three different platforms are now poised to alter our reconstructive algorithm: (1) vascular-specific pulsed dye laser (PDL) to reduce hyperemia, (2) ablative fractional CO2 laser to improve texture and pliability of the burn scar, and (3) intense pulsed light (IPL) to correct burn scar dyschromia and alleviate chronic folliculitis. In this paper, we will provide an overview of our work in this area, which includes a systematic review, a retrospective analysis of our preliminary experience, and interim data from our on-going, prospective, before-after cohort trial. We will demonstrate that laser- and light-based therapies can be combined with each other safely to yield superior results, often at lower cost, by reducing the need for reconstructive surgery. Modulating the burn scar, through minimally invasive modalities, may replace conventional methods of burn scar excision and yield outcomes not previously possible or conceivable. PMID:22778719

The effects of advanced glycation end products (AGEs) on dermal wound healing and scar formation: a systematic review

PubMed Central

Van Putte, Lennert; De Schrijver, Sofie; Moortgat, Peter

2016-01-01

Introduction: With ageing, the skin gradually loses its youthful appearance and functions like wound healing and scar formation. The pathophysiological theory of Advanced Glycation End products (AGEs) has gained traction during the last decade. This review aims to document the influence of AGEs on the mechanical and physiologic properties of the skin, how they affect dermal wound healing and scar formation in high-AGE populations like elderly patients and diabetics, and potential therapeutic strategies. Methods: This systematic literature study involved a structured search in Pubmed and Web of Science with qualitative analysis of 14 articles after a three-staged selection process with the use of in- and exclusion criteria. Results: Overall, AGEs cause shortened, thinned, and disorganized collagen fibrils, consequently reducing elasticity and skin/scar thickness with increased contraction and delayed wound closure. Documented therapeutic strategies include dietary AGE restriction, sRAGE decoy receptors, aminoguanidine, RAGE-blocking antibodies, targeted therapy, thymosin β4, anti-oxidant agents and gold nanoparticles, ethyl pyruvate, Gal-3 manipulation and metformin. Discussion: With lack of evidence concerning scars, no definitive conclusions can yet be made about the role of AGEs on possible appearance or function of scar tissue. However, all results suggest that scars tend to be more rigid and contractile with persistent redness and reduced tendency towards hypertrophy as AGEs accumulate. Conclusion: Abundant evidence supports the pathologic role of AGEs in ageing and dermal wound healing and the effectiveness of possible therapeutic agents. More research is required to conclude its role in scar formation and scar therapy.

Perioperative Assessment of Myocardial Deformation

PubMed Central

Duncan, Andra E.; Alfirevic, Andrej; Sessler, Daniel I.; Popovic, Zoran B.; Thomas, James D.

2014-01-01

Evaluation of left ventricular performance improves risk assessment and guides anesthetic decisions. However, the most common echocardiographic measure of myocardial function, the left ventricular ejection fraction (LVEF), has important limitations. LVEF is limited by subjective interpretation which reduces accuracy and reproducibility, and LVEF assesses global function without characterizing regional myocardial abnormalities. An alternative objective echocardiographic measure of myocardial function is thus needed. Myocardial deformation analysis, which performs quantitative assessment of global and regional myocardial function, may be useful for perioperative care of surgical patients. Myocardial deformation analysis evaluates left ventricular mechanics by quantifying strain and strain rate. Strain describes percent change in myocardial length in the longitudinal (from base to apex) and circumferential (encircling the short-axis of the ventricle) direction and change in thickness in the radial direction. Segmental strain describes regional myocardial function. Strain is a negative number when the ventricle shortens longitudinally or circumferentially and is positive with radial thickening. Reference values for normal longitudinal strain from a recent meta-analysis using transthoracic echocardiography are (mean ± SD) −19.7 ± 0.4%, while radial and circumferential strain are 47.3 ± 1.9 and −23.3 ± 0.7%, respectively. The speed of myocardial deformation is also important and is characterized by strain rate. Longitudinal systolic strain rate in healthy subjects averages −1.10 ± 0.16 sec−1. Assessment of myocardial deformation requires consideration of both strain (change in deformation), which correlates with LVEF, and strain rate (speed of deformation), which correlates with rate of rise of left ventricular pressure (dP/dt). Myocardial deformation analysis also evaluates ventricular relaxation, twist, and untwist, providing new and noninvasive methods to assess components of myocardial systolic and diastolic function. Myocardial deformation analysis is based on either Doppler or a non-Doppler technique, called speckle-tracking echocardiography. Myocardial deformation analysis provides quantitative measures of global and regional myocardial function for use in the perioperative care of the surgical patient. For example, coronary graft occlusion after coronary artery bypass grafting is detected by an acute reduction in strain in the affected coronary artery territory. In addition, assessment of left ventricular mechanics detects underlying myocardial pathology before abnormalities become apparent on conventional echocardiography. Certainly, patients with aortic regurgitation demonstrate reduced longitudinal strain before reduction in LVEF occurs, which allows detection of subclinical left ventricular dysfunction and predicts increased risk for heart failure and impaired myocardial function after surgical repair. In this review we describe the principles, techniques, and clinical application of myocardial deformation analysis. PMID:24557101

Cardio-chemical exchange saturation transfer magnetic resonance imaging reveals molecular signatures of endogenous fibrosis and exogenous contrast media.

PubMed

Vandsburger, Moriel; Vandoorne, Katrien; Oren, Roni; Leftin, Avigdor; Mpofu, Senzeni; Delli Castelli, Daniela; Aime, Silvio; Neeman, Michal

2015-01-01

Application of emerging molecular MRI techniques, including chemical exchange saturation transfer (CEST)-MRI, to cardiac imaging is desirable; however, conventional methods are poorly suited for cardiac imaging, particularly in small animals with rapid heart rates. We developed a CEST-encoded steady state and retrospectively gated cardiac cine imaging sequence in which the presence of fibrosis or paraCEST contrast agents was directly encoded into the steady-state myocardial signal intensity (cardioCEST). Development of cardioCEST: A CEST-encoded cardiac cine MRI sequence was implemented on a 9.4T small animal scanner. CardioCEST of fibrosis was serially performed by acquisition of a series of CEST-encoded cine images at multiple offset frequencies in mice (n=7) after surgically induced myocardial infarction. Scar formation was quantified using a spectral modeling approach and confirmed with histological staining. Separately, circulatory redistribution kinetics of the paramagnetic CEST agent Eu-HPDO3A were probed in mice using cardioCEST imaging, revealing rapid myocardial redistribution, and washout within 30 minutes (n=6). Manipulation of vascular tone resulted in heightened peak CEST contrast in the heart, but did not alter redistribution kinetics (n=6). At 28 days after myocardial infarction (n=3), CEST contrast kinetics in infarct zone tissue were altered, demonstrating gradual accumulation of Eu-HPDO3A in the increased extracellular space. cardioCEST MRI enables in vivo imaging of myocardial fibrosis using endogenous contrast mechanisms, and of exogenously delivered paraCEST agents, and can enable multiplexed imaging of multiple molecular targets at high-resolution coupled with conventional cardiac MRI scans. © 2013 American Heart Association, Inc.

Effects of silicone gel on burn scars.

PubMed

Momeni, Mahnoush; Hafezi, Farhad; Rahbar, Hossein; Karimi, Hamid

2009-02-01

To study the efficacy of silicone gel applied to hypertrophic burn scars, in reducing scar interference with normal function and improving cosmesis. A randomised, double-blind, placebo-controlled trial involving 38 people with hypertrophic burn scars. Each scar was divided into two segments; silicone gel sheet was applied randomly to one of the two and placebo to the other. Participants were seen again after 1 and 4 months. Their data and wound characteristics were collected using the Vancouver scar scale. The median age of participants was 22 years (1.5-60 years) and 16 were male; 4 did not attend follow-up and were excluded from the study. There were no significant differences in baseline characteristics. Although after 1 month all scar scale measures were lower in treated areas, only the vascularity scale was significantly different between the two areas. After 4 months, all scale measures were significantly lower in the silicone gel group than in the control group, except for the pain score. Silicone gel is an effective treatment for hypertrophic burn scars.

Fibronectin EDA forms the chronic fibrotic scar after contusive spinal cord injury.

PubMed

Cooper, John G; Jeong, Su Ji; McGuire, Tammy L; Sharma, Sripadh; Wang, Wenxia; Bhattacharyya, Swati; Varga, John; Kessler, John A

2018-04-27

Gliosis and fibrosis after spinal cord injury (SCI) lead to formation of a scar that is an impediment to axonal regeneration. Fibrotic scarring is characterized by the accumulation of fibronectin, collagen, and fibroblasts at the lesion site. The mechanisms regulating fibrotic scarring after SCI and its effects on axonal elongation and functional recovery are not well understood. In this study, we examined the effects of eliminating an isoform of fibronectin containing the Extra Domain A domain (FnEDA) on both fibrosis and on functional recovery after contusion SCI using male and female FnEDA-null mice. Eliminating FnEDA did not reduce the acute fibrotic response but markedly diminished chronic fibrotic scarring after SCI. Glial scarring was unchanged after SCI in FnEDA-null mice. We found that FnEDA was important for the long-term stability of the assembled fibronectin matrix during both the subacute and chronic phases of SCI. Motor functional recovery was significantly improved, and there were increased numbers of axons in the lesion site compared to wildtype mice, suggesting that the chronic fibrotic response is detrimental to recovery. Our data provide insight into the mechanisms of fibrosis after SCI and suggest that disruption of fibronectin matrix stability by targeting FnEDA represents a potential therapeutic strategy for promoting recovery after SCI. Copyright © 2018 Elsevier Inc. All rights reserved.

The inflammatory response in myocardial injury, repair and remodeling

PubMed Central

Frangogiannis, Nikolaos G.

2015-01-01

Myocardial infarction triggers an intense inflammatory response that is essential for cardiac repair, but which is also implicated in the pathogenesis of post-infarction remodeling and heart failure. Signals in the infarcted myocardium activate toll-like receptor signalling, while complement activation and generation of reactive oxygen species induce cytokine and chemokine upregulation. Leukocytes recruited remove dead cells and matrix debris by phagocytosis, while setting the stage for scar formation. Timely repression of the inflammatory response is critical for effective healing and followed by activation of infarct myofibroblasts that secrete matrix proteins in the infarcted area. Members of the transforming growth factor-β family are critically involved in suppression of inflammation and activation of a pro-fibrotic program. Translation of these concepts in the clinic requires understanding of the pathophysiologic complexity and heterogeneity of post-infarction remodeling in human patients with myocardial infarction. Individuals with overactive and prolonged post-infarction inflammation might exhibit dilation and systolic dysfunction and benefit from targeted anti-IL-1 or anti-chemokine therapies, whereas patients with exaggerated fibrogenic reactions can develop diastolic heart failure and might require inhibition of the smad3 cascade. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to rationally implement inflammation-modulating strategies. PMID:24663091

Quantitative analysis of a scar's pliability, perfusion and metrology

NASA Astrophysics Data System (ADS)

Gonzalez, Mariacarla; Sevilla, Nicole; Chue-Sang, Joseph; Ramella-Roman, Jessica C.

2017-02-01

The primary effect of scarring is the loss of function in the affected area. Scarring also leads to physical and psychological problems that could be devastating to the patient's life. Currently, scar assessment is highly subjective and physician dependent. The examination relies on the expertise of the physician to determine the characteristics of the scar by touch and visual examination using the Vancouver scar scale (VSS), which categorizes scars depending on pigmentation, pliability, height and vascularity. In order to establish diagnostic guidelines for scar formation, a quantitative, accurate assessment method needs to be developed. An instrument capable of measuring all categories was developed; three of the aforementioned parameters will be explored. In order to look at pliability, a durometer which measures the amount of resistance a surface exerts to prevent the permanent indentation of the surface is used due to its simplicity and quantitative output. To look at height and vascularity, a profilometry system that collects the location of the scar in three-dimensions and laser speckle imaging (LSI), which shows the dynamic changes in perfusion, respectively, are used. Gelatin phantoms were utilized to measure pliability. Finally, dynamic changes in skin perfusion of volunteers' forearms undergoing pressure cuff occlusion were measured, along with incisional scars.

Prognostic Value of Myocardial Scarring on CMR in Patients With Cardiac Sarcoidosis.

PubMed

Coleman, G Cameron; Shaw, Peter W; Balfour, Pelbreton C; Gonzalez, Jorge A; Kramer, Christopher M; Patel, Amit R; Salerno, Michael

2017-04-01

This study sought to perform a systematic review and meta-analysis to understand the prognostic value of myocardial scarring as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging in patients with known or suspected cardiac sarcoidosis. Although CMR is increasingly used for the diagnosis of cardiac sarcoidosis, the prognostic value of CMR has been less well described in this population. PubMed, Cochrane CENTRAL, and metaRegister of Controlled Trials were searched for CMR studies with ≥1 year of prognostic data. Primary endpoints were all-cause mortality and a composite outcome of arrhythmogenic events (ventricular arrhythmia, implantable cardioverter-defibrillator shock, sudden cardiac death) plus all-cause mortality during follow-up. Summary effect estimates were generated with random-effects modeling. Ten studies were included, involving a total of 760 patients with a mean follow-up of 3.0 ± 1.1 years. Patients had a mean age of 53 years, 41% were male, 95.3% had known extracardiac sarcoidosis, and 21.6% had known cardiac sarcoidosis. The average ejection fraction was 57.8 ± 9.1%. Patients with LGE had higher odds for all-cause mortality (odds ratio [OR]: 3.06; p < 0.03) and higher odds of the composite outcome (OR: 10.74; p < 0.00001) than those without LGE. Patients with LGE had an increased annualized event rate of the composite outcome (11.9% vs. 1.1%; p < 0.0001). In patients with known or suspected cardiac sarcoidosis, the presence of LGE on CMR imaging is associated with increased odds of both all-cause mortality and arrhythmogenic events. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar.

PubMed

Ruiz-Villalba, Adrián; Simón, Ana M; Pogontke, Cristina; Castillo, María I; Abizanda, Gloria; Pelacho, Beatriz; Sánchez-Domínguez, Rebeca; Segovia, José C; Prósper, Felipe; Pérez-Pomares, José M

2015-05-19

Although efforts continue to find new therapies to regenerate infarcted heart tissue, knowledge of the cellular and molecular mechanisms involved remains poor. This study sought to identify the origin of cardiac fibroblasts (CFs) in the infarcted heart to better understand the pathophysiology of ventricular remodeling following myocardial infarction (MI). Permanent genetic tracing of epicardium-derived cell (EPDC) and bone marrow-derived blood cell (BMC) lineages was established using Cre/LoxP technology. In vivo gene and protein expression studies, as well as in vitro cell culture assays, were developed to characterize EPDC and BMC interaction and properties. EPDCs, which colonize the cardiac interstitium during embryogenesis, massively differentiate into CFs after MI. This response is disease-specific, because angiotensin II-induced pressure overload does not trigger significant EPDC fibroblastic differentiation. The expansion of epicardial-derived CFs follows BMC infiltration into the infarct site; the number of EPDCs equals that of BMCs 1 week post-infarction. BMC-EPDC interaction leads to cell polarization, packing, massive collagen deposition, and scar formation. Moreover, epicardium-derived CFs display stromal properties with respect to BMCs, contributing to the sustained recruitment of circulating cells to the damaged zone and the cardiac persistence of hematopoietic progenitors/stem cells after MI. EPDCs, but not BMCs, are the main origin of CFs in the ischemic heart. Adult resident EPDC contribution to the CF compartment is time- and disease-dependent. Our findings are relevant to the understanding of post-MI ventricular remodeling and may contribute to the development of new therapies to treat this disease. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Differential MR Delayed Enhancement Patterns of Chronic Myocardial Infarction between Extracellular and Intravascular Contrast Media

PubMed Central

Wang, Jian; Xiang, Bo; Lin, Hung Yu; Liu, Hongyu; Freed, Darren; Arora, Rakesh C.; Tian, Ganghong

2015-01-01

Objectives Because the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media. Materials and Methods Twenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson's trichrome method. Results Cine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn’t significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen. Conclusions Chronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn’t provide delayed enhancement. PMID:25816056

Current options for the treatment of pathological scarring.

PubMed

Poetschke, Julian; Gauglitz, Gerd G

2016-05-01

Scarring is the consequence of surgery, trauma or different skin diseases. Apart from fresh, immature scars,that transform into mature scars over the course of would healing and that do not require further treatment,linear hypertrophic scars, widespread hypertrophic scars, keloids and atrophic scars exist. Symptoms like pruritusand pain, stigmatization as well as functional and aesthetic impairments that are very disturbing for the affected patients can bethe basis for the desire for treatment. Today, a multitude of options for the treatment and prevention of scars exists. Topical agents based on silicone or onion extract, intralesional injections of cristalline glucocorticoids (oftentimes in combinationwith cryotherapy) or 5-Fluorouracil as well as ablative and nonablative laser treatment are used. Current guidelines summarize the multitude of available treatment options and the currently available datafor the treating physicians, allowing them to make clear therapy recommendations for every single scar type. Relieving patients of their discomfort and doing their aesthetic demands justice is thus possible. Apart from scar prevention becoming more and more important, the increased use of modernlaser treatment options constitutes a key point in clinical scar treatment. At the same time the attention is turned to evaluating current therapeutic options with the help of contemporary study designs so as to graduallyimprove the level of evidence in scar treatment. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Scar massage for hypertrophic burns scarring-A systematic review.

PubMed

Ault, P; Plaza, A; Paratz, J

2018-02-01

Scar massage is used in burn units globally to improve functional and cosmetic outcomes of hypertrophic scarring following a burn, however, the evidence to support this therapy is unknown. To review the literature and assess the efficacy of scar massage in hypertrophic burn scars. MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library were searched using the key words "burn", "burn injury", "thermal injury" and "scar", "hypertrophic scar" and "massage", "manipulation", "soft tissue mobilisation", "soft tissue manipulation". The articles were scored by the assessors using the Physiotherapy Evidence Database (PEDro) scale and outcome measures on range of motion (ROM), cosmesis (vascularity, pliability, height), pain scores, pruritus, and psychological measures of depression and anxiety were extracted. Eight publications were included in the review with 258 human participants and 15 animal subjects who received scar massage following a thermal injury resulting in hypertrophic scarring. Outcome measures that demonstrated that scar massage was effective included scar thickness as measured with ultrasonography (p=0.001; g=-0.512); depression (Centre for Epidemiologic Studies - Depression [CES-D]) (p=0.031; g=-0.555); pain as measured with Visual Analogue Scale (VAS) (p=0.000; g=-1.133) and scar characteristics including vascularity (p=0.000; g=-1.837), pliability (p=0.000; g=-1.270) and scar height (p=0.000; g=-2.054). Outcome measures that trended towards significance included a decrease in pruritus (p=0.095; g=-1.157). It appears that there is preliminary evidence to suggest that scar massage may be effective to decrease scar height, vascularity, pliability, pain, pruritus and depression in hypertrophic burns scaring. This review reflects the poor quality of evidence and lack of consistent and valid scar assessment tools. Controlled, clinical trials are needed to develop evidence-based guidelines for scar massage in hypertrophic burns scarring. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Long-Term Outcome of Administration of c-kitPOS Cardiac Progenitor Cells After Acute Myocardial Infarction: Transplanted Cells Do Not Become Cardiomyocytes, Structural and Functional Improvement and Proliferation of Endogenous Cells Persist for at Least One Year

PubMed Central

Tang, Xian-Liang; Li, Qianhong; Rokosh, Gregg; Sanganalmath, Santosh K.; Chen, Ning; Ou, Qinghui; Stowers, Heather; Hunt, Greg; Bolli, Roberto

2016-01-01

RATIONALE Cardiac progenitor cells (CPCs) improve left ventricular (LV) remodeling and function after acute or chronic myocardial infarction (MI). However, the long-term (>5 weeks) effects, potential tumorigenicity, and fate of transplanted CPCs are unknown. OBJECTIVE To assess the outcome of CPC therapy at 1 year. METHODS AND RESULTS Female rats underwent a 90-min coronary occlusion; 4 h after reperfusion, they received intracoronarily vehicle or 1 million male, syngeneic CPCs. One year later, CPC-treated rats exhibited smaller scars and more viable myocardium in the risk region, along with improved LV remodeling and regional and global LV function. No tumors were observed. Some transplanted (Y-chromosomePOS) CPCs (or their progeny) persisted and continued to proliferate, but they failed to acquire a mature cardiomyocyte phenotype and were too few (4-8% of nuclei) to account for the benefits of CPC therapy. Surprisingly, CPC transplantation triggered a prolonged proliferative response of endogenous cells, resulting in increased formation of endothelial cells and Y-chromosomeNEG CPCs for 12 months and increased formation, for at least 7 months, of small cells that expressed cardiomyocytic proteins (α-sarcomeric actin) but did not have a mature cardiomyocyte phenotype. CONCLUSIONS The beneficial effects of CPCs on LV remodeling and dysfunction are sustained for at least 1 year, and thus are likely to be permanent. Since transplanted CPCs do not differentiate into mature myocytes, their major mechanism of action must involve paracrine actions. These paracrine mechanisms could be very prolonged because some CPCs engraft, proliferate, and persist at 1 year. This is the first report that transplantation of any cell type in the heart induces a proliferative response that lasts at least 1 year. The results strongly support the safety and clinical utility of CPC therapy. PMID:26838790

Use of autologous fat grafting for the correction of burn scar contracture in the hand: a case report

PubMed Central

Al-Hayder, Shems; Gramkow, Christina; Trojahn Kølle, Stig-Frederik

2017-01-01

Abstract Severe burn injuries to the hand represent a topic of great concern due to long-term complications such as hypertrofic burn scar and contracture, which may result in loss of function. We present a case of burn scar contracture in the hand of a child undergoing Z-plasty and lipofilling. PMID:28971111

Recent Developments in the Use of Intralesional Injections Keloid Treatment

PubMed Central

Trisliana Perdanasari, Aurelia; Lazzeri, Davide; Su, Weijie; Xi, Wenjing; Zheng, Zhang; Ke, Li; Min, Peiru; Feng, Shaoqing; Persichetti, Paolo

2014-01-01

Keloid scars are often considered aesthetically unattractive and frustrating problems that occur following injuries. They cause functional and cosmetic deformities, displeasure, itching, pain, and psychological stress and possibly affect joint movement. The combination of these factors ultimately results in a compromised quality of life and diminished functional performance. Various methods have been implemented to improve keloid scars using both surgical and non-surgical approaches. However, it has proven to be a challenge to identify a universal treatment that can deliver optimal results for all types of scars. Through a PubMed search, we explored most of the literature that is available about the intralesional injection treatment of hypertrophic scars and keloids and highlights both current (corticosteroid, 5-fluorouracil, bleomycin, interferon, cryotherapy and verapamil) and future treatments (interleukin-10 and botulinum toxin type A). The reference lists of retrieved articles were also analysed. Information was gathered about the mechanism of each injection treatment, its benefits and associated adverse reactions, and possible strategies to address adverse reactions to provide reliable guidelines for determining the optimal treatment for particular types of keloid scars. This article will benefit practitioners by outlining evidence-based treatment strategies using intralesional injections for patients with hypertrophic scars and keloids. PMID:25396172

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

PubMed

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2013-10-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction.

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

PubMed Central

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2014-01-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns

PubMed Central

Castleberry, Steven A.; Golberg, Alexander; Sharkh, Malak Abu; Khan, Saiqa; Almquist, Benjamin D.; Austen, William G.; Yarmush, Martin L.; Hammond, Paula T.

2017-01-01

Wound healing is an incredibly complex biological process that often results in thickened collagen-enriched healed tissue called scar. Cutaneous scars lack many functional structures of the skin such as hair follicles, sweat glands, and papillae. The absence of these structures contributes to a number of the long-term morbidities of wound healing, including loss of function for tissues, increased risk of re-injury, and aesthetic complications. Scar formation is a pervasive factor in our daily lives; however, in the case of serious traumatic injury, scars can create long-lasting complications due to contraction and poor tissue remodeling. Within this report we target the expression of connective tissue growth factor (CTGF), a key mediator of TGFβ pro-fibrotic response in cutaneous wound healing, with controlled local delivery of RNA interference. Through this work we describe both a thorough in vitro analysis of nanolayer coated sutures for the controlled delivery of siRNA and its application to improve scar outcomes in a third-degree burn induced scar model in rats. We demonstrate that the knockdown of CTGF significantly altered the local expression of αSMA, TIMP1, and Col1a1, which are known to play roles in scar formation. The knockdown of CTGF within the healing burn wounds resulted in improved tissue remodeling, reduced scar contraction, and the regeneration of papillary structures within the healing tissue. This work adds support to a number of previous reports that indicate CTGF as a potential therapeutic target for fibrosis. Additionally, we believe that the controlled local delivery of siRNA from ultrathin polymer coatings described within this work is a promising approach in RNA interference that could be applied in developing improved cancer therapies, regenerative medicine, and fundamental scientific research. PMID:27108403

[Psychological stress and sudden death].

PubMed

Pignalberi, Carlo; Ricci, Renato; Santini, Massimo

2002-10-01

Recent studies provide relevant evidence that psychological stress significantly influences the pathogenesis of sudden cardiac death. Psychological stress expresses a situation of imbalance, derived from a real or perceived disparity between environmental demands and the individual's ability to cope with these demands. A situation of psychological stress may include different components: personality factors and character traits, anxiety and depression, social isolation and acute or chronic adverse life events. In particular, it has been documented that a sudden extremely hard event, such as an earthquake or a war strike, can significantly increase the incidence of sudden death. Nevertheless, each one of these factors, if not present, can balance a partially unfavorable situation; this overview suggests a multifactorial situation where almost all elements are present and in which the relative influence of each one varies according to the individual examined. Sudden death occurs when a transient disruption (such as acute myocardial ischemia, platelet activation or neuroendocrine variations), occurring in a patient with a diseased myocardium (such as one with a post-necrotic scar or hypertrophy), triggers a malignant arrhythmia. Psychological stress acts at both levels: by means of a "chronic" action it contributes to create the myocardial background, while by means of an acute action it can create the transient trigger precipitating sudden death. In the chronic action two possible mechanisms can be detected: the first is a direct interaction, which contributes to cause a hypertension status or to exacerbate coronary atherosclerosis consequent to endothelial dysfunction; the second one acts through adverse health behaviors, such as a poor diet, alcohol consumption or smoking. In case of acute psychological stress, the mechanisms involved are mainly the ability to trigger myocardial ischemia, to promote arrhythmogenesis, to stimulate platelet function, and to increase blood viscosity. Finally, some individuals have a sympathetic nervous system hyper-responsitivity, manifesting as exaggerated heart rate and blood pressure responses which result in accelerated atherosclerosis.

Development and Implementation of Discrete Polymeric Microstructural Cues for Applications in Cardiac Tissue Engineering

NASA Astrophysics Data System (ADS)

Pinney, James Richardson

Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. Despite care in the acute setting of MI, subsequent development of scar tissue and a lack of treatments for this maladaptive response lead to a poor prognosis. This has increased burdens on the cost of healthcare due to chronic disability. Here a novel therapeutic strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructural cues to attenuate the fibrotic response and improve functional outcomes is presented. Additionally, applications of integrated chemical functionalizations into discrete, micro-scale polymer structures are discussed in the realm of tissue engineering in order to impart enhancements in in vivo localization, three-dimensional manipulation and drug delivery. Polymeric microstructures, termed "microrods" and "microcubes", were fabricated using photolithographic techniques and studied in three-dimensional culture models of the fibrotic environment and by direct injection into the infarct zone of adult Sprague-Dawley rats. In vitro gene expression and functional and histological results were analyzed, showing a dose-dependent down-regulation fibrotic indicators and improvement in cardiac function. Furthermore, iron oxide nanoparticles and functionalized fluorocarbons were incorporated into the polymeric microdevices to promote in situ visualization by magnetic resonance imaging as well as to facilitate the manipulation and alignment of microstructural cues in a tissue-realistic environment. Lastly, successful encapsulation of native MGF peptide within microrods is demonstrated with release over two weeks as a proof of concept in the ability to locally deliver myogenic or supportive pharmacotherapeutics to the injured myocardium. This work demonstrates the efficacy and versatility of discrete microtopographical cues to attenuate the fibrotic response after MI and suggests a novel therapeutic strategy for combatting the chronic sequelae of pathologic fibrosis that is biocompatible, localizable, functionalizable, and biologically, mechanically, and chemically active. By integrating this multifunctional strategy into post-infarctive care, as well as a wide range of other fibrotic and mechanically sensitive disease processes, more directed and effective therapeutics could be developed to aid in combatting these complex and challenging pathologies.

Stem cells for cardiac repair: problems and possibilities.

PubMed

Henning, Robert J

2013-11-01

Ischemic heart disease is a major cause of death throughout the world. In order to limit myocardial damage and possibly generate new myocardium, stem cells are currently being injected into patients with ischemic heart disease. Three major patient investigations, The LateTIME, the TIME and the Swiss Myocardial Infarction trials, have recently addressed the questions of whether progenitor cells from unfractionated bone marrow mononuclear cells limit myocardial damage and what the optimal time to inject these cells after acute myocardial infarctions (AMIs) is. In each of these trials, there were no significant differences between treated and control patients when bone marrow cells were administered 5-7 days or 2-3 weeks after AMIs. Nevertheless, these investigations provide important information regarding clinical trial designs. Patients with AMIs in these trials were treated with percutaneous coronary intervention within a median of 4-5 h after the onset of chest pain. Thereafter, all patients received guideline-guided optimal medical therapy. Consequently, the sizes of AMIs were significantly limited. In patients with small AMIs and near-normal left ventricular ejection fractions, progenitor cells are least effective. However, these trials do question whether autologous bone marrow mononuclear cells are the optimal cells for myocardial repair owing to low numbers of progenitor cells in bone marrow aspirates and the significant variability in potency and efficacy of these cells in patients with chronic multisystem diseases. In contrast, the SCIPIO and the CAUDUCEUS trials examined cardiac progenitor cells in patients with ischemic cardiomyopathies. These trials reported over 1-2 years that cardiac progenitor cells produced significant improvements in left ventricular contractility due to 12-24 g decreases in myocardial scars and 18-23 g increases in viable myocardial muscle. However, caution must be exercised in the interpretation of these studies due to the small numbers of highly selected patients and intra- and inter-observer variability in infarct size measurements. Anatomical and histological examinations of large numbers of patients treated with these cells are necessary to confirm significant generation of myocytes and decreases in infarct size and fibrosis.

Testing the Vulnerability and Scar Models of Self-Esteem and Depressive Symptoms from Adolescence to Middle Adulthood and across Generations

ERIC Educational Resources Information Center

Steiger, Andrea E.; Fend, Helmut A.; Allemand, Mathias

2015-01-01

The vulnerability model states that low self-esteem functions as a predictor for the development of depressive symptoms whereas the scar model assumes that these symptoms leave scars in individuals resulting in lower self-esteem. Both models have received empirical support, however, they have only been tested within individuals and not across…

Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus.

PubMed

Chin, Calvin W L; Chin, Chee-Yang; Ng, Marie X R; Le, Thu-Thao; Huang, Fei-Qiong; Fong, Kok-Yong; Thumboo, Julian; Tan, Ru-San

2014-09-01

Endothelial dysfunction is associated with traditional and systemic lupus erythematosus (SLE)-specific risk factors, and early data suggest reversibility of endothelial dysfunction with therapy. The clinical relevance of endothelial function assessment has been limited by the lack of studies, demonstrating its prognostic significance and impact on early myocardial function. Therefore, we aimed to determine the association between endothelial and myocardial diastolic function in SLE women. Women with SLE and no coronary artery disease were prospectively recruited and underwent radionuclide myocardial perfusion imaging (MPI) (Jetstream, Philips, the Netherlands) to exclude subclinical myocardial ischemia. Cardiac and vascular functions were assessed in all patients (Alpha 10, Aloka, Tokyo). Diastolic function was assessed using pulse wave early (E) and late mitral blood inflow and myocardial tissue Doppler (mean of medial and lateral annulus e') velocities. Endothelial function was measured using brachial artery flow-mediated vasodilatation (FMD%). Univariate and multivariate linear regressions were used to assess the association between FMD% and myocardial diastolic function, adjusting for potential confounders. Thirty-eight patients without detectable myocardial ischemia on MPI were studied (mean age 44 ± 10 years; mean disease duration 14 ± 6 years). About 61 % of patients had normal diastolic function (E/e' ≤ 8), and 5 % of patients had definite diastolic dysfunction with E/e' > 13 (mean 7.1 ± 2.9). FMD% was associated with E/e' (regression coefficient β = -0.35; 95 % CI -0.62 to -0.08; p = 0.01) independent of systolic blood pressure, age, and SLICC/ACR Damage Index.

Association analysis of CYP2C9*3 and phenytoin-induced severe cutaneous adverse reactions (SCARs) in Thai epilepsy children.

PubMed

Suvichapanich, Supharat; Jittikoon, Jiraphun; Wichukchinda, Nuanjun; Kamchaisatian, Wasu; Visudtibhan, Anannit; Benjapopitak, Suwat; Nakornchai, Somjai; Manuyakorn, Wiparat; Mahasirimongkol, Surakameth

2015-08-01

CYP2C9 is the key enzyme in aromatic antiepileptic drugs (AEDs) metabolism. CYP2C9*3 is a loss of function polymorphism. This study was designed to investigate genetic association between CYP2C9*3 and aromatic AED-induced severe cutaneous adverse reactions (SCARs) in Thai children. The 37 aromatic AED-induced SCARs patients (20 phenobarbital and 17 phenytoin) and 35 tolerances (19 phenobarbital and 16 phenytoin) were enrolled. CYP2C9*3 was genotyped by allele-specific PCRs. The association between CYP2C9*3 with phenytoin-induced SCARs and phenobarbital-induced SCARs were analyzed in comparison with tolerances and healthy samples. Significant association between phenytoin-induced SCARs and CYP2C9*3 was discovered (odds ratio=14.52; 95% confidence interval (CI)=1.18-∞, P-value=0.044). CYP2C9*3 was not associated with phenobarbital-induced SCARs. This study is the first report of CYP2C9*3 association to phenytoin-induced SCARs in Thai epileptic children. The CYP2C9*3 is a reasonable predictive genetic marker to anticipate SCARs from phenytoin.

Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions.

PubMed

Marshall, Clement D; Hu, Michael S; Leavitt, Tripp; Barnes, Leandra A; Lorenz, H Peter; Longaker, Michael T

2018-02-01

Significance: Scarring of the skin from burns, surgery, and injury constitutes a major burden on the healthcare system. Patients affected by major scars, particularly children, suffer from long-term functional and psychological problems. Recent Advances: Scarring in humans is the end result of the wound healing process, which has evolved to rapidly repair injuries. Wound healing and scar formation are well described on the cellular and molecular levels, but truly effective molecular or cell-based antiscarring treatments still do not exist. Recent discoveries have clarified the role of skin stem cells and fibroblasts in the regeneration of injuries and formation of scar. Critical Issues: It will be important to show that new advances in the stem cell and fibroblast biology of scarring can be translated into therapies that prevent and reduce scarring in humans without major side effects. Future Directions: Novel therapies involving the use of purified human cells as well as agents that target specific cells and modulate the immune response to injury are currently undergoing testing. In the basic science realm, researchers continue to refine our understanding of the role that particular cell types play in the development of scar.

Arrhythmogenic right ventricular cardiomyopathy mimics: role of cardiovascular magnetic resonance

PubMed Central

2013-01-01

Background Cardiovascular magnetic resonance (CMR) is commonly used in patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) based on ECG, echocardiogram and Holter. However, various diseases may present with clinical characteristics resembling ARVC causing diagnostic dilemmas. The aim of this study was to explore the role of CMR in the differential diagnosis of patients with suspected ARVC. Methods 657 CMR referrals suspicious for ARVC in a single tertiary referral centre were analysed. Standardized CMR imaging protocols for ARVC were performed. Potential ARVC mimics were grouped into: 1) displacement of the heart, 2) right ventricular overload, and 3) non ARVC-like cardiac scarring. For each, a judgment of clinical impact was made. Results Twenty patients (3.0%) fulfilled imaging ARVC criteria. Thirty (4.6%) had a potential ARVC mimic, of which 25 (3.8%) were considered clinically important: cardiac displacement (n=17), RV overload (n=7) and non-ARVC like myocardial scarring (n=4). One patient had two mimics; one patient had dual pathology with important mimic and ARVC. RV overload and scarring conditions were always thought clinically important whilst the importance of cardiac displacement depended on the degree of displacement from severe (partial absence of pericardium) to epiphenomenon (minor kyphoscoliosis). Conclusions Some patients referred for CMR with suspected ARVC fulfil ARVC imaging criteria (3%) but more have otherwise unrecognised diseases (4.6%) mimicking potentially ARVC. Clinical assessment should reflect this, emphasising the assessment and/or exclusion of potential mimics in parallel with the detection of ARVC major and minor criteria. PMID:23398958

A Modeling Approach for Burn Scar Assessment Using Natural Features and Elastic Property

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsap, L V; Zhang, Y; Goldgof, D B

2004-04-02

A modeling approach is presented for quantitative burn scar assessment. Emphases are given to: (1) constructing a finite element model from natural image features with an adaptive mesh, and (2) quantifying the Young's modulus of scars using the finite element model and the regularization method. A set of natural point features is extracted from the images of burn patients. A Delaunay triangle mesh is then generated that adapts to the point features. A 3D finite element model is built on top of the mesh with the aid of range images providing the depth information. The Young's modulus of scars ismore » quantified with a simplified regularization functional, assuming that the knowledge of scar's geometry is available. The consistency between the Relative Elasticity Index and the physician's rating based on the Vancouver Scale (a relative scale used to rate burn scars) indicates that the proposed modeling approach has high potentials for image-based quantitative burn scar assessment.« less

Imaging of Myocardial Fatty Acid Oxidation

PubMed Central

Mather, Kieren J; DeGrado, Tim

2016-01-01

Myocardial fuel selection is a key feature of the health and function of the heart, with clear links between myocardial function and fuel selection and important impacts of fuel selection on ischemia tolerance. Radiopharmaceuticals provide uniquely valuable tools for in vivo, non-invasive assessment of these aspects of cardiac function and metabolism. Here we review the landscape of imaging probes developed to provide noninvasive assessment of myocardial fatty acid oxidation (MFAO). Also, we review the state of current knowledge that myocardial fatty acid imaging has helped establish of static and dynamic fuel selection that characterizes cardiac and cardiometabolic disease and the interplay between fuel selection and various aspects of cardiac function. PMID:26923433

Magnetic Resonance Imaging (MRI) for the Assessment of Myocardial Viability

PubMed Central

2010-01-01

Executive Summary In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of noninvasive cardiac imaging modalities. After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography. A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed. A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website). The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis Magnetic Resonance Imaging for the Assessment of Myocardial Viability: An Evidence-Based Analysis Objective The objective of this analysis is to assess the effectiveness and cost-effectiveness of cardiovascular magnetic resonance imaging (cardiac MRI) for the assessment of myocardial viability. To evaluate the effectiveness of cardiac MRI viability imaging, the following outcomes were examined: the diagnostic accuracy in predicting functional recovery and the impact of cardiac MRI viability imaging on prognosis (mortality and other patient outcomes). Clinical Need: Condition and Target Population Left Ventricular Systolic Dysfunction and Heart Failure Heart failure is a complex syndrome characterized by the heart’s inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) 1 is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. Treatment Options In general, there are three options for the treatment of heart failure: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or, in some cases, through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure. Myocardial Viability Left ventricular dysfunction may be permanent, due to the formation of myocardial scar, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically: dobutamine echocardiography (echo), stress echo with contrast, SPECT using either technetium or thallium, cardiac magnetic resonance imaging (cardiac MRI), and positron emission tomography (PET). Dobutamine Echocardiography Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 – 10 µg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Stress Echocardiography with Contrast Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Cardiac Positron Emission Tomography Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite directions (180 degrees) and captured by an external array of detector elements in the PET gantry. Computer software is then used to convert the radiation emission into images. The system is set up so that it only detects coincident gamma rays that arrive at the detectors within a predefined temporal window, while single photons arriving without a pair or outside the temporal window do not active the detector. This allows for increased spatial and contrast resolution. Cardiac Magnetic Resonance Imaging Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery. Evidence-Based Analysis Research Questions What is the diagnostic accuracy of cardiac MRI for detecting myocardial viability? What is the impact of cardiac MRI viability imaging on prognosis (mortality and other clinical outcomes)? How does cardiac MRI compare with cardiac PET imaging for the assessment of myocardial viability? What is the contribution of cardiac MRI viability imaging to treatment decision making? Is cardiac MRI cost-effective compared with other cardiac imaging modalities for the assessment of myocardial viability? Literature Search A literature search was performed on October 9, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 until October 9, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. In addition, published systematic reviews and health technology assessments were reviewed for relevant studies published before 2005. Reference lists were also examined for any additional relevant studies not identified through the search. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Inclusion Criteria English language full-reports Published between January 1, 2005 and October 9, 2009 Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies Patients with chronic, known coronary artery disease (CAD) Used contrast-enhanced MRI Assessment of functional recovery ≥ 3 months after revascularization Exclusion Criteria < 20 patients < 18 years of age Patients with non-ischemic heart disease Studies conducted exclusively in patients with acute myocardial infarction (MI) Studies where TP, TN, FP, FN cannot be determined Outcomes of Interest Sensitivity Specificity Positive predictive value (PPV) Negative Predictive value (NPV) Positive likelihood ratio Negative likelihood ratio Diagnostic accuracy Mortality rate (for prognostic studies) Adverse events Summary of Findings Based on the available very low quality evidence, MRI is a useful imaging modality for the detection of viable myocardium. The pooled estimates of sensitivity and specificity for the prediction of regional functional recovery as a surrogate for viable myocardium are 84.5% (95% CI: 77.5% – 91.6%) and 71.0% (95% CI: 68.8% – 79.2%), respectively. Subgroup analysis demonstrated a statistically significant difference in the sensitivity of MRI to assess myocardial viability for studies using ≤25% hyperenhancement as a viability threshold versus studies using ≤50% hyperenhancement as their viability threshold [78.7 (95% CI: 69.1% - 88.2%) and 96.2 (95% CI: 91.8 – 100.6); p=0.0044 respectively]. Marked differences in specificity were observed [73.6 (95% CI: 62.6% - 84.6%) and 47.2 (95% CI: 22.2 – 72.3); p=0.2384 respectively]; however, these findings were not statistically significant. There were no statistically significant differences between the sensitivities or specificities for any other subgroups including mean preoperative LVEF, imaging method for function recovery assessment, and length of follow-up. There was no evidence available to determine whether patients with viable myocardium who are revascularized have a lower mortality rate than those who are treated with medical therapy. PMID:23074392

Learning from regeneration research organisms: The circuitous road to scar free wound healing

PubMed Central

Erickson, Jami R.; Echeverri, Karen

2018-01-01

The skin is the largest organ in the body and plays multiple essential roles ranging from regulating temperature, preventing infection and ultimately defining who we are physically. It is a highly dynamic organ that constantly replaces the outermost cells throughout life. However, when faced with a major injury, human skin cannot restore a significant lesion to its original functionality, instead a reparative scar is formed. In contrast to this, many other species have the unique ability to regenerate full thickness skin without formation of scar tissue. Here we review recent advances in the field that shed light on how the skin cells in regenerative species react to injury to prevent scar formation versus scar forming humans. PMID:29179946

Molecular requirements for actin-based lamella formation in Drosophila S2 cells

PubMed Central

Rogers, Stephen L.; Wiedemann, Ursula; Stuurman, Nico; Vale, Ronald D.

2003-01-01

Cell migration occurs through the protrusion of the actin-enriched lamella. Here, we investigated the effects of RNAi depletion of ∼90 proteins implicated in actin function on lamella formation in Drosophila S2 cells. Similar to in vitro reconstitution studies of actin-based Listeria movement, we find that lamellae formation requires a relatively small set of proteins that participate in actin nucleation (Arp2/3 and SCAR), barbed end capping (capping protein), filament depolymerization (cofilin and Aip1), and actin monomer binding (profilin and cyclase-associated protein). Lamellae are initiated by parallel and partially redundant signaling pathways involving Rac GTPases and the adaptor protein Nck, which stimulate SCAR, an Arp2/3 activator. We also show that RNAi of three proteins (kette, Abi, and Sra-1) known to copurify with and inhibit SCAR in vitro leads to SCAR degradation, revealing a novel function of this protein complex in SCAR stability. Our results have identified an essential set of proteins involved in actin dynamics during lamella formation in Drosophila S2 cells. PMID:12975351

TRPV3 Channel in Keratinocytes in Scars with Post-Burn Pruritus

PubMed Central

Park, Chun Wook; Kim, Hyun Ji; Choi, Yong Won; Chung, Bo Young; Woo, So-Youn; Song, Dong-Keun; Kim, Hye One

2017-01-01

Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of protease-activated receptor 2 (PAR2) and transient receptor potential vanniloid 3 (TRPV3), along with the relation of TRPV3 to thymic stromal lymphopoietin (TSLP). Specimens from normal (unscarred) or burn-scarred (with or without pruritus) tissue were obtained from burn patients for this study. In each sample, the keratinocytes were isolated and cultured, and the intracellular Ca2+ level at the time of stimulation of each factor was quantified and the interaction was screened. PAR2 function was reduced by antagonism of TRPV3. Inhibiting protein kinase A (PKA) and protein kinase C (PKC) reduced TRPV3 function. TSLP mRNA and protein, and TSLPR protein expressions, increased in scars with post-burn pruritus, compared to scars without it or to normal tissues. In addition, TRPV1 or TRPV3 activation induced increased TSLP expression. Conclusively, TRPV3 may contribute to pruritus in burn scars through TSLP, and can be considered a potential therapeutic target for post-burn pruritus. PMID:29140280

Psychological status as a function of residual scarring and facial asymmetry after surgical repair of cleft lip and palate.

PubMed

Millar, Keith; Bell, Aileen; Bowman, Adrian; Brown, Denise; Lo, Tsz-Wai; Siebert, Paul; Simmons, David; Ayoub, Ashraf

2013-03-01

Objective : Objective measure of scarring and three-dimensional (3D) facial asymmetry after surgical correction of unilateral cleft lip (UCL) and unilateral cleft lip (UCLP). It was hypothesized that the degree of scarring or asymmetry would be correlated with poorer psychological function. Design : In a cross-sectional design, children underwent 3D imaging of the face and completed standardized assessments of self-esteem, depression, and state and trait anxiety. Parents rated children's adjustment with a standard scale. Setting : Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences. Patients : Fifty-one children aged 10 years with UCLP and 43 with UCL were recruited from the cohort treated with the surgical protocol of the CLEFTSIS managed clinical network in Scotland. Methods : Objective assessment to determine the luminance and redness of the scar and facial asymmetry. Depression, anxiety, and a self-esteem assessment battery were used for the psychological analysis. Results : Cleft cases showed superior psychological adjustment when compared with normative data. Prevalence of depression matched the population norm. The visibility of the scar (luminance ratio) was significantly correlated with lower self-esteem and higher trait anxiety in UCLP children (P  =  .004). Similar but nonsignificant trends were seen in the UCL group. Parental ratings of poorer adjustment also correlated with greater luminance of the scar. Conclusions : The objectively defined degree of postoperative cleft scarring was associated with subclinical symptoms of anxiety, depression, and low self-esteem.

Deterministic Encapsulation of Human Cardiac Stem Cells in Variable Composition Nanoporous Gel Cocoons To Enhance Therapeutic Repair of Injured Myocardium.

PubMed

Kanda, Pushpinder; Alarcon, Emilio I; Yeuchyk, Tanya; Parent, Sandrine; de Kemp, Robert A; Variola, Fabio; Courtman, David; Stewart, Duncan J; Davis, Darryl R

2018-04-20

Although cocooning explant-derived cardiac stem cells (EDCs) in protective nanoporous gels (NPGs) prior to intramyocardial injection boosts long-term cell retention, the number of EDCs that finally engraft is trivial and unlikely to account for salutary effects on myocardial function and scar size. As such, we investigated the effect of varying the NPG content within capsules to alter the physical properties of cocoons without influencing cocoon dimensions. Increasing NPG concentration enhanced cell migration and viability while improving cell-mediated repair of injured myocardium. Given that the latter occurred with NPG content having no detectable effect on the long-term engraftment of transplanted cells, we found that changing the physical properties of cocoons prompted explant-derived cardiac stem cells to produce greater amounts of cytokines, nanovesicles, and microRNAs that boosted the generation of new blood vessels and new cardiomyocytes. Thus, by altering the physical properties of cocoons by varying NPG content, the paracrine signature of encapsulated cells can be enhanced to promote greater endogenous repair of injured myocardium.

Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy.

PubMed

Hensley, Michael Taylor; Tang, Junnan; Woodruff, Kathleen; Defrancesco, Teresa; Tou, Sandra; Williams, Christina M; Breen, Mathew; Meurs, Kathryn; Keene, Bruce; Cheng, Ke

2017-08-01

Cardiosphere-derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non-ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c-kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Smart, Injury-Triggered Therapy for Ocular Trauma

DTIC Science & Technology

2016-10-01

prognosis due to retinal cell death , scar formation, and lack of functional regeneration. Proliferative vitreoretinopathy (PVR), a form of intraocular...Proteases, Metalloproteinases, Cell death , Gene Therapy 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME...vision has a poor prognosis due to retinal cell death , scar formation, and lack of functional regeneration. Proliferative vitreoretinopathy (PVR), a

Colloidal gas aphron foams: A novel approach to a hydrogel based tissue engineered myocardial patch

NASA Astrophysics Data System (ADS)

Johnson, Elizabeth Edna

Cardiovascular disease currently affects an estimated 58 million Americans and is the leading cause of death in the US. Over 2.3 million Americans are currently living with heart failure a leading cause of which is acute myocardial infarction, during which a part of the heart muscle is damaged beyond repair. There is a great need to develop treatments for damaged heart tissue. One potential therapy involves replacement of nonfunctioning scar tissue with a patch of healthy, functioning tissue. A tissue engineered cardiac patch would be ideal for such an application. Tissue engineering techniques require the use of porous scaffolds, which serve as a 3-D template for initial cell attachment and grow-th leading to tissue formation. The scaffold must also have mechanical properties closely matching those of the tissues at the site of implantation. Our research presents a new approach to meet these design requirements. A unique interaction between poly(vinyl alcohol) and amino acids has been discovered by our lab, resulting in the production of novel gels. These unique synthetic hydrogels along with one natural hydrogel, alginate (derived from brown seaweed), have been coupled with a new approach to tissue scaffold fabrication using solid colloidal gas aphrons (CGAs). CGAs are colloidal foams containing uniform bubbles with diameters on the order of micrometers. Upon solidification the GCAs form a porous, 3-D network suitable for a tissue scaffold. The project encompasses four specific aims: (I) characterize hydrogel formation mechanism, (II) use colloidal gas aphrons to produce hydrogel scaffolds, (III) chemically and physically characterize scaffold materials and (IV) optimize and evaluate scaffold biocompatibility.

Abnormal mitochondrial respiration in failed human myocardium.

PubMed

Sharov, V G; Todor, A V; Silverman, N; Goldstein, S; Sabbah, H N

2000-12-01

Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n=9) or idiopathic dilated (IDC, n=9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON). Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V(SUB)), state 3 respiration (after addition of ADP, V(ADP)) and respiration after the addition of atractyloside (V(AT)) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V(ADP)was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V(ADP)/V(AT), was also significantly decreased in HF compared to CON. In both ICM and IDC, V(ADP)was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance. Copyright 2000 Academic Press.

Targeting inflammatory pathways in myocardial infarction

PubMed Central

Christia, Panagiota; Frangogiannis, Nikolaos G

2013-01-01

Acute cardiomyocyte necrosis in the infarcted heart generates Damage-Associated Molecular Patterns (DAMPs), activating complement and Toll-Like Receptor (TLR)/Interleukin (IL)-1 signaling, and triggering an intense inflammatory reaction. Infiltrating leukocytes clear the infarct from dead cells, while activating reparative pathways that lead to formation of a scar. As the infarct heals the ventricle remodels; the geometric, functional and molecular alterations associated with post-infarction remodeling are driven by the inflammatory cascade and are involved in the development of heart failure. Because unrestrained inflammation in the infarcted heart induces matrix degradation and cardiomyocyte apoptosis, timely suppression of the post-infarction inflammatory reaction may be crucial to protect the myocardium from dilative remodeling and progressive dysfunction. Inhibition and resolution of post-infarction inflammation involves mobilization of inhibitory mononuclear cell subsets and requires activation of endogenous STOP signals. Our manuscript discusses the basic cellular and molecular events involved in initiation, activation and resolution of the post-infarction inflammatory response, focusing on identification of therapeutic targets. The failure of anti-integrin approaches in patients with myocardial infarction and a growing body of experimental evidence suggest that inflammation may not increase ischemic cardiomyocyte death, but accentuates matrix degradation causing dilative remodeling. Given the pathophysiologic complexity of post-infarction remodeling, personalized biomarker-based approaches are needed to target patient subpopulations with dysregulated inflammatory and reparative responses. Inhibition of pro-inflammatory signals (such as IL-1 and Monocyte Chemoattractant Protein-1) may be effective in patients with defective resolution of post-infarction inflammation who exhibit progressive dilative remodeling. In contrast, patients with predominant hypertrophic/fibrotic responses may benefit from anti-TGF strategies. PMID:23772948

Measuring the impact of burn scarring on health-related quality of life: Development and preliminary content validation of the Brisbane Burn Scar Impact Profile (BBSIP) for children and adults.

PubMed

Tyack, Zephanie; Ziviani, Jenny; Kimble, Roy; Plaza, Anita; Jones, Amber; Cuttle, Leila; Simons, Megan

2015-11-01

No burn-scar specific, health-related quality of life (HRQOL) measure exists. This study aimed to develop a patient-reported, evaluative HRQOL measure to assess the impact of burn scarring in children and adults. Semi-structured interviews, content validation surveys, and cognitive interviews were used to develop and test content validity of a new measure - the Brisbane Burn Scar Impact Profile (BBSIP). Participants comprised Australian adults (n=23) and children (n=19) with burn scarring; caregivers of children with burn scarring (n=28); and international scar management experts (n=14). Items distinct from other burn scar measures emerged. Four versions of the BBSIP were developed; one for children aged 8-18 years, one for adults, one for caregivers (as proxies for children aged less than 8-years), and one for caregivers of children aged 8-18 years. Preliminary content validity of the BBSIP was supported. Final items covered physical and sensory symptoms; emotional reactions; impact on social functioning and daily activities; impact of treatment; and environmental factors. The BBSIP was developed to assess burn-scar specific HRQOL and will be available at http://www.coolburns.com.au under a creative commons license. Further testing is underway. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Retrospective analysis of factors affecting the efficacy of surgical treatment of the scar.

PubMed

Yang, Z; Shi, X; Zhang, Y; Wang, S; Lei, Z; Liu, X; Fan, D

2014-04-01

The scar is a major problem in the medical profession. Its timely treatment is very important for the better outcome of the scar treatment and for the improvement of the life quality of the patients. The aim of this study was retrospectively analyzed the epidemiological characteristics affecting the efficacy of the scar surgical treatment of the people in the western part of China. Total 414 scar cases were retrospectively analyzed to clarify the epidemiological characteristics and the factors affecting the scar surgical treatment efficacy. The factors included were sex, age, area distribution, treatment seasons, injury sites, injury causes, and the time from scarring to the surgical treatment. All scar cases were surgically treated with the repairing technology including skin graft, flap and soft tissue dilation. There were 206 males and 208 females with the average age 20.53±12.9 years (age range 1-68 years). The patient proportions in the age groups of 0-20, 21-40 and >40 years were 61.4% (254 cases), 29.2% (121 cases), and 9.4% (39 cases) respectively. The patient's attendance rate reached the highest during the summer and winter. Most patients were from the rural areas with an increasing tendency each year. The burn scars were the most abundant and the injury sites were mostly the head and face. Univariate analysis showed that the time from scarring to the surgical treatment and the injury sites were significantly influenced the scar surgical treatment efficacy. Logistic regression analysis demonstrated that the injured sites of the head and face significantly influenced the scar surgical treatment efficacy. With the development of economy in China, more scar patients especially younger and children visit doctors predominantely from the rural areas. Usually, they get their scars in the exposed area of their bodies (head and face) which seriously affect the patient's appearance and function. Factors influencing the scar surgical treatment efficacy has important clinical significance of prevention and treatment.

Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium.

PubMed

Elmadbouh, I; Haider, Husnain Kh; Jiang, Shujia; Idris, Niagara Muhammad; Lu, Gang; Ashraf, Muhammad

2007-04-01

We aimed to optimize non-viral transfection of human stromal cell derived factor (SDF-1alpha) gene into skeletal myoblasts (SkM) and, transplant these cells to establish transient SDF-1alpha gradient to favor extra-cardiac stem cell translocation into infarcted heart. Optimized conditions for transfection of SDF-1alpha gene into syngenic SkM were achieved using FuGene6/phSDF-1alpha (3:2v/w, 4 h transfection) with 125 microM ZnCl(2) (p<0.001). After characterization for transgene overexpression by immunostaining, ELISA and PCR, the cells were transplanted in female rat model of myocardial infarction. Thirty-six rats were grouped (n=12/group) to receive 70 microl DMEM without cells (group-1) or containing 1.5 x 10(6) non-transfected (group-2) or SDF-1alpha transfected SkM (group-3). On day 4 post-transplantation (in 4 animals/group), marked expression of SDF-1alpha/sry-gene (p=0.003), total Akt, phospho-Akt and Bcl2 was observed in group-3. The number of CD31(+), C-kit(+) and CD34(+) cells was highest in group-3 hearts (p<0.01). Blood vessel density in group-3 was higher in both scar and peri-scar regions (p<0.001) as compared with other groups. Echocardiography showed improved indices of left ventricle contractile function and remodeling in group-3 (p<0.05) as compared with groups-1 and -2. We conclude that ex vivo SDF-1alpha transgene delivery promotes stem and progenitor cell migration to the heart, activates cell survival signaling and enhances angiomyogenesis in the infarcted heart.

Takotsubo-like syndrome triggered by fludrocortisone overdose for Addison's disease: a case report.

PubMed

Campean, Radu; Hasun, Matthias; Stöllberger, Claudia; Bucher, Johannes; Finsterer, Josef; Schnack, Christoph; Weidinger, Franz

2016-10-12

Reversible left ventricular dysfunction, also termed Takotsubo cardiomyopathy, is rarely reported in Addison's disease after initiation of hormone replacement therapy. The pathogenesis of this cardiomyopathy is unknown. A 41-year-old white woman with a history of autoimmune Hashimoto thyroiditis diagnosed 3 years earlier and acute adrenal insufficiency diagnosed 3 weeks earlier presented with new onset of heart failure New York Heart Association class IV, which had started shortly after initiation of hormone replacement therapy with hydrocortisone 20 mg/day and fludrocortisone 0.3 mg/day. Nine days before admission she had collapsed because of dizziness and had a cerebral concussion and open fracture of her nasal bone, however, no further investigations were carried out at that time. A physical examination revealed leg edema, tachycardia, tachypnea, bilateral basal crepitations, and blood pressure 110/70 mmHg. An electrocardiogram showed sinus tachycardia, low voltage, negative T-waves in V 5 and V 6 and a corrected QT interval of 590 ms. Echocardiography revealed a reduced left ventricular systolic function with an ejection fraction of 30 %, and septal, apical, and anterior wall akinesia. Cardiac magnetic resonance imaging showed relative enhancement of gadolinium, indicating hyperemia and capillary leakage, and no myocardial scars. Because of the improvement in her cardiac function, lack of cardiovascular risk factors, and lack of signs for ischemia on magnetic resonance imaging, no coronary angiography was carried out. The results of sellar and renal magnetic resonance imaging were normal. Her troponin T was slightly elevated. Bisoprolol and ramipril were started. Her fludrocortisone dose was reduced to 0.05 mg/day. Her electrocardiogram and systolic function, documented by echocardiography and magnetic resonance imaging, normalized within 6 months. Although we could not exclude coronary artery disease by coronary angiography, her clinical course and instrumental findings suggest Takotsubo cardiomyopathy of the apical type. Fludrocortisone overdosage and increased myocardial vulnerability due to cortisol deficiency might be pathogenetic factors, whereas myocarditis is unlikely. When hormone replacement in patients with Addison's disease is initiated, cardiac function should be monitored by electrocardiogram and echocardiography.

Learning from regeneration research organisms: The circuitous road to scar free wound healing.

PubMed

Erickson, Jami R; Echeverri, Karen

2018-01-15

The skin is the largest organ in the body and plays multiple essential roles ranging from regulating temperature, preventing infection and ultimately defining who we are physically. It is a highly dynamic organ that constantly replaces the outermost cells throughout life. However, when faced with a major injury, human skin cannot restore a significant lesion to its original functionality, instead a reparative scar is formed. In contrast to this, many other species have the unique ability to regenerate full thickness skin without formation of scar tissue. Here we review recent advances in the field that shed light on how the skin cells in regenerative species react to injury to prevent scar formation versus scar forming humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation.

PubMed

Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

2016-01-01

The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease.

A fast pH-switchable and self-healing supramolecular hydrogel carrier for guided, local catheter injection in the infarcted myocardium.

PubMed

Bastings, Maartje M C; Koudstaal, Stefan; Kieltyka, Roxanne E; Nakano, Yoko; Pape, A C H; Feyen, Dries A M; van Slochteren, Frebus J; Doevendans, Pieter A; Sluijter, Joost P G; Meijer, E W; Chamuleau, Steven A J; Dankers, Patricia Y W

2014-01-01

Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction

PubMed Central

Ma, Yonggang; Mouton, Alan J.; Lindsey, Merry L.

2018-01-01

Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury. In the steady-state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction. In the aging heart, the shift in macrophage phenotype to a proinflammatory subtype leads to inflammaging. Following myocardial infarction (MI), macrophages recruited to the infarct produce both proinflammatory and anti-inflammatory mediators (cytokines, chemokines, matrix metalloproteinases, and growth factors), phagocytize dead cells, and promote angiogenesis and scar formation. These diverse properties are attributed to distinct macrophage subtypes and polarization status. Infarct macrophages exhibit a proinflammatory M1 phenotype early and become polarized toward an anti-inflammatory M2 phenotype later post- MI. Although this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification. This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation. PMID:29106912

Fat Graft, Laser CO₂ and Platelet-Rich-Plasma Synergy in Scars Treatment

PubMed Central

Nita, AC; Orzan, OA; Filipescu, M; Jianu, D

2013-01-01

Abstract Rationale: Many treatments have been proposed for cosmetic or functional improvement of scars. It is known that fat grafts and laser treatment can have beneficial effects on the remodeling of scar tissue, and platelet-rich plasma (PRP) can be effective during the wound-healing process. We hypothesized that laser and PRP can enhance fat graft survival and the combination would be effective in improving scars appearance. Objective: The purpose of this study was to evaluate the efficacy of these combinations in the treatment of atrophic and contractile scars. Methods and Results: From 2008-2013, we treated with this combination 64 patients affected by atrophic and contractile scars involving different body parts. At 6 months the patients’ overall satisfaction rate was excellent for over 50% of the patients. Discussion: The association of an ablative laser CO2 with PRP and autologous fat graft seems to be a promising and effective therapeutic approach for atrophic and contractile scars. Abbreviations: PRP platelet-rich plasma, OTI orotracheal intubation, HLLT high level laser therapy, LLLT low level laser therapy PMID:24868255

Catecholamines and myocardial contractile function during hypodynamia and with an altered thyroid hormone balance

NASA Technical Reports Server (NTRS)

Pruss, G. M.; Kuznetsov, V. I.; Zhilinskaya, A. A.

1980-01-01

The dynamics of catecholamine content and myocardial contractile function during hypodynamia were studied in 109 white rats whose motor activity was severely restricted for up to 30 days. During the first five days myocardial catecholamine content, contractile function, and physical load tolerance decreased. Small doses of thyroidin counteracted this tendency. After 15 days, noradrenalin content and other indices approached normal levels and, after 30 days, were the same as control levels, although cardiac functional reserve was decreased. Thyroidin administration after 15 days had no noticeable effect. A detailed table shows changes in 17 indices of myocardial contractile function during hypodynamia.

Paediatric post-burn scar management in the UK: a national survey.

PubMed

Liuzzi, Francesca; Chadwick, Sarah; Shah, Mamta

2015-03-01

Thermal injuries affect 250,000 people annually in the United Kingdom. As burn survival improves, good scar management is paramount to help individuals living with the resultant scars lead a life without restrictions. Post-burn hypertrophic scars can limit growth in children, interfere with function and cause psychological problems. In the current literature there is great variation in post-burn scar management across the world and in the evidence available for the efficacy of these management modalities. The aim of this study was to investigate the variances if any, in the management of post-burn scarring in children across the UK. A telephone survey of UK paediatric burn services was conducted to obtain information on post-burn scar management and advice given to patients/carers. Of the 19 burn services that participated, all advised moisturising of scars but with variable emphasis on massaging. Silicones and pressure therapy were used by 18 services but commencement of use varied from soon after healing to onset of hypertrophic scarring. Laser therapy, ultrasound therapy and steroid therapy were used sporadically. This study highlights the common modalities of post-burn scar management in children across the UK. However, there is marked variation in timing and selection of the commonly used modalities. Although this study did not investigate the outcomes of scar management, it clearly identifies the need for a well-designed multi-centred study to establish evidence-based best practice in the management of post-burn scarring in children as these modalities are time consuming and not without potential complications. Evidence based practice could potentially lead to significant financial savings to the health service. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Variations in gap junctional intercellular communication and connexin expression in fibroblasts derived from keloid and hypertrophic scars.

PubMed

Lu, Feng; Gao, JianHua; Ogawa, Rei; Hyakusoku, Hiko

2007-03-01

Expression of connexins and other constituent proteins of gap junctions along with gap junctional intercellular communication are involved in cellular development and differentiation processes. In addition, an increasing number of hereditary skin disorders appear to be linked to connexins. Therefore, in this report, the authors studied in vitro gap junctional intercellular communication function and connexin expression in fibroblasts derived from keloid and hypertrophic scar patients. Fibroblasts harvested from each of six keloid and hypertrophic scar patients were used for this study. Gap junctional intercellular communication function was investigated using the gap fluorescence recovery after photobleaching method, and expression of connexin proteins was studied using quantitative confocal microscopic analyses. Compared with normal skin, a decreased level of gap junctional intercellular communication was seen in fibroblasts derived from hypertrophic scar tissue, whereas an extremely low gap junctional intercellular communication level was detected in fibroblasts derived from keloid tissue. We also detected little connexin 43 (Cx43) protein localized in fibroblasts derived from keloids. Moreover, Cx43 protein levels were much lower in fibroblasts derived from hypertrophic scars than in those derived from normal skin. The authors' data suggest that the loss of gap junctional intercellular communication and connexin expression may affect intercellular recognition and thus break the proliferation and apoptosis balance in fibroblasts derived from keloid and hypertrophic scar tissue.

Developmental expression of Drosophila Wiskott-Aldrich Syndrome family proteins

PubMed Central

Rodriguez-Mesa, Evelyn; Abreu-Blanco, Maria Teresa; Rosales-Nieves, Alicia E.; Parkhurst, Susan M.

2012-01-01

Background Wiskott-Aldrich Syndrome (WASP) family proteins participate in many cellular processes involving rearrangements of the actin cytoskeleton. To the date, four WASP subfamily members have been described in Drosophila: Wash, WASp, SCAR, and Whamy. Wash, WASp, and SCAR are essential during early Drosophila development where they function in orchestrating cytoplasmic events including membrane-cytoskeleton interactions. A mutant for Whamy has not yet been reported. Results We generated monoclonal antibodies that are specific to Drosophila Wash, WASp, SCAR, and Whamy, and use these to describe their spatial and temporal localization patterns. Consistent with the importance of WASP family proteins in flies, we find that Wash, WASp, SCAR, and Whamy are dynamically expressed throughout oogenesis and embryogenesis. For example, we find that Wash accumulates at the oocyte cortex. WASp is highly expressed in the PNS, while SCAR is the most abundantly expressed in the CNS. Whamy exhibits an asymmetric subcellular localization that overlaps with mitochondria and is highly expressed in muscle. Conclusion All four WASP family members show specific expression patterns, some of which reflect their previously known roles and others revealing new potential functions. The monoclonal antibodies developed offer valuable new tools to investigate how WASP family proteins regulate actin cytoskeleton dynamics. PMID:22275148

Can the inflammatory response be evaluated using 18F-FDG within zones of microvascular obstruction after myocardial infarction?

PubMed

Prato, Frank S; Butler, John; Sykes, Jane; Keenliside, Lynn; Blackwood, Kimberley J; Thompson, R Terry; White, James A; Mikami, Yoko; Thiessen, Jonathan D; Wisenberg, Gerald

2015-02-01

Inflammation that occurs after acute myocardial infarction plays a pivotal role in healing by facilitating the creation of a supportive scar. (18)F-FDG, which is taken up avidly by macrophages, has been proposed as a marker of cell-based inflammation. However, its reliability as an accurate indicator of inflammation has not been established, particularly in the early postinfarction period when regional myocardial perfusion is often severely compromised. Nine adult dogs underwent left anterior descending coronary occlusion with or without reperfusion. Animals were imaged between 7 and 21 d after infarction with PET/MR imaging after bolus injection of gadolinium-diethylenetriaminepentaacetic acid (DTPA), bolus injection of (18)F-FDG, bolus injection of (99)Tc-DTPA to simulate the distribution of gadolinium-DTPA (which represents its partition coefficient in well-perfused tissue), and injection of (111)In-labeled white blood cells 24 h earlier. After sacrifice, myocardial tissue concentrations of (18)F, (111)In, and (99)Tc were determined in a well counter. Linear regression analysis evaluated the relationships between the concentrations of (111)In and (18)F and the dependence of the ratio of (111)In/(18)F to the apparent distribution volume of (99m)Tc-DTPA. In 7 of 9 animals, (111)In increased as (18)F increased with the other 2 animals, showing weak negative slopes. With respect to the dependence of (111)In/(18)F with partition coefficient, 4 animals showed no dependence and 4 showed a weak positive slope, with 1 animal showing a negative slope. Further, in regions of extensive microvascular obstruction, (18)F significantly underestimated the extent of the presence of (111)In. In the early post-myocardial infarction period, (18)F-FDG PET imaging after a single bolus administration may underestimate the extent and degree of inflammation within regions of microvascular obstruction. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation

PubMed Central

Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

2016-01-01

Purpose: The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. Methods: A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Results: Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Conclusions: Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease. PMID:27648122

The Role of Cardiovascular Magnetic Resonance Imaging in Heart Failure.

PubMed

Peterzan, Mark A; Rider, Oliver J; Anderson, Lisa J

2016-11-01

Cardiovascular imaging is key for the assessment of patients with heart failure. Today, cardiovascular magnetic resonance imaging plays an established role in the assessment of patients with suspected and confirmed heart failure syndromes, in particular identifying aetiology. Its role in informing prognosis and guiding decisions around therapy are evolving. Key strengths include its accuracy; reproducibility; unrestricted field of view; lack of radiation; multiple abilities to characterise myocardial tissue, thrombus and scar; as well as unparalleled assessment of left and right ventricular volumes. T2* has an established role in the assessment and follow-up of iron overload cardiomyopathy and a role for T1 in specific therapies for cardiac amyloid and Anderson-Fabry disease is emerging.

Washout of ⁸²Rb as a marker of impaired tissue integrity, obtained by list-mode cardiac PET/CT: relationship with perfusion/metabolism patterns of myocardial viability.

PubMed

Chien, David T; Bravo, Paco; Higuchi, Takahiro; Merrill, Jennifer; Bengel, Frank M

2011-08-01

Myocardial washout of the potassium analogue (82)Rb may indicate tissue impairment. Few studies have evaluated its usefulness for viability assessment, and controversial results were reported. We revisited this topic using list-mode positron emission tomography (PET)/CT. A total of 22 patients with chronic ischemic cardiomyopathy (ICM) and 11 control subjects with normal CT coronary angiogram were studied. Rest (82)Rb PET/CT studies were acquired in list mode and resampled to static, gated, and dynamic images. Using a 17-segment model, (82)Rb washout was determined by monoexponential fitting of myocardial time-activity curves. In ICM patients, (18)F-fluorodeoxyglucose (FDG) studies were obtained in the same session and segments were classified as normally perfused, mismatch, or matched defect. (82)Rb washout was minimal and homogeneous in control subjects. Normally perfused segments of ICM did not differ (p = 0.33). ICM patients had a left ventricular ejection fraction (LVEF) of 25 ± 12%, 25/353 mismatched, and 46/353 matched defect segments. (82)Rb washout was higher in hypoperfused vs normal segments (p < 0.05), but not different between mismatch and matched defect (p = 0.18). Intraindividual analysis in nine patients showing both FDG mismatch and matched defect confirmed absence of differences. Overall, segmental (82)Rb washout correlated inversely with (82)Rb uptake (r = -0.70; p < 0.05) and less well with FDG uptake (r = -0.31; p < 0.05). Using state-of-the-art PET/CT technology for myocardial viability assessment, (82)Rb washout does not distinguish between perfusion/metabolism patterns of hibernating myocardium and scar. Tissue integrity may be at least partially impaired in hibernation.

Early Cardiac Involvement Affects Left Ventricular Longitudinal Function in Females Carrying α-Galactosidase A Mutation: Role of Hybrid Positron Emission Tomography and Magnetic Resonance Imaging and Speckle-Tracking Echocardiography.

PubMed

Spinelli, Letizia; Imbriaco, Massimo; Nappi, Carmela; Nicolai, Emanuele; Giugliano, Giuseppe; Ponsiglione, Andrea; Diomiaiuti, Tommaso Claudio; Riccio, Eleonora; Duro, Giovanni; Pisani, Antonio; Trimarco, Bruno; Cuocolo, Alberto

2018-04-01

Hybrid 18 F-fluorodeoxyglucose (FDG) positron emission tomography and magnetic resonance imaging may differentiate mature fibrosis or scar from fibrosis associated to active inflammation in patients with Anderson-Fabry disease, even in nonhypertrophic stage. This study was designed to compare the results of positron emission tomography and magnetic resonance cardiac imaging with those of speckle-tracking echocardiography in heterozygous Anderson-Fabry disease females. Twenty-four heterozygous females carrying α-galactosidase A mutation and without left ventricular hypertrophy underwent cardiac positron emission tomography and magnetic resonance using 18 F-FDG for glucose uptake and 2-dimensional strain echocardiography. 18 F-FDG myocardial uptake was quantified by measuring the coefficient of variation (COV) of the standardized uptake value using a 17-segment model. Focal 18 F-FDG uptake with COV >0.17 was detected in 13 patients, including 2 patients with late gadolinium enhancement at magnetic resonance. COV was 0.30±0.14 in patients with focal 18 F-FDG uptake and 0.12±0.03 in those without ( P <0.001). Strain echocardiography revealed worse global longitudinal systolic strain in patients with COV >0.17 compared with those with COV ≤0.17 (-18.5±2.7% versus -22.2±1.8%; P =0.024). For predicting COV >0.17, a global longitudinal strain >-19.8% had 77% sensitivity and 91% specificity and a value >2 dysfunctional segments 92% sensitivity and 100% specificity. In females carrying α-galactosidase A mutation, focal 18 F-FDG uptake represents an early sign of disease-related myocardial damage and is associated with impaired left ventricular longitudinal function. These findings support the hypothesis that inflammation plays an important role in glycosphingolipids storage disorders. © 2018 American Heart Association, Inc.

A Child With a Burn-Related Foot and Ankle Contracture Treated With Multiple Modalities.

PubMed

Yelvington, Miranda; Scoggins, Michelle; White, Leslie

2017-01-01

The presence of hypertrophic scars, which cross lower extremity joints, can often result in decreased range of motion, limitations in functional mobility, and gait deviations. This article reviews a case and describes a multimodal treatment approach. A 6-year-old girl developed aggressive hypertrophic scars following a burn injury. A multimodal treatment approach, including splinting, elastomers, and physical therapy, was developed. Rapid improvements were demonstrated in measured objective outcomes. Early multimodal intervention, in addition to range of motion, stretching, massage, and compression garments, is recommended when treating hypertrophic scars. This case suggests that further study into a multimodal treatment approach may be beneficial to develop a standardized protocol for more efficient scar management.

The experience of scar management for adults with burns: An interpretative phenomenological analysis.

PubMed

Martin, C; Bonas, S; Shepherd, L; Hedges, E

2016-09-01

Burns can have both physical and psychological effects on individuals. Pressure garments and silicone gels are used to improve the aesthetic appearance and functions of the skin, but these treatments have been associated with various physical, emotional, sexual and social difficulties. Interpretative phenomenological analysis (IPA) was used to explore participants' experiences of scar management. IPA examines individual experiences before comparing results across cases, and is suited to capture the different ways in which individuals experience a phenomena as well as cautiously looking at patterns across cases. Eight burn patients who had experienced scar management, including pressure garments, were interviewed. Two superordinate themes were identified: Assimilation of Pressure Garment Identity, and Psychosocial Functions of the Pressure Garments. The findings offered insight into the positive and negative experiences of scar management, describing the diverse personal and social functions of the pressure garments and how they became integrated into participants' identities. By understanding the individual nature of these experiences, healthcare professionals can enhance support around these issues and potentially aid adherence to treatment. Further research with different demographic groups as well as for other burn treatments would be useful to develop and contextualise these findings. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Epicardial infarct repair with bioinductive extracellular matrix promotes vasculogenesis and myocardial recovery.

PubMed

Mewhort, Holly E M; Turnbull, Jeannine D; Satriano, Alessandro; Chow, Kelvin; Flewitt, Jacqueline A; Andrei, Adin-Cristian; Guzzardi, David G; Svystonyuk, Daniyil A; White, James A; Fedak, Paul W M

2016-05-01

Infarcted myocardium can remodel after successful reperfusion, resulting in left ventricular dilation and heart failure. Epicardial infarct repair (EIR) using a bioinductive extracellular matrix (ECM) biomaterial is a novel surgical approach to promote endogenous myocardial repair and functional recovery after myocardial infarction. Using a pre-clinical porcine model of coronary ischemia-reperfusion, we assessed the effects of EIR on regional functional recovery, safety, and possible mechanisms of benefit. An ECM biomaterial (CorMatrix ECM) was applied to the epicardium after 75 minutes of coronary ischemia in a porcine model. Following ischemia-reperfusion injury, animals were randomly assigned in 2:1 fashion to EIR (n = 8) or sham treatment (n = 4). Serial cardiac magnetic resonance imaging was performed on normal (n = 4) and study animals at baseline (1 week) and 6 weeks after treatment. Myocardial function and tissue characteristics were assessed. Functional myocardial recovery was significantly increased by EIR compared with sham treatment (change in regional myocardial contraction at 6 weeks, 28.6 ± 14.0% vs 4.2 ± 13.5% wall thickening, p < 0.05). Animals receiving EIR had reduced adhesions compared with animals receiving sham treatment (1.44 ± 0.51 vs 3.08 ± 0.89, p < 0.05). Myocardial fibrosis was not increased, and EIR did not cause myocardial constriction, as left ventricular compliance by passive pressure distention at matched volumes was similar between groups (13.9 ± 4.0 mm Hg in EIR group vs 16.0 ± 5.2 mm Hg in sham group, p = 0.61). Animals receiving EIR showed evidence of vasculogenesis in the region of functional recovery. In addition to the beneficial effects of successful reperfusion, EIR using a bioinductive ECM enhances myocardial repair and functional recovery. Clinical translation of EIR early after myocardial infarction as an adjunct to surgical revascularization may be warranted in the future. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Management of vocal fold scar with autologous fat implantation: perceptual results.

PubMed

Neuenschwander, M C; Sataloff, R T; Abaza, M M; Hawkshaw, M J; Reiter, D; Spiegel, J R

2001-06-01

Vocal fold scar disrupts the mucosal wave and interferes with glottic closure. Treatment involves a multidisciplinary approach that includes voice therapy, medical management, and sometimes surgery. We reviewed the records of the first eight patients who underwent autologous fat implantation for vocal fold scar. Information on the etiology of scar, physical findings, and prior interventions were collected. Videotapes of videostroboscopic findings and perceptual voice ratings [Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS)] were randomized and analyzed independently by four blinded observers. Etiology of scar included mass excision (7), vocal fold stripping (3), congenital sulcus (2), and hemorrhage (1). Prior surgical procedures performed included thyroplasty (1), autologous fat injection (9), excision of scar (2), and lysis of adhesions (2). Strobovideolaryngoscopy: Statistically significant improvement was found in glottic closure, mucosal wave, and stiffness (P = 0.05). Perceptual ratings (GRBAS): Statistically significant improvement was found in all five parameters, including overall Grade, Roughness, Breathiness, Asthenia, and Strain (P = 0.05). Patients appear to have improved vocal fold function and quality of voice after autologous fat implantation in the vocal fold. Autologous fat implantation is an important adjunctive procedure in the management of vocal fold scar, and a useful addition to the armamentarium of the experienced phonomicrosurgeon.

Mesenchymal stem cell therapy for attenuation of scar formation during wound healing.

PubMed

Jackson, Wesley M; Nesti, Leon J; Tuan, Rocky S

2012-05-31

Scars are a consequence of cutaneous wound healing that can be both unsightly and detrimental to the function of the tissue. Scar tissue is generated by excessive deposition of extracellular matrix tissue by wound healing fibroblasts and myofibroblasts, and although it is inferior to the uninjured skin, it is able to restore integrity to the boundary between the body and its environment. Scarring is not a necessary process to repair the dermal tissues. Rather, scar tissue forms due to specific mechanisms that occur during the adult wound healing process and are modulated primarily by the inflammatory response at the site of injury. Adult tissue-derived mesenchymal stem cells, which participate in normal wound healing, are trophic mediators of tissue repair. These cells participate in attenuating inflammation in the wound and reprogramming the resident immune and wound healing cells to favor tissue regeneration and inhibit fibrotic tissue formation. As a result, these cells have been considered and tested as a likely candidate for a cellular therapy to promote scar-less wound healing. This review identifies specific mechanisms by which mesenchymal stem cells can limit tissue fibrosis and summarizes recent in vivo studies where these cells have been used successfully to limit scar formation.

Detection and monitoring of cardiotoxicity-what does modern cardiology offer?

PubMed

Jurcut, Ruxandra; Wildiers, Hans; Ganame, Javier; D'hooge, Jan; Paridaens, Robert; Voigt, Jens-Uwe

2008-05-01

With new anticancer therapies, many patients can have a long life expectancy. Treatment-related comorbidities become an issue for cancer survivors. Cardiac toxicity remains an important side effect of anticancer therapies. Myocardial dysfunction can become apparent early or long after end of therapy and may be irreversible. Detection of cardiac injury is crucial since it may facilitate early therapeutic measures. Traditionally, chemotherapy-induced cardiotoxicity has been detected by measuring changes in left ventricular ejection fraction. This parameter is, however, insensitive to subtle changes in myocardial function as they occur in early cardiotoxicity. This review will discuss conventional and modern cardiologic approaches of assessing myocardial function. It will focus on Doppler myocardial imaging, a method which allows to sensitively measure myocardial function parameters like myocardial velocity, deformation (strain), or deformation rate (strain rate) and which has been shown to reliably detect early abnormalities in both regional and global myocardial function in an early stage. Other newer echocardiographic function estimators are based on automated border detection algorithms and ultrasonic integrated backscatter analysis. A further technique to be discussed is dobutamine stress echocardiography. The use of new biomarkers like B-type natriuretic peptide and troponin and less often used imaging techniques like magnetic resonance imaging and computed tomography will also be mentioned.

[Influence of WeChat platform on the compliance of continuous treatment of scar in adult burn patients].

PubMed

Wang, F; Zhang, H L

2018-03-20

Objective: To explore influence of the WeChat platform on the compliance of continuous treatment of scar in adult burn patients. Methods: A total of 124 adult burn patients, conforming to the study criteria, admitted in the Department of Burns of our hospital from January 2015 to January 2016 were divided into WeChat group ( n =63) and control group ( n =61) according to the random number table. Patients in control group only received regular discharging rehabilitation guide, while patients in WeChat group received regular discharging rehabilitation guide and joined WeChat platform after being discharged from hospital. Through pushing rehabilitation plan and rehabilitation related knowledge, organizing support discussion of burn patients, answering the patients' questions, members of WeChat platform intervention group conducted continuous treatment for 6 months on patients of WeChat group. The compliance of functional exercise of patients in two groups in one week before discharge and 3 and 6 months after discharge was evaluated by using the self-made functional exercise compliance log sheet. The compliance of using anti-scar drug and appliance of patients in two groups in 3 and 6 months after discharge was evaluated by using self-made anti-scar drug and appliance usage log sheets. Data were processed with chi-square test, independent sample t test, non-parametric rank sum test of independent sample, and Wilcoxon rank sum test. Results: (1) The compliance ratio of functional exercise of patients in WeChat group (95.24%, 60/63) was close to 93.44% (57/61) in control group in one week before discharge ( χ (2)=0.188, P >0.05). The compliance ratios of functional exercise of patients in WeChat group were respectively 93.65% (59/63) and 87.30% (55/63) in 3 and 6 months after discharge, which were higher than 68.85% (42/61) and 65.57% (40/61) in control group ( χ (2)=12.615, 8.166, P <0.01). (2) The compliance of using anti-scar drug of patients in WeChat group was significantly better than that in control group in 3 and 6 months after discharge ( Z =-4.150, -4.563, P <0.01). (3) The compliance of using anti-scar appliance of patients in WeChat group in 3 and 6 months after discharge was obviously better than that in control group ( Z =-4.242, -4.301, P <0.01). Conclusions: By using WeChat platform to provide guide for scar rehabilitation continuous treatment, adult burn patients have better compliance to functional exercise and usage of anti-scar drug and appliance.

Accuracy of remote burn scar evaluation via live video-conferencing technology.

PubMed

Cai, Lawrence Z; Caceres, Maria; Dangol, Mohan Krishna; Nakarmi, Kiran; Rai, Shankar Man; Chang, James; Gibran, Nicole S; Pham, Tam N

2016-12-05

Telemedicine in outpatient burn care, particularly in burn scar management, may provide cost-effective care and comes highly rated by patients. However, an effective scar scale using both video and photographic elements has not been validated. The purpose of this study is to test the reliability of the Patient and Observer Scar Assessment Scale (POSAS) using live video-conferencing. A prospective study was conducted with individuals with healed burn scars in Kathmandu, Nepal. Three independent observers assessed 85 burn scars from 17 subjects, using the Observer portion to evaluate vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion. The on-site observer was physically present with the subjects and used a live videoconferencing application to show the scars to two remote observers in the United States. Subjects used the Patient portion to evaluate the scar that they believed appeared the worst appearance and had the greatest impact on function. The single-rater reliability of the Observer scale was acceptable (ICC>0.70) in overall opinion, thickness, pliability, and surface area. The average-rater reliability for three observers was acceptable (ICC>0.70) for all parameters except for vascularity. When comparing Patients' and Observers' overall opinion scores, patients consistently reported worse opinion. Evaluation of burn scars using the Patient and Observer Scar Assessment Scale can be accurately performed via live videoconferencing and presents an opportunity to expand access to burn care to rural communities, particularly in low- and middle-income countries, where patients face significant access barriers to appropriate follow-up care. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

A novel spectral imaging system for quantitative analysis of hypertrophic scar

NASA Astrophysics Data System (ADS)

Ghassemi, Pejhman; Shupp, Jeffrey W.; Moffatt, Lauren T.; Ramella-Roman, Jessica C.

2013-03-01

Scarring can lead to significant cosmetic, psychosocial, and functional consequences in patients with hypertrophic scars from burn and trauma injuries. Therefore, quantitative assessment of scar is needed in clinical diagnosis and treatment. The Vancouver Scar Scale (VSS), the accepted clinical scar assessment tool, was introduced in the nineties and relies only on the physician subjective evaluation of skin pliability, height, vascularity, and pigmentation. To date, no entirely objective method has been available for scar assessment. So, there is a continued need for better techniques to monitor patients with scars. We introduce a new spectral imaging system combining out-of-plane Stokes polarimetry, Spatial Frequency Domain Imaging (SFDI), and three-dimensional (3D) reconstruction. The main idea behind this system is to estimate hemoglobin and melanin contents of scar using SFDI technique, roughness and directional anisotropy features with Stokes polarimetry, and height and general shape with 3D reconstruction. Our proposed tool has several advantages compared to current methodologies. First and foremost, it is non-contact and non-invasive and thus can be used at any stage in wound healing without causing harm to the patient. Secondarily, the height, pigmentation, and hemoglobin assessments are co-registered and are based on imaging and not point measurement, allowing for more meaningful interpretation of the data. Finally, the algorithms used in the data analysis are physics based which will be very beneficial in the standardization of the technique. A swine model has also been developed for hypertrophic scarring and an ongoing pre-clinical evaluation of the technique is being conducted.

Hypertrophic scarring: the greatest unmet challenge following burn injury

PubMed Central

Finnerty, Celeste C; Jeschke, Marc G; Branski, Ludwik K; Barret, Juan P.; Dziewulski, Peter; Herndon, David N

2017-01-01

Summary Improvements in acute burn care have enabled patients to survive massive burns which would have once been fatal. Now up to 70% of patients develop hypertrophic scars following burns. The functional and psychosocial sequelae remain a major rehabilitative challenge, decreasing quality of life and delaying reintegration into society. The current approach is to optimise the healing potential of the burn wound using targeted wound care and surgery in order to minimise the development of hypertrophic scarring. This approach often fails, and modulation of established scar is continued although the optimal indication, timing, and combination of therapies have yet to be established. The need for novel treatments is paramount, and future efforts to improve outcomes and quality of life should include optimisation of wound healing to attenuate or prevent hypertrophic scarring, well-designed trials to confirm treatment efficacy, and further elucidation of molecular mechanisms to allow development of new preventative and therapeutic strategies. PMID:27707499

Bacterial factors in the formation of renal scars. An experimental study on the role of Escherichia coli P-fimbriation and hydrophobicity.

PubMed

Arnold, A J; Sunderland, D; Rickwood, A M; Hart, C A

1993-11-01

A model capable of comparing the effects of bacterial virulence factors on renal scarring in vivo has been developed using the female piglet. By creating, at open surgery, unilateral vesicoureteric reflux (VUR) and quantifying scarring both by uptake of an isotope bound to functioning renal parenchyma and by planimetry of the surface area scarred, the effects of 2 organisms, a P-fimbriate Escherichia coli and an E. coli K1 have been compared. The P-fimbriate E. coli was shown to express P-fimbriae in freshly voided urine, was more hydrophobic and produced smaller scars. This indicates that neither the hydrophobicity nor P-fimbriation of the organism causing urinary tract infection (UTI) is of prime importance for the development of renal scars and is evidence against the "big bang" theory for the development of renal scars. Studies on the association of UTI with VUR showed that infection with both E. coli under study led to VUR on the side contralateral to the side undergoing surgery. It seems likely that a non-specific effect of UTI, such as bladder oedema, is responsible for this acquired VUR. An effect of the 2 bacteria under study on the lower urinary tract was observed in that infection with the P-fimbriate E. coli allowed the retention of an intravesical wax plug, whereas infection with E. coli K1 did not. Epidemiological data have shown that the majority of upper urinary tract infections in children are associated with UTI by P-fimbriate organisms. Such an association may be explained in part by an effect of P-fimbriate bacteria on lower urinary tract function rather than an effect on the upper urinary tract.

Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury.

PubMed

Zhang, Shu-xin; Huang, Fengfa; Gates, Mary; White, Jason; Holmberg, Eric G

2010-08-30

Intrathecal infusion has been widely used to directly deliver drugs or neurotrophins to a lesion site following spinal cord injury. Evidence shows that intrathecal infusion is efficient for 7 days but is markedly reduced after 14 days, due to time dependent occlusion. In addition, extensive fibrotic scarring is commonly observed with intrathecal infusion. These anomalies need to be clearly elucidated in histology. In the present study, all adult Long-Evans rats received a 25 mm contusion injury on spinal cord T10 produced using the NYU impactor device. Immediately after injury, catheter tubing with an outer diameter of 0.38 mm was inserted through a small dural opening at L3 into the subdural space with the tubing tip positioned near the injury site. The tubing was connected to an Alzet mini pump, which was filled with saline solution and was placed subcutaneously. Injured rats without tubing served as control. Rats were behaviorally tested for 6 weeks using the BBB locomotor rating scale and histologically assessed for tissue scarring. Six weeks later, we found that the intrathecal tubing caused extensive scarring and inflammation, related to neutrophils, macrophages and plasma cells. The tubing's tip was occluded by scar tissue and inflammatory cells. The scar tissue surrounding the tubing consists of 20-70 layers of fibroblasts and densely compacted collagen fibers, seriously compressing and damaging the cord tissue. BBB scores of rats with intrathecal tubing were significantly lower than control rats (p<0.01) from 2 weeks after injury, implying serious impairment of functional recovery caused by the scarring. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Current Therapeutic Approach to Hypertrophic Scars

PubMed Central

Mokos, Zrinka Bukvić; Jović, Anamaria; Grgurević, Lovorka; Dumić-Čule, Ivo; Kostović, Krešimir; Čeović, Romana; Marinović, Branka

2017-01-01

Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome. PMID:28676850

Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1

PubMed Central

Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong

2016-01-01

Background: Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. Methods: The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Results: Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (CcO), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 (P<0.05). Conclusion: The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression. PMID:27830025

Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1.

PubMed

Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong

2016-01-01

Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (C c O), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 ( P <0.05). The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression.

Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.

PubMed

Eirin, Alfonso; Zhu, Xiang-Yang; Ferguson, Christopher M; Riester, Scott M; van Wijnen, Andre J; Lerman, Amir; Lerman, Lilach O

2015-01-19

Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated. PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis. Intra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.

Modulation of Wound Healing and Scar Formation by MG53 Protein-mediated Cell Membrane Repair*

PubMed Central

Li, Haichang; Duann, Pu; Lin, Pei-Hui; Zhao, Li; Fan, Zhaobo; Tan, Tao; Zhou, Xinyu; Sun, Mingzhai; Fu, Minghuan; Orange, Matthew; Sermersheim, Matthew; Ma, Hanley; He, Duofen; Steinberg, Steven M.; Higgins, Robert; Zhu, Hua; John, Elizabeth; Zeng, Chunyu; Guan, Jianjun; Ma, Jianjie

2015-01-01

Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53−/− mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing. PMID:26306047

Prognostic value of stress myocardial perfusion positron emission tomography: results from a multicenter observational registry.

PubMed

Dorbala, Sharmila; Di Carli, Marcelo F; Beanlands, Rob S; Merhige, Michael E; Williams, Brent A; Veledar, Emir; Chow, Benjamin J W; Min, James K; Pencina, Michael J; Berman, Daniel S; Shaw, Leslee J

2013-01-15

The primary objective of this multicenter registry was to study the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) and the improved classification of risk in a large cohort of patients with suspected or known coronary artery disease (CAD). Limited prognostic data are available for MPI with PET. A total of 7,061 patients from 4 centers underwent a clinically indicated rest/stress rubidium-82 PET MPI, with a median follow-up of 2.2 years. The primary outcome of this study was cardiac death (n = 169), and the secondary outcome was all-cause death (n = 570). Net reclassification improvement (NRI) and integrated discrimination analyses were performed. Risk-adjusted hazard of cardiac death increased with each 10% myocardium abnormal with mildly, moderately, or severely abnormal stress PET (hazard ratio [HR]: 2.3 [95% CI: 1.4 to 3.8; p = 0.001], HR: 4.2 [95% CI: 2.3 to 7.5; p < 0.001], and HR: 4.9 [95% CI: 2.5 to 9.6; p < 0.0001], respectively [normal MPI: referent]). Addition of percent myocardium ischemic and percent myocardium scarred to clinical information (age, female sex, body mass index, history of hypertension, diabetes, dyslipidemia, smoking, angina, beta-blocker use, prior revascularization, and resting heart rate) improved the model performance (C-statistic 0.805 [95% CI: 0.772 to 0.838] to 0.839 [95% CI: 0.809 to 0.869]) and risk reclassification for cardiac death (NRI 0.116 [95% CI: 0.021 to 0.210]), with smaller improvements in risk assessment for all-cause death. In patients with known or suspected CAD, the extent and severity of ischemia and scar on PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Inhibition of quantum transport due to 'scars' of unstable periodic orbits

NASA Technical Reports Server (NTRS)

Jensen, R. V.; Sanders, M. M.; Saraceno, M.; Sundaram, B.

1989-01-01

A new quantum mechanism for the suppression of chaotic ionization of highly excited hydrogen atoms explains the appearance of anomalously stable states in the microwave ionization experiments of Koch et al. A novel phase-space representation of the perturbed wave functions reveals that the inhibition of quantum transport is due to the selective excitation of wave functions that are highly localized near unstable periodic orbits in the chaotic classical phase space. The 'scarred' wave functions provide a new basis for the quantum description of a variety of classically chaotic systems.

Critical assessment of the anterolateral thigh flap donor site.

PubMed

Townley, W A; Royston, E C; Karmiris, N; Crick, A; Dunn, R L R

2011-12-01

The free anterolateral thigh flap (ALT) is now used as a 'workhorse flap'. The donor site morbidity is thought to be minimal, although most evidence derives from questionnaire-based studies rather than rigorous objective clinical assessment. In particular, robust quantitative data on thigh sensibility and quadriceps function is lacking. The aim of this study was to provide a comprehensive clinical assessment of donor site morbidity. We performed a prospective study of consecutive free ALT perforator flaps performed at Salisbury Foundation Trust between March 2008 and April 2010. The donor site was assessed at six months including a questionnaire (symptoms, function), scar analysis (Vancouver Scar Scale, VSS), and evaluation of quadriceps power and lateral thigh sensibility (compared with the contralateral unoperated thigh). One hundred ALT flaps were performed on 97 patients (mean age 46.8 years). The donor site was closed directly in 88 cases and using a split skin graft in 12 cases. At follow-up (n=68), tingling was the most common reported symptom (59%), whereas pain, itching and muscle herniation were reported infrequently. Donor site scars were mostly flat, pale and soft but widened. Pathological scarring was rare. Sensibility was reduced in donor thighs (p<0.001) and correlated with flap width but peak quadriceps contraction was similar between donor and unoperated thighs. There was a high throughput and diverse application of ALT flap reconstructions during the study period. Reduced sensibility was common around the scar but rarely troublesome. Quadriceps function was not affected even when dissection of intramuscular perforators was required. The ALT is a versatile flap that can deliver a large skin paddle with minimal impact on thigh function. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures

PubMed Central

Trieschmann, Jan; Bettin, Daniel; Haustein, Moritz; Köster, Annette; Molcanyi, Marek; Halbach, Marcel; Hanna, Mira; Fouad, Mariam; Brockmeier, Konrad; Hescheler, Jürgen; Pfannkuche, Kurt; Hannes, Tobias

2016-01-01

Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5 ± 15.2% versus 9.3 ± 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V max) were reduced (amplitude: 52.3 ± 1.7 mV versus 65.1 ± 1.5 mV, V max: 7.0 ± 1.0 V/s versus 36.5 ± 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 ± 1.0 ms versus 16.8 ± 1.9 ms, p < 0.001; APD90: 52.2 ± 1.5 ms versus 43.3 ± 3.3 ms, p < 0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology. PMID:26880949

The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures.

PubMed

Trieschmann, Jan; Bettin, Daniel; Haustein, Moritz; Köster, Annette; Molcanyi, Marek; Halbach, Marcel; Hanna, Mira; Fouad, Mariam; Brockmeier, Konrad; Hescheler, Jürgen; Pfannkuche, Kurt; Hannes, Tobias

2016-01-01

Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5 ± 15.2% versus 9.3 ± 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V max) were reduced (amplitude: 52.3 ± 1.7 mV versus 65.1 ± 1.5 mV, V max: 7.0 ± 1.0 V/s versus 36.5 ± 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 ± 1.0 ms versus 16.8 ± 1.9 ms, p < 0.001; APD90: 52.2 ± 1.5 ms versus 43.3 ± 3.3 ms, p < 0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology.

Biological properties of human skeletal myoblasts genetically modified to simultaneously overexpress the pro-angiogenic factors vascular endothelial growth factor-A and fibroblast growth factor-4.

PubMed

Zimna, A; Janeczek, A; Rozwadowska, N; Fraczek, M; Kucharzewska, P; Rucinski, M; Mietkiewski, T; Kurpisz, M

2014-04-01

Myocardial infarction results in cardiomyocyte loss and may eventually lead to cardiac failure. Skeletal myoblast transplantation into the scar area may compensate for this observed cell loss by strengthening the weakened myocardium and inducing myogenesis. Moreover, skeletal myoblasts may serve as potential transgene carriers for the myocardium (i.e., delivering pro-angiogenic factors, which may potentially improve blood perfusion in infarcted heart). We examined the influence of the simultaneous overexpression of two potent pro-angiogenic factors, fibroblast growth factor-4 (FGF-4) and vascular endothelial growth factor (VEGF), on human primary myoblast proliferation, cell cycle, resistance to hypoxic stress conditions and myogenic gene expression, as well as the induction of pro-angiogenic activities. We used a bicistronic plasmid vector encoding two factors introduced via an efficient myoblast electroporation method. The levels of overexpressed proteins were assessed, and their functionality at capillary formation was evaluated. This combined approach led to a high level of non-viral transient overexpression of both pro-angiogenic proteins, which proved to be potent regulators of blood vessel development assayed in capillary formation tests. We demonstrated in in vitro conditions that the transfection of human skeletal myoblasts with both FGF-4 and VEGF did not affect their basic biological properties such as the cell cycle, proliferation or expression of myogenic lineage-specific genes, and the modified cells adapted to oxidative stress conditions. Overall, the results obtained suggest that the applied combined approach with the use of two pro-angiogenic genes overexpressed in skeletal muscle stem cells may be an interesting alternative for the effective therapy of myocardial infarction in animal models and/or prospective clinical trials.

S-Nitrosoglutathione Reductase Deficiency Enhances the Proliferative Expansion of Adult Heart Progenitors and Myocytes Post Myocardial Infarction

PubMed Central

Hatzistergos, Konstantinos E; Paulino, Ellena C; Dulce, Raul A; Takeuchi, Lauro M; Bellio, Michael A; Kulandavelu, Shathiyah; Cao, Yenong; Balkan, Wayne; Kanashiro-Takeuchi, Rosemeire M; Hare, Joshua M

2015-01-01

Background Mammalian heart regenerative activity is lost before adulthood but increases after cardiac injury. Cardiac repair mechanisms, which involve both endogenous cardiac stem cells (CSCs) and cardiomyocyte cell-cycle reentry, are inadequate to achieve full recovery after myocardial infarction (MI). Mice deficient in S-nitrosoglutathione reductase (GSNOR−⁄−), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI. Here, we tested the hypothesis that GSNOR activity modulates cardiac cell proliferation in the post-MI adult heart. Methods and Results GSNOR−⁄− and C57Bl6/J (wild-type [WT]) mice were subjected to sham operation (n=3 GSNOR−⁄−; n=3 WT) or MI (n=41 GSNOR−⁄−; n=65 WT). Compared with WT,GSNOR−⁄− mice exhibited improved survival, cardiac performance, and architecture after MI, as demonstrated by higher ejection fraction (P<0.05), lower endocardial volumes (P<0.001), and diminished scar size (P<0.05). In addition, cardiomyocytes from post-MI GSNOR−⁄− hearts exhibited faster calcium decay and sarcomeric relaxation times (P<0.001). Immunophenotypic analysis illustrated that post-MI GSNOR−⁄− hearts demonstrated enhanced neovascularization (P<0.001), c-kit+ CSC abundance (P=0.013), and a ≈3-fold increase in proliferation of adult cardiomyocytes and c-kit+/CD45− CSCs (P<0.0001 and P=0.023, respectively) as measured by using 5-bromodeoxyuridine. Conclusions Loss of GSNOR confers enhanced post-MI cardiac regenerative activity, characterized by enhanced turnover of cardiomyocytes and CSCs. Endogenous denitrosylases exert an inhibitory effect over cardiac repair mechanisms and therefore represents a potential novel therapeutic target. PMID:26178404

LV mechanical dispersion as a predictor of ventricular arrhythmia in patients with advanced systolic heart failure : A pilot study.

PubMed

Banasik, G; Segiet, O; Elwart, M; Szulik, M; Lenarczyk, R; Kalarus, Z; Kukulski, T

2016-11-01

Myocardial mechanical dyssynchrony induced by the presence of postinfarction scar and/or conduction abnormalities in patients with a left ventricular ejection fraction (LVEF) of < 35 % may be associated with a greater propensity toward inducing serious ventricular arrhythmia [(ventricular tachycardia (VT), ventricular fibrillation (VF)] and sudden cardiac death. The assessment of regional myocardial function using tissue Doppler echocardiography (TDE) allows for noninvasive analysis of regional mechanical dysfunction (LV mechanical dispersion). The aim of this study was to evaluate the TDE-based mechanical dispersion as a potential echocardiographic predictor of VT/VF. The study group consisted of 47 consecutive ambulatory patients with implanted cardiac resynchronization therapy-defibrillator (CRT-D) devices who were divided into two groups: Group 1 (n = 29) comprised patients with recorded episodes of VT/VF, in whom baseline TDE data were available, and group 2 (n = 18) comprised patients without registered VT/VF in the device memory within 4 years after implantation. LV mechanical dispersion was defined as the standard deviation of the time measured from the beginning of the QRS complex to the peak longitudinal strain in apical four-chamber and two-chamber views. A retrospective quantitative assessment of LV regional deformation was based on the color tissue velocity recordings. The average time to event after implantation was 345 days. Patients with electrical events demonstrated greater mechanical dispersion: 99.14 ± 33.60 vs. 72.98 ± 19.70, p=0.002. During the 4-year follow-up, patients with documented VT/VF were characterized by significantly higher LV mechanical dispersion as compared with patients without electrical events. Measurement of LV mechanical dispersion might be helpful in determining the risk of sudden cardiac death.

Augmented healing process in female mice with acute myocardial infarction.

PubMed

Wang, Fangfei; Keimig, Thomas; He, Quan; Ding, Jennifer; Zhang, Zhenggang; Pourabdollah-Nejad, Siamak; Yang, Xiao-Ping

2007-09-01

It is well established that premenopausal women are protected from cardiovascular disease. This gender difference in favor of females is also demonstrated in animal studies. Our research group previously found that female mice had much lower incidence of cardiac rupture and mortality than did males during the acute phase of myocardial infarction (MI); however, the mechanisms responsible for such protection are not fully understood. The aim of this study was to determine whether the favorable cardiac effect observed in female mice with MI is due to an augmented healing process that includes less inflammation, reduced matrix degradation, and enhanced neovascularization. Twelve-week-old male and female C57BL/6J mice were subjected to MI by ligating the left anterior descending coronary artery and then euthanized at 1, 4, 7, or 14 days post-MI. Inflammatory cell infiltration and myofibroblast transformation, matrix metalloproteinase (MMP)-2 and MMP-9 activity, tissue inhibitor of metalloproteinase (TIMP)-I expression, and neovascularization were examined by immunohistochemistry, zymography, Western blot, and laser scanning confocal microscopy, respectively. Cardiac function was evaluated by echocardiography on day 14. We found that: (1) neutrophil infiltration during the early phase of MI (1-4 days) was much lower in females than in males and was associated with lower MMP-9 activity and higher TIMP-1 protein expression, indicating less-exaggerated inflammation and extracellular matrix degradation in females; (2) myofibroblast transformation, as indicated by expression of alpha-smooth muscle actin, was significantly greater in females than in males at day 7 of MI (P<0.05), indicating facilitated collagen deposition and scar formation; and (3) neovascularization (vascular area in the infarct border) was markedly increased in females, and was associated with better preserved cardiac function and less left ventricular dilatation. Our data suggest that less-exaggerated early inflammation and augmented reparative fibrotic response, indicated by enhanced myofibroblast transformation, may contribute greatly to low rupture rates in females during the acute and subacute phases of MI, whereas enhanced neovascularization may lead to better preserved cardiac function post-MI.

[Burn scars: rehabilitation and skin care].

PubMed

Rochet, Jean-Michel; Zaoui, Affif

2002-12-15

Burn rehabilitation main goal is to minimize the consequences of hypertrophic scars and concomitant contractures. The treatment principles rely on the association of joint posture, continuous pressure completed with range of motion to prevent joint fusion (which happens to adults but not to children). Throughout the different treatment phases and wound evolution, reassessment is necessary to review rehabilitation goals and activities. During the acute phase the alternance of positioning is prioritized in order to keep the affected extremities in antideformity position using splint or other devices. At the rehabilitation phase, treatment is focussed on active/passive range of motion (skin posture) strengthening exercises and use of dynamic splint is introduced to correct contractures. After their discharge home, patients benefit from outpatient rehab until scar maturation (approximately 18 months). The treatment consists mainly on active/passive range of motion, scar massage, strengthening exercise and endurance retraining. Also modalities (such as thermal bath and high pressure water spray) are used to address itching problems and for scar softening. Finally, reconstructive surgery can be performed to correct excessive scarring or joint contracture for better functional or cosmetic outcome.

Common threads in cardiac fibrosis, infarct scar formation, and wound healing.

PubMed

Czubryt, Michael P

2012-11-01

Wound healing, cardiac fibrosis, and infarct scar development, while possessing distinct features, share a number of key functional similarities, including extracellular matrix synthesis and remodeling by fibroblasts and myofibroblasts. Understanding the underlying mechanisms that are common to these processes may suggest novel therapeutic approaches for pathologic situations such as fibrosis, or defective wound healing such as hypertrophic scarring or keloid formation. This manuscript will briefly review the major steps of wound healing, and will contrast this process with how cardiac infarct scar formation or interstitial fibrosis occurs. The feasibility of targeting common pro-fibrotic growth factor signaling pathways will be discussed. Finally, the potential exploitation of novel regulators of wound healing and fibrosis (ski and scleraxis), will be examined.

The Na+/H+ exchange inhibitor cariporide is washed out of the myocardium by crystalloid cardioplegia.

PubMed

Bechtel, J F M; Eichler, W; Toerber, K; Weidtmann, B; Hernandez, M; Klotz, K F; Sievers, H H; Bartels, C

2006-08-01

Inhibition of the Na (+)/H (+) exchanger (NHE) is cardioprotective, but dosage and timing of NHE-inhibitors are critical for their efficacy. We studied the effect of a new dosing regime of the NHE-inhibitor cariporide on myocardial function and damage after cardioplegic arrest (CPA) and determined its myocardial and serum concentrations. 3 pigs received a bolus of 180 mg cariporide intravenously (i. v.) and were sacrificed shortly thereafter to allow measurement of the myocardial concentrations of cariporide. Subsequently, 10 pigs were randomized to receive either i. v. cariporide (bolus followed by an infusion of 40 mg/h) or placebo. Cardiopulmonary bypass was initiated, and the heart was arrested for 60 minutes by infusion of St. Thomas Hospital solution. Left ventricular (LV) function was studied using microsonometry. Myocardial damage was assessed by troponin T. Serum concentrations of cariporide were measured throughout the study, and myocardial concentrations were measured before the end of CPA and 180 minutes thereafter. Cariporide was present in all myocardial specimens (median: 1.4 ng/mg) studied previously. In the main study, LV function or myocardial damage did not differ significantly between the groups at any time point. Stable serum cariporide concentrations were achieved (3.4 +/- 0.5 microg/ml). Cariporide was detectable in only one of the myocardial biopsies obtained before the end of CPA, but 180 minutes thereafter, the myocardial cariporide concentration was 2.5 +/- 0.3 ng/mg. We observed no effect of i. v. cariporide on LV function or myocardial damage after cardioplegic arrest. Our data suggest that cariporide is washed out of the myocardium by repeated application of crystalloid cardioplegia. Thus, the mode of delivery also appears to be critical for cardioprotection with NHE-inhibitors.

[Assessment of myocardial perfusion and left ventricular function with 99mTc-PPN 1011].

PubMed

Kumita, S; Mizumura, S; Oishi, T; Kumazaki, T; Sano, J; Yamazaki, Y; Munakata, K

1993-04-01

First-pass radionuclide angiography (FPRNA) was performed with the new myocardial perfusion agent 99mTc-1,2,bis[bis(2-ethoxyethyl)phosphino] ethane (99mTc-PPN 1011) on stress and at rest. One hour after that, myocardial perfusion was counted by 99mTc-PPN 1011 SPECT. Left ventricular ejection fraction (LVEF) obtained by FPRNA correlated with that by multigated image with 99mTc-HSAD (r = 0.94, n = 11). The reduction of left ventricular function under the exercise (delta LVEF) and the increase of severity score (delta Severity score) have a good relation (r = 0.88) in 7 patients with prior myocardial infarction. Thus 99mTc-PPN 1011 appears to be an ideal radiopharmaceutical for evaluation of ventricular function and myocardial perfusion.

Mast cells contribute to scar formation during fetal wound healing.

PubMed

Wulff, Brian C; Parent, Allison E; Meleski, Melissa A; DiPietro, Luisa A; Schrementi, Megan E; Wilgus, Traci A

2012-02-01

Scar formation is a potentially detrimental process of tissue restoration in adults, affecting organ form and function. During fetal development, cutaneous wounds heal without inflammation or scarring at early stages of development; however, they begin to heal with significant inflammation and scarring as the skin becomes more mature. One possible cell type that could regulate the change from scarless to fibrotic healing is the mast cell. We show here that dermal mast cells in scarless wounds generated at embryonic day 15 (E15) are fewer in number, less mature, and do not degranulate in response to wounding as effectively as mast cells of fibrotic wounds made at embryonic day 18 (E18). Differences were also observed between cultured mast cells from E15 and E18 skin, with regard to degranulation and preformed cytokine levels. Injection of mast cell lysates into E15 wounds disrupted scarless healing, suggesting that mast cells interfere with scarless repair. Finally, wounds produced at E18, which normally heal with a scar, healed with significantly smaller scars in mast cell-deficient Kit(W/W-v) mice compared with Kit(+/+) littermates. Together, these data suggest that mast cells enhance scar formation, and that these cells may mediate the transition from scarless to fibrotic healing during fetal development.

Automated segmentation of myocardial scar in late enhancement MRI using combined intensity and spatial information.

PubMed

Tao, Qian; Milles, Julien; Zeppenfeld, Katja; Lamb, Hildo J; Bax, Jeroen J; Reiber, Johan H C; van der Geest, Rob J

2010-08-01

Accurate assessment of the size and distribution of a myocardial infarction (MI) from late gadolinium enhancement (LGE) MRI is of significant prognostic value for postinfarction patients. In this paper, an automatic MI identification method combining both intensity and spatial information is presented in a clear framework of (i) initialization, (ii) false acceptance removal, and (iii) false rejection removal. The method was validated on LGE MR images of 20 chronic postinfarction patients, using manually traced MI contours from two independent observers as reference. Good agreement was observed between automatic and manual MI identification. Validation results showed that the average Dice indices, which describe the percentage of overlap between two regions, were 0.83 +/- 0.07 and 0.79 +/- 0.08 between the automatic identification and the manual tracing from observer 1 and observer 2, and the errors in estimated infarct percentage were 0.0 +/- 1.9% and 3.8 +/- 4.7% compared with observer 1 and observer 2. The difference between the automatic method and manual tracing is in the order of interobserver variation. In conclusion, the developed automatic method is accurate and robust in MI delineation, providing an objective tool for quantitative assessment of MI in LGE MR imaging.

Cardiac fibroblast GSK-3β regulates ventricular remodeling and dysfunction in ischemic heart

PubMed Central

Lal, Hind; Ahmad, Firdos; Zhou, Jibin; Yu, Justine E.; Vagnozzi, Ronald J.; Guo, Yuanjun; Yu, Daohai; Tsai, Emily J.; Woodgett, James; Gao, Erhe; Force, Thomas

2014-01-01

Background Myocardial infarction-induced remodeling includes chamber dilatation, contractile dysfunction, and fibrosis. Of these, fibrosis is the least understood. Following MI, activated cardiac fibroblasts (CFs) deposit extracellular matrix. Current therapies to prevent fibrosis are inadequate and new molecular targets are needed. Methods and Results Herein we report that GSK-3β is phosphorylated (inhibited) in fibrotic tissues from ischemic human and mouse heart. Using two fibroblast-specific GSK-3β knockout mouse models, we show that deletion of GSK-3β in CFs leads to fibrogenesis, left ventricular dysfunction and excessive scarring in the ischemic heart. Deletion of GSK-3β induces a pro-fibrotic myofibroblast phenotype in isolated CFs, in post-MI hearts, and in MEFs deleted for GSK-3β. Mechanistically, GSK-3β inhibits pro-fibrotic TGF-β1-SMAD-3 signaling via interactions with SMAD-3. Moreover, deletion of GSK-3β resulted in the suppression of SMAD-3 transcriptional activity. This pathway is central to the pathology since a small molecule inhibitor of SMAD-3 largely prevented fibrosis and limited LV remodeling. Conclusion These studies support targeting GSK-3β in myocardial fibrotic disorders and establish critical roles of CFs in remodeling and ventricular dysfunction. PMID:24899689

The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities

PubMed Central

Frangogiannis, Nikolaos G

2014-01-01

Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-Like Receptor (TLR)/Interleukin (IL)-1 signaling, resulting in activation of the Nuclear Factor (NF)-κB system and induction of chemokines, cytokines and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment and resolution of the post-infarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury. PMID:24072174

The Role of Cardiovascular Magnetic Resonance Imaging in Heart Failure

PubMed Central

Peterzan, Mark A; Rider, Oliver J

2016-01-01

Cardiovascular imaging is key for the assessment of patients with heart failure. Today, cardiovascular magnetic resonance imaging plays an established role in the assessment of patients with suspected and confirmed heart failure syndromes, in particular identifying aetiology. Its role in informing prognosis and guiding decisions around therapy are evolving. Key strengths include its accuracy; reproducibility; unrestricted field of view; lack of radiation; multiple abilities to characterise myocardial tissue, thrombus and scar; as well as unparalleled assessment of left and right ventricular volumes. T2* has an established role in the assessment and follow-up of iron overload cardiomyopathy and a role for T1 in specific therapies for cardiac amyloid and Anderson–Fabry disease is emerging. PMID:28785465

Role of left ventricular twist mechanics in cardiomyopathies, dance of the helices

PubMed Central

Kauer, Floris; Geleijnse, Marcel Leonard; van Dalen, Bastiaan Martijn

2015-01-01

Left ventricular twist is an essential part of left ventricular function. Nevertheless, knowledge is limited in “the cardiology community” as it comes to twist mechanics. Fortunately the development of speckle tracking echocardiography, allowing accurate, reproducible and rapid bedside assessment of left ventricular twist, has boosted the interest in this important mechanical aspect of left ventricular deformation. Although the fundamental physiological role of left ventricular twist is undisputable, the clinical relevance of assessment of left ventricular twist in cardiomyopathies still needs to be established. The fact remains; analysis of left ventricular twist mechanics has already provided substantial pathophysiological understanding on a comprehensive variety of cardiomyopathies. It has become clear that increased left ventricular twist in for example hypertrophic cardiomyopathy may be an early sign of subendocardial (microvascular) dysfunction. Furthermore, decreased left ventricular twist may be caused by left ventricular dilatation or an extensive myocardial scar. Finally, the detection of left ventricular rigid body rotation in noncompaction cardiomyopathy may provide an indispensible method to objectively confirm this difficult diagnosis. All this endorses the value of left ventricular twist in the field of cardiomyopathies and may further encourage the implementation of left ventricular twist parameters in the “diagnostic toolbox” for cardiomyopathies. PMID:26322187

Automated segmentation and reconstruction of patient-specific cardiac anatomy and pathology from in vivo MRI*

NASA Astrophysics Data System (ADS)

Ringenberg, Jordan; Deo, Makarand; Devabhaktuni, Vijay; Filgueiras-Rama, David; Pizarro, Gonzalo; Ibañez, Borja; Berenfeld, Omer; Boyers, Pamela; Gold, Jeffrey

2012-12-01

This paper presents an automated method to segment left ventricle (LV) tissues from functional and delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) scans using a sequential multi-step approach. First, a region of interest (ROI) is computed to create a subvolume around the LV using morphological operations and image arithmetic. From the subvolume, the myocardial contours are automatically delineated using difference of Gaussians (DoG) filters and GSV snakes. These contours are used as a mask to identify pathological tissues, such as fibrosis or scar, within the DE-MRI. The presented automated technique is able to accurately delineate the myocardium and identify the pathological tissue in patient sets. The results were validated by two expert cardiologists, and in one set the automated results are quantitatively and qualitatively compared with expert manual delineation. Furthermore, the method is patient-specific, performed on an entire patient MRI series. Thus, in addition to providing a quick analysis of individual MRI scans, the fully automated segmentation method is used for effectively tagging regions in order to reconstruct computerized patient-specific 3D cardiac models. These models can then be used in electrophysiological studies and surgical strategy planning.

Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair.

PubMed

Li, Haichang; Duann, Pu; Lin, Pei-Hui; Zhao, Li; Fan, Zhaobo; Tan, Tao; Zhou, Xinyu; Sun, Mingzhai; Fu, Minghuan; Orange, Matthew; Sermersheim, Matthew; Ma, Hanley; He, Duofen; Steinberg, Steven M; Higgins, Robert; Zhu, Hua; John, Elizabeth; Zeng, Chunyu; Guan, Jianjun; Ma, Jianjie

2015-10-02

Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53(-/-) mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

[Nuclear cardiology with new radiopharmaceuticals].

PubMed

Bunko, H

1994-08-01

In the field of nuclear cardiology, 99mTc labeled myocardial perfusion agents such as MIBI, Tetrofosmin and Teboroxime, 111In-antimyosin for imaging of myocardial necrosis, 123I-betamethyl-iodophenylpentadecanoic acid (BMIPP) for imaging of myocardial fatty acid metabolism and 123I-metaiodobenzylguanidine (MIBG) for imaging of myocardial adrenergic function are introduced recently in Japan. Improved image quality and simultaneous evaluation of myocardial perfusion, function and wall motion can be obtained with use of 99mTc labeled myocardial perfusion agents. 111In-antimyosin enables specific imaging of myocardial necrosis which leads to the use for wide variety of heart diseases. Discrepancy of the myocardial perfusion and metabolism in case of stunned myocardium or cardiomyopathy can be evaluated by 123I-BMIPP in conjunction with perfusion agent. Recently wide variety of diseases which may have cardiac adrenergic abnormality are targeted for 123I-MIBG imaging. These new radiopharmaceuticals are expected to be powerful tool for evaluation of the pathophysiology including severity and prognosis and evaluation of the etiology of the various heart diseases.

Electroactive 3D materials for cardiac tissue engineering

NASA Astrophysics Data System (ADS)

Gelmi, Amy; Zhang, Jiabin; Cieslar-Pobuda, Artur; Ljunngren, Monika K.; Los, Marek Jan; Rafat, Mehrdad; Jager, Edwin W. H.

2015-04-01

By-pass surgery and heart transplantation are traditionally used to restore the heart's functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

Imaging and Modeling of Myocardial Metabolism

PubMed Central

Jamshidi, Neema; Karimi, Afshin; Birgersdotter-Green, Ulrika; Hoh, Carl

2010-01-01

Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed. PMID:20559785

The Scarbase Duo(®): Intra-rater and inter-rater reliability and validity of a compact dual scar assessment tool.

PubMed

Fell, Matthew; Meirte, Jill; Anthonissen, Mieke; Maertens, Koen; Pleat, Jonathon; Moortgat, Peter

2016-03-01

Objective scar assessment tools were designed to help identify problematic scars and direct clinical management. Their use has been restricted by their measurement of a single scar property and the bulky size of equipment. The Scarbase Duo(®) was designed to assess both trans-epidermal water loss (TEWL) and colour of a burn scar whilst being compact and easy to use. Twenty patients with a burn scar were recruited and measurements taken using the Scarbase Duo(®) by two observers. The Scarbase Duo(®) measures TEWL via an open-chamber system and undertakes colorimetry via narrow-band spectrophotometry, producing values for relative erythema and melanin pigmentation. Validity was assessed by comparing the Scarbase Duo(®) against the Dermalab(®) and the Minolta Chromameter(®) respectively for TEWL and colorimetry measurements. The intra-class correlation coefficient (ICC) was used to assess reliability with standard error of measurement (SEM) used to assess reproducibility of measurements. The Pearson correlation coefficient (r) was used to assess the convergent validity. The Scarbase Duo(®) TEWL mode had excellent reliability when used on scars for both intra- (ICC=0.95) and inter-rater (ICC=0.96) measurements with moderate SEM values. The erythema component of the colorimetry mode showed good reliability for use on scars for both intra-(ICC=0.81) and inter-rater (ICC=0.83) measurements with low SEM values. Pigmentation values showed excellent reliability on scar tissue for both intra- (ICC=0.97) and inter-rater (ICC=0.97) with moderate SEM values. The Scarbase Duo(®) TEWL function had excellent correlation with the Dermalab(®) (r=0.93) whilst the colorimetry erythema value had moderate correlation with the Minolta Chromameter (r=0.72). The Scarbase Duo(®) is a reliable and objective scar assessment tool, which is specifically designed for burn scars. However, for clinical use, standardised measurement conditions are recommended. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Prediction of Scar Size in Rats Six Months after Burns Based on Early Post-injury Polarization-Sensitive Optical Frequency Domain Imaging

PubMed Central

Kravez, Eli; Villiger, Martin; Bouma, Brett; Yarmush, Martin; Yakhini, Zohar; Golberg, Alexander

2017-01-01

Hypertrophic scars remain a major clinical problem in the rehabilitation of burn survivors and lead to physical, aesthetic, functional, psychological, and social stresses. Prediction of healing outcome and scar formation is critical for deciding on the best treatment plan. Both subjective and objective scales have been devised to assess scar severity. Whereas scales of the first type preclude cross-comparison between observers, those of the second type are based on imaging modalities that either lack the ability to image individual layers of the scar or only provide very limited fields of view. To overcome these deficiencies, this work aimed at developing a predictive model of scar formation based on polarization sensitive optical frequency domain imaging (PS-OFDI), which offers comprehensive subsurface imaging. We report on a linear regression model that predicts the size of a scar 6 months after third-degree burn injuries in rats based on early post-injury PS-OFDI and measurements of scar area. When predicting the scar area at month 6 based on the homogeneity and the degree of polarization (DOP), which are signatures derived from the PS-OFDI signal, together with the scar area measured at months 2 and 3, we achieved predictions with a Pearson coefficient of 0.57 (p < 10−4) and a Spearman coefficient of 0.66 (p < 10−5), which were significant in comparison to prediction models trained on randomly shuffled data. As the model in this study was developed on the rat burn model, the methodology can be used in larger studies that are more relevant to humans; however, the actual model inferred herein is not translatable. Nevertheless, our analysis and modeling methodology can be extended to perform larger wound healing studies in different contexts. This study opens new possibilities for quantitative and objective assessment of scar severity that could help to determine the optimal course of therapy. PMID:29249978

Identifying genes that extend life span using a high-throughput screening system.

PubMed

Chen, Cuiying; Contreras, Roland

2007-01-01

We developed a high-throughput functional genomic screening system that allows identification of genes prolonging lifespan in the baker's yeast Saccharomyces cerevisiae. The method is based on isolating yeast mother cells with a higher than average number of cell divisions as indicated by the number of bud scars on their surface. Fluorescently labeled wheat germ agglutinin (WGA) was used for specific staining of chitin, a major component of bud scars. The critical new steps in our bud-scar-sorting system are the use of small microbeads, which allows successive rounds of purification and regrowth of the mother cells (M-cell), and utilization of flow cytometry to sort and isolate cells with a longer lifespan based on the number of bud scars specifically labeled with WGA.

Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring

PubMed Central

Ahadome, Sarah D.; Abraham, David J.; Rayapureddi, Suryanarayana; Saw, Valerie P.; Saban, Daniel R.; Calder, Virginia L.; Norman, Jill T.; Ponticos, Markella; Daniels, Julie T.; Dart, John K.

2016-01-01

Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase family 1 (ALDH1) is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease (AED), used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential and readily translatable antifibrotic therapy. PMID:27699226

Prediction of myocardial functional recovery by noninvasive evaluation of Basal and hyperemic coronary flow in patients with previous myocardial infarction.

PubMed

Djordjevic-Dikic, Ana; Beleslin, Branko; Stepanovic, Jelena; Giga, Vojislav; Tesic, Milorad; Dobric, Milan; Stojkovic, Sinisa; Nedeljkovic, Milan; Vukcevic, Vladan; Dikic, Nenad; Petrasinovic, Zorica; Nedeljkovic, Ivana; Tomasevic, Miloje; Vujisic-Tesic, Bosiljka; Ostojic, Miodrag

2011-05-01

The aim of this study was to evaluate the relation of basal and hyperemic coronary flow with myocardial functional improvement in patients with previous myocardial infarction undergoing elective percutaneous coronary intervention (PCI). Coronary flow was measured using transthoracic Doppler echocardiography in 50 patients (41 men; mean age, 53 ± 8 years) with previous myocardial infarction before, 24 hours, and 3 months after elective PCI. Diastolic deceleration time (DDT) was measured from the peak diastolic velocity to the point of intercept of initial decay slope with baseline. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal peak diastolic flow velocities. In comparison with patients without improvements in left ventricular function, patients with recovered left ventricular function had longer DDTs before angioplasty (841 ± 286 vs. 435 ± 80 msec, P < .001). CFR was significantly higher in recovered compared with nonrecovered patients (2.60 ± 0.70 vs. 2.16 ± 0.34, P = .034) 24 hours after PCI. Global and regional wall motion scores before PCI, end-diastolic and end-systolic volumes, and CFR 24 hours after PCI and DDT before PCI were univariate predictors of left ventricular functional recovery. By multivariate analysis, DDT and regional wall motion score before PCI were independent predictors of left ventricular recovery in the follow-up period (P = .003 and P = .007, respectively). In patients with previous myocardial infarction undergoing elective PCI, evaluation of basal coronary flow pattern and measurement of DDT before angioplasty may predict functional improvement of myocardium in the follow-up period and could be useful quantitative parameters in the evaluation of potential improvement in myocardial function. Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Drosophila Kette coordinates myoblast junction dissolution and the ratio of Scar-to-WASp during myoblast fusion

PubMed Central

Hamp, Julia; Löwer, Andreas; Dottermusch-Heidel, Christine; Beck, Lothar; Moussian, Bernard; Flötenmeyer, Matthias

2016-01-01

ABSTRACT The fusion of founder cells and fusion-competent myoblasts (FCMs) is crucial for muscle formation in Drosophila. Characteristic events of myoblast fusion include the recognition and adhesion of myoblasts, and the formation of branched F-actin by the Arp2/3 complex at the site of cell–cell contact. At the ultrastructural level, these events are reflected by the appearance of finger-like protrusions and electron-dense plaques that appear prior to fusion. Severe defects in myoblast fusion are caused by the loss of Kette (a homolog of Nap1 and Hem-2, also known as NCKAP1 and NCKAP1L, respectively), a member of the regulatory complex formed by Scar or WAVE proteins (represented by the single protein, Scar, in flies). kette mutants form finger-like protrusions, but the electron-dense plaques are extended. Here, we show that the electron-dense plaques in wild-type and kette mutant myoblasts resemble other electron-dense structures that are known to function as cellular junctions. Furthermore, analysis of double mutants and attempts to rescue the kette mutant phenotype with N-cadherin, wasp and genes of members of the regulatory Scar complex revealed that Kette has two functions during myoblast fusion. First, Kette controls the dissolution of electron-dense plaques. Second, Kette controls the ratio of the Arp2/3 activators Scar and WASp in FCMs. PMID:27521427

Cardiorespiratory fitness modifies the relationship between myocardial function and cerebral blood flow in older adults.

PubMed

Johnson, Nathan F; Gold, Brian T; Bailey, Alison L; Clasey, Jody L; Hakun, Jonathan G; White, Matthew; Long, Doug E; Powell, David K

2016-05-01

A growing body of evidence indicates that cardiorespiratory fitness attenuates some age-related cerebral declines. However, little is known about the role that myocardial function plays in this relationship. Brain regions with high resting metabolic rates, such as the default mode network (DMN), may be especially vulnerable to age-related declines in myocardial functions affecting cerebral blood flow (CBF). This study explored the relationship between a measure of myocardial mechanics, global longitudinal strain (GLS), and CBF to the DMN. In addition, we explored how cardiorespiratory affects this relationship. Participants were 30 older adults between the ages of 59 and 69 (mean age=63.73years, SD=2.8). Results indicated that superior cardiorespiratory fitness and myocardial mechanics were positively associated with DMN CBF. Moreover, results of a mediation analysis revealed that the relationship between GLS and DMN CBF was accounted for by individual differences in fitness. Findings suggest that benefits of healthy heart function to brain function are modified by fitness. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

PubMed

Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

2016-05-15

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function. Copyright © 2016 Elsevier Inc. All rights reserved.

Myocardial perfusion and left ventricular function indices assessed by gated myocardial perfusion SPECT in methamphetamine abusers.

PubMed

Dadpour, Bita; Dabbagh Kakhki, Vahid R; Afshari, Reza; Dorri-Giv, Masoumeh; Mohajeri, Seyed A R; Ghahremani, Somayeh

2016-12-01

Methamphetamine (MA) is associated with alterations of cardiac structure and function, although it is less known. In this study, we assessed possible abnormality in myocardial perfusion and left ventricular function using gated myocardial perfusion SPECT. Fifteen patients with MA abuse, on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) MA dependency determined by Structured Clinical Interview for DSM-IV, underwent 2-day dipyridamole stress/rest Tc-sestamibi gated myocardial perfusion SPECT. An average daily dose of MA use was 0.91±1.1 (0.2-4) g. The duration of MA use was 3.4±2.1 (1-7) years. In visual and semiquantitative analyses, all patients had normal gated myocardial perfusion SPECT, with no perfusion defects. In all gated SPECT images, there was no abnormality in left ventricular wall motion and thickening. All summed stress scores and summed rest scores were below 3. Calculated left ventricular functional indices including the end-diastolic volume, end-systolic volume, and left ventricular ejection fraction were normal. Many cardiac findings because of MA mentioned in previous reports are less likely because of significant epicardial coronary artery stenosis.

Evaluation of effect of atorvastatin on left ventricular systolic function in rats with myocardial infarction via 2D-STI technique.

PubMed

Hua, Yan; Xie, Manying; Yin, Jiabao; Wang, Yu; Gan, Ling; Sang, Ming; Sun, Xiaodong; Li, Mingyang; Liu, Shanjun; Xu, Jinzhi

2018-05-01

This report aims to evaluate the effect of atorvastatin (Ator) on left ventricular systolic function in myocardial infarction (MI) rats. Forty healthy adult Sprague-Dawley rats were randomly divided into four groups: Ator group, MI group, sham-operation group and normal group. The left anterior descending coronary arteries were ligated to establish the MI model; after modeling, the Ator group was treated with Ator for 4 consecutive weeks. The echocardiographic detection was performed; the left ventricular myocardial systolic peak velocities, strain and strain rates were analyzed using the 2D-STI technique. After 4 weeks, myocardial tissues were taken from all rats and received the pathological examination. Left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) in Ator group and MI group were increased after operation, but left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were decreased; myocardial function were decreased significantly (p<0.05). After Ator treatment, myocardial function at the 3rd and 4th week after operation increased significantly (p<0.05). After Ator treatment, LVEDD and LVESD decreased while LVEF and LVFS increased in Ator group at the 3rd and 4th week after operation compared with MI group (p<0.05). At the 4th week after operation, LVEDD and LVESD in Ator group were decreased compared with those at the 1st and 2nd week after operation, but LVEF and LVFS were increased compared with those at the 1st, 2nd and 3rd week after operation (p<0.05). Pathological examination showed that necrosis and fibrosis of myocardial cells and inflammatory reaction were obvious in MI group. The inflammatory reaction of myocardial cells and myocardial fibrosis were lighter in Ator group. Ator can effectively improve the left ventricular systolic function in MI rats, which could be related to the reduction of response to inflammation and fibrosis.

Pericardial application as a new route for implanting stem-cell cardiospheres to treat myocardial infarction.

PubMed

Zhang, Jianhua; Wu, Zheng; Fan, Zepei; Qin, Zixi; Wang, Yingwei; Chen, Jiayuan; Wu, Maoxiong; Chen, Yangxin; Wu, Changhao; Wang, Jingfeng

2018-06-01

Cardiospheres (CSps) are a promising new form of cardiac stem cells with advantage over other stem cells for myocardial regeneration, but direct implantation of CSps by conventional routes has been limited due to potential embolism. We have implanted CSps into the pericardial cavity and systematically demonstrated its efficacy regarding myocardial infarction. Stem cell potency and cell viability can be optimized in vitro prior to implantation by pre-conditioning CSps with pericardial fluid and hydrogel packing. Transplantation of optimized CSps into the pericardial cavity improved cardiac function and alleviated myocardial fibrosis, increased myocardial cell survival and promoted angiogenesis. Mechanistically, CSps are able to directly differentiate into cardiomyocytes in vivo and promote regeneration of myocardial cells and blood vessels through a paracrine effect with released growth factors as potential paracrine mediators. These findings establish a new strategy for therapeutic myocardial regeneration to treat myocardial infarction. Cardiospheres (CSps) are a new form of cardiac stem cells with an advantage over other stem cells for myocardial regeneration. However, direct implantation of CSps by conventional routes to treat myocardial infarction has been limited due to potential embolism. We have implanted CSps into the pericardial cavity and systematically assessed its efficacy on myocardial infarction. Preconditioning with pericardial fluid enhanced the activity of CSps and matrix hydrogel prolonged their viability. This shows that pretransplant optimization of stem cell potency and maintenance of cell viability can be achieved with CSps. Transplantation of optimized CSps into the pericardial cavity improved cardiac function and alleviated myocardial fibrosis in the non-infarcted area, and increased myocardial cell survival and promoted angiogenesis in the infarcted area. Mechanistically, CSps were able to directly differentiate into cardiomyocytes in vivo and promoted regeneration of myocardial cells and blood vessels in the infarcted area through a paracrine effect with released growth factors in pericardial cavity serving as possible paracrine mediators. This is the first demonstration of direct pericardial administration of pre-optimized CSps, and its effectiveness on myocardial infarction by functional and morphological outcomes with distinct mechanisms. These findings establish a new strategy for therapeutic myocardial regeneration to treat myocardial infarction. © 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Transplantation of marrow-derived cardiac stem cells carried in fibrin improves cardiac function after myocardial infarction.

PubMed

Guo, Hai-Dong; Wang, Hai-Jie; Tan, Yu-Zhen; Wu, Jin-Hong

2011-01-01

The high death rate of the transplanted stem cells in the infarcted heart and the low efficiency of differentiation toward cardiomyocytes influence the outcome of stem cell transplantation for treatment of myocardial infarction (MI). Fibrin glue (FG) has been extensively used as a cell implantation matrix to increase cell survival. However, mechanisms of the effects of FG for stem cell transplantation to improve cardiac function are unclear. We have isolated c-kit+/Sca-1+ marrow-derived cardiac stem cells (MCSCs) from rat bone marrow; the cells expressed weakly early cardiac transcription factor Nkx2.5, GATA-4, Mef2C, and Tbx5. Effects of FG on survival, proliferation, and migration of MCSCs were examined in vitro. Cytoprotective effects of FG were assessed by exposure of MCSCs to anoxia. Efficacy of MCSC transplantation in FG was evaluated in the female rat MI model. The MCSCs survived well and proliferated in FG, and they may migrate out from the edge of FG in the wound and nature state. Acridine orange/ethidium bromide staining and lactate dehydrogenase analysis showed that MCSCs in FG were more resistant to anoxia as compared with MCSCs alone. In a rat MI model, cardiac function was improved and scar area was obviously reduced in group of MCSCs in FG compared with group of MCSCs and FG alone, respectively. Y chromosome fluorescence in situ hybridization showed that there were more survived MCSCs in group of MCSCs in FG than those in group of MCSCs alone, and most Y chromosome positive cells expressed cardiac troponin T (cTnT) and connexin-43 (Cx-43). Cx-43 was located between Y chromosome positive cells and recipient cardiomyocytes. Microvessel density in the peri-infarct regions and infarct regions significantly increased in group of MCSCs in FG. These results suggest that FG provide a suitable microenvironment for survival and proliferation of MCSCs and protect cells from apoptosis and necrosis caused by anoxia. MCSCs could differentiate into cardiomyocytes after being transplanted in the border of the infarcted myocardium and form connections with native cardiomyocytes. FG is helpful for MCSC transplantation to repair myocardium and improve cardiac function through promoting the survival, migration, and cardiomyogenic differentiation of MCSCs and inducing angiogenesis.

Illness consequences after myocardial infarction: problems with physical functioning and return to work.

PubMed

Brink, Eva; Brändström, Yvonne; Cliffordsson, Christina; Herlitz, Johan; Karlson, Björn W

2008-12-01

This paper is a report of a study to explore health problems, physical and mental functioning, and physical activity in working-age patients after myocardial infarction, in order to assess the possible effects of these factors on return to work. A diagnosis of myocardial infarction may discourage patients from continuing an active working life. Enabling myocardial infarction patients to return to work has benefits for both individuals and society. A convenience sample was recruited of 88 patients,

Effects of glutamine treatment on myocardial damage and cardiac function in rats after severe burn injury.

PubMed

Yan, Hong; Zhang, Yong; Lv, Shang-jun; Wang, Lin; Liang, Guang-ping; Wan, Qian-xue; Peng, Xi

2012-01-01

Treatment with glutamine has been shown to reduce myocardial damage associated with ischemia/reperfusion injury. However, the cardioprotective effect of glutamine specifically after burn injury remains unclear. The present study explores the ability of glutamine to protect against myocardial damage in rats that have been severely burned. Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B) and a glutamine-treated group (G). Groups B and G were subjected to full thickness burns comprising 30% of total body surface area. Group G was administered 1.5 g/ (kg•d) glutamine and group B was given the same dose of alanine via intragastric administration for 3 days. Levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and blood lactic acid were measured, as well as myocardial ATP and glutathione (GSH) contents. Cardiac function indices and histopathological changes were analyzed at 12, 24, 48 and 72 post-burn hours. In both burned groups, levels of serum CK, LDH, AST and blood lactic acid increased significantly, while myocardial ATP and GSH contents decreased. Compared with group B, CK, LDH, and AST levels were lower and blood lactic acid, myocardial ATP and GSH levels were higher in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage were significantly reduced in group G compared to B. Taken together, these results show that glutamine supplementation protects myocardial structure and function after burn injury by improving energy metabolism and by promoted the synthesis of ATP and GSH in cardiac myocytes.

Effects of glutamine treatment on myocardial damage and cardiac function in rats after severe burn injury

PubMed Central

Yan, Hong; Zhang, Yong; Lv, Shang-jun; Wang, Lin; Liang, Guang-ping; Wan, Qian-xue; Peng, Xi

2012-01-01

Treatment with glutamine has been shown to reduce myocardial damage associated with ischemia/reperfusion injury. However, the cardioprotective effect of glutamine specifically after burn injury remains unclear. The present study explores the ability of glutamine to protect against myocardial damage in rats that have been severely burned. Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B) and a glutamine-treated group (G). Groups B and G were subjected to full thickness burns comprising 30% of total body surface area. Group G was administered 1.5 g/ (kg•d) glutamine and group B was given the same dose of alanine via intragastric administration for 3 days. Levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and blood lactic acid were measured, as well as myocardial ATP and glutathione (GSH) contents. Cardiac function indices and histopathological changes were analyzed at 12, 24, 48 and 72 post-burn hours. In both burned groups, levels of serum CK, LDH, AST and blood lactic acid increased significantly, while myocardial ATP and GSH contents decreased. Compared with group B, CK, LDH, and AST levels were lower and blood lactic acid, myocardial ATP and GSH levels were higher in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage were significantly reduced in group G compared to B. Taken together, these results show that glutamine supplementation protects myocardial structure and function after burn injury by improving energy metabolism and by promotedthe synthesis of ATP and GSH in cardiac myocytes. PMID:22977661

Effect of cold air inhalation and isometric exercise on coronary blood flow and myocardial function in humans

PubMed Central

Muller, Matthew D.; Gao, Zhaohui; Drew, Rachel C.; Herr, Michael D.; Leuenberger, Urs A.

2011-01-01

The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold + grip protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial function (tissue Doppler imaging), O2 saturation, and pulmonary function were measured. The rate-pressure product (RPP) was used as an index of myocardial O2 demand, whereas CBV was used as an index of myocardial O2 supply. Compared with the sham protocol, the cold air protocol caused a significantly higher RPP, but there was a significant reduction in CBV. The cold + grip protocol caused a significantly greater increase in RPP compared with the grip protocol (P = 0.045), but the increase in CBV was significantly less (P = 0.039). However, myocardial function was not impaired during the cold + grip protocol relative to the grip protocol alone. Collectively, these data indicate that there is a supply-demand mismatch in the coronary vascular bed when cold ambient air is breathed during acute exertion but myocardial function is preserved, suggesting an adequate redistribution of blood flow. PMID:21940852

Sepiapterin reduces postischemic injury in the rat heart.

PubMed

Tiefenbacher, Christiane P; Lee, Ching-Hua; Kapitza, Jolanthe; Dietz, Volker; Niroomand, Feraydoon

2003-10-01

A reduced availability of tetrahydrobiopterin (BH4), an essential cofactor for NO-synthesis, is causally involved in the development of endothelial dysfunction associated with ischemia/reperfusion. We, therefore, investigated the effect of sepiapterin, a substrate for BH4 synthesis, on postischemic injury in myocardial infarction and myocardial stunning. In rats, myocardial stunning was induced by repetitive ischemia (5 x 10-min ligature of the left coronary artery, 5 x 20-min reperfusion) and myocardial infarction by 50-min ligature and 60-min reperfusion. Myocardial blood flow was determined by H2-clearance, regional myocardial function by pulsed Doppler and infarct size by tetrazolium staining. Myeloperoxidase (MPO) activity was measured as a marker of neutrophil extravasation. cGMP was determined in rat serum as an indicator of increased NO synthesis. In animals treated with sepiapterin, regional myocardial function was significantly improved in both myocardial stunning and infarction and infarct size was significantly reduced. MPO activity decreased with sepiapterin treatment in both models. The systemic level of cGMP was reduced both following myocardial stunning and myocardial infarction in the control group. Pretreatment with sepiapterin induced a significant increase of cGMP level at the end of the protocol in both models. Substitution of sepiapterin reduces postischemic injury both in myocardial stunning and infarction apparently by ameliorating the availability of NO, thereby attenuating the activation of neutrophils in ischemia/reperfusion.

Reactivation of the Nkx2.5 cardiac enhancer after myocardial infarction does not presage myogenesis.

PubMed

Deutsch, Marcus-André; Doppler, Stefanie A; Li, Xinghai; Lahm, Harald; Santamaria, Gianluca; Cuda, Giovanni; Eichhorn, Stefan; Ratschiller, Thomas; Dzilic, Elda; Dreßen, Martina; Eckart, Annekathrin; Stark, Konstantin; Massberg, Steffen; Bartels, Anna; Rischpler, Christoph; Gilsbach, Ralf; Hein, Lutz; Fleischmann, Bernd K; Wu, Sean M; Lange, Rüdiger; Krane, Markus

2018-03-20

The contribution of resident stem or progenitor cells to cardiomyocyte renewal after injury in adult mammalian hearts remains a matter of considerable debate. We evaluated a cell population in the adult mouse heart induced by myocardial infarction (MI) and characterized by an activated Nkx2.5 enhancer element that is specific for multipotent cardiac progenitor cells during embryonic development. We hypothesized that these MI induced cells (MICs) harbor cardiomyogenic properties similar to their embryonic counterparts. MICs reside in the heart and mainly localize to the infarction area and border zone. Interestingly, gene expression profiling of purified MICs one week after infarction revealed increased expression of stem cell markers and embryonic cardiac transcription factors in these cells as compared to the non-mycoyte cell fraction of adult hearts. A subsequent global transcriptome comparison with embryonic cardiac progenitor cells and fibroblasts and in vitro culture of MICs unveiled that (myo-) fibroblastic features predominated and that cardiac transcription factors were only expressed at background levels. Adult injury induced reactivation of a cardiac-specific Nkx2.5 enhancer element known to specifically mark myocardial progenitor cells during embryonic development does not reflect hypothesized embryonic cardiomyogenic properties. Our data suggest a decreasing plasticity of cardiac progenitor (-like) cell populations with increasing age. A re-expression of embryonic, stem or progenitor cell features in the adult heart must be interpreted very carefully with respect to the definition of cardiac resident progenitor cells. Albeit, the abundance of scar formation after cardiac injury suggests a potential to target predestinated activated profibrotic cells to push them towards cardiomyogenic differentiation to improve regeneration.

Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy.

PubMed

Beer, Meinrad; Weidemann, Frank; Breunig, Frank; Knoll, Anita; Koeppe, Sabrina; Machann, Wolfram; Hahn, Dietbert; Wanner, Christoph; Strotmann, Jörg; Sandstede, Jörn

2006-05-15

The present study evaluated the evolution of cardiac morphology, function, and late enhancement as a noninvasive marker of myocardial fibrosis, and their inter-relation during enzyme replacement therapy in patients with Fabry's disease using magnetic resonance imaging and color Doppler myocardial imaging. Late enhancement, which was present in up to 50% of patients, was associated with increased left ventricular mass, the failure of a significant regression of hypertrophy during enzyme replacement therapy, and worse segmental myocardial function. Late enhancement may predict the effect of enzyme replacement therapy on left ventricular mass and cardiac function.

[Rupture of lateral ligaments of the ankle joint: MR imaging before and after functional therapy].

PubMed

Grebe, P; Kreitner, K F; Roeder, W; Kersjes, W; Hennes, R; Runkel, M

1995-09-01

Documentation via MRI of the healing of ruptured lateral collateral ankle ligaments after functional therapy. 35 patients with ankle sprain were examined by MRI and stress radiographs, 13 were operated afterwards, 22 patients underwent a functional conservative therapy and were examined by MRI and stress radiographs and second time after three months. MRI reports were correct in 12 of 13 operated cases. After conservative therapy we did not find any disrupted ankle ligament. MRI showed intact ligaments thickened by scar. MRI is able to show injuries of the lateral collateral ankle ligaments and demonstrates the healing by scar after conservative therapy.

Norepinephrine turnover in heart and spleen of 7-, 22-, and 34 C-acclimated hamsters

NASA Technical Reports Server (NTRS)

Jones, S. B.; Musacchia, X. J.

1976-01-01

The relationship of norepinephrine (NE) concentration and endogenous turnover rates in both myocardial and spleen tissues in the golden hamster is examined as a function of chronic exposure to either high or low ambient temperatures. Changes in myocardial and spleen NE turnover values are discussed in terms of functional alterations in sympathetic nerve activity and the importance of such changes in temperature acclimation. It is found that acclimation of hamsters to 7 C for 7-10 weeks results in decreased myocardial NE concentration and an apparent increase in myocardial NE turnover. In contrast, exposure to 34 C for 6-8 weeks results in increased myocardial NE concentration and an apparent decrease in NE turnover in both myocardial and spleen tissues. The implication of altered NE synthesis is that sympathetic nerve activity is reduced with heat acclimation and is enhanced with cold acclimation.

Reduction of myocardial blood flow reserve in idiopathic dilated cardiomyopathy without overt heart failure and its relation with functional indices: an echo-Doppler and positron emission tomography study.

PubMed

Morales, Maria-Aurora; Neglia, Danilo; L'Abbate, Antonio

2008-08-01

Myocardial blood flow during pharmacological vasodilatation is depressed in patients with idiopathic dilated cardiomyopathy even the in absence of overt heart failure; the extent of myocardial blood flow abnormalities is not predictable by left ventricular ejection fraction (LVEF) and diastolic dimensions. To assess whether myocardial blood flow impairment in idiopathic dilated cardiomyopathy without overt heart failure can be related to Doppler-derived dP/dt and to echocardiographically determined left ventricular end systolic stress - which is linked to myocardial blood flow reserve in advanced disease. Twenty-six patients, New York Heart Association Class I-II, (LVEF 37.4 +/- 1.4%, left ventricular diastolic dimensions 62.6 +/- 0.9 mm) underwent resting/dipyridamole [13N]NH3 flow positron emission tomography and an ultrasonic study. Regional myocardial blood flow values (ml/min per g) were computed from positron emission tomography data in 13 left ventricular (LV) myocardial regions and averaged to provide mean myocardial blood flow and myocardial blood flow reserve, defined as dipyridamole/resting mean myocardial blood flow ratio. Resting myocardial blood flow was 0.686 +/- 0.045, dipyridamole myocardial blood flow 1.39 +/- 0.15 and myocardial blood flow reserve 2.12 +/- 0.2, lower than in controls (P < 0.01). The ratio dP/dt was directly related to dipyridamole myocardial blood flow and myocardial blood flow reserve (r = 0.552 and 0.703, P < 0.005 and P < 0.0001); no relation was found between myocardial blood flow and LVEF left ventricular diastolic dimensions, and left ventricular end systolic stress. In idiopathic dilated cardiomyopathy patients without overt heart failure, the extent of myocardial blood flow reserve impairment is related to dP/dt but not to more classical indices of left ventricular function.

Intramyocardial bone marrow mononuclear cell transplantation in ischemic heart failure: Long-term follow-up.

PubMed

Lehtinen, Miia; Pätilä, Tommi; Kankuri, Esko; Lauerma, Kirsi; Sinisalo, Juha; Laine, Mika; Kupari, Markku; Vento, Antti; Harjula, Ari

2015-07-01

Long-term results regarding treatment of chronic ischemic heart failure with bone marrow mononuclear cells (BMMCs) have been few. We received encouraging results at the 1-year follow-up of patients treated with combined coronary artery bypass grafting (CABG) and BMMCs, so we decided to extend the follow-up. The study patients had received injections of BMMCs or vehicle into the myocardial infarction border area during CABG in a randomized and double-blind manner. We could contact 36 of the 39 patients recruited for the original study. Pre-operatively and after an extended follow-up period, we performed magnetic resonance imaging, measured pro-B-type amino-terminal natriuretic peptide, reviewed patient records from the follow-up period, and determined current quality of life with the Medical Outcomes Study Short-Form 36 (SF-36) Health Survey. The median follow-up time was 60.7 months (interquartile range [IQR], 45.1-72.6 months). No statistically significant difference was detected in change of pro-B-type amino-terminal natriuretic peptide values or in quality of life between groups. The median change in left ventricular ejection fraction was 4.9% (IQR, -2.1% to 12.3%) for controls and 3.9% (IQR, -5.2% to 10.2%) for the BMMC group (p = 0.647). Wall thickening in injected segments increased by a median of 17% (IQR, -5% to 30%) for controls and 15% (IQR, -12% to 19%) for BMMC patients (p = 0.434). Scar size in injected segments increased by a median of 2% (IQR, -7% to 19%) for controls but diminished for BMMC patients, with a median change of -17% (IQR, -30% to -6%; p = 0.011). In the treatment of chronic ischemic heart failure, combining intramyocardial BMMC therapy with CABG fails to affect cardiac function but can sustainably reduce scar size, even in the long-term. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Temporal deformation pattern in acute and late phases of ST-elevation myocardial infarction: incremental value of longitudinal post-systolic strain to assess myocardial viability.

PubMed

Huttin, Olivier; Marie, Pierre-Yves; Benichou, Maxime; Bozec, Erwan; Lemoine, Simon; Mandry, Damien; Juillière, Yves; Sadoul, Nicolas; Micard, Emilien; Duarte, Kevin; Beaumont, Marine; Rossignol, Patrick; Girerd, Nicolas; Selton-Suty, Christine

2016-10-01

Identification of transmural extent and degree of non-viability after ST-segment elevation myocardial infarction (STEMI) is clinically important. The objective of the present study was to assess the regional mechanics and temporal deformation patterns using speckle tracking echocardiography (STE) in acute and later phases of STEMI to predict myocardial damage in these patients. Ninety-eight patients with first STEMI underwent both echocardiography and cardiac magnetic resonance imaging in acute phase and at 6 months follow-up with 2D STE-derived measurements of peak longitudinal strain (PLS), Pre-STretch index (PST) and post-systolic deformation index (PSI). For each segment, late gadolinium enhancement (LGE) was defined as transmural (LGE >66 %) or non-transmural (<66 %). Global deformation values were significantly correlated with LVEFCMR and infarct size at both visits. A significantly lower value of segmental PLS and higher PSI and PST in necrotic segments were observed comparatively to control, adjacent and remote segments. The best parameters to predict transmural extent in acute phase were PSI with a cutoff value of 8 % (AUC: 0.84) and PLS with a cutoff value of -13 % (AUC: 0.86). PST showed high specificity, but poor sensitivity in predicting transmural extent. More importantly, the addition of PSI and PST to PLS in acute phase was associated with improved prediction of viability at 6 months (integrated discrimination improvement 2.5 % p < 0.01; net reclassification improvement 27 %; p < 0.01). All systolic deformation values separated transmural from non-transmural scarring. PLS combined with additional information relative to post-systolic deformation appears to be the most informative parameters to predict the transmural extent of MI in the early and late phases of MI. http://clinicaltrials.gov/show/NCT01109225 ; NCT01109225.

Nuclear cardiac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slutsky, R.; Ashburn, W.L.

1982-01-01

The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques. (KRM)

Salinomycin and other polyether ionophores are a new class of antiscarring agent.

PubMed

Woeller, Collynn F; O'Loughlin, Charles W; Roztocil, Elisa; Feldon, Steven E; Phipps, Richard P

2015-02-06

Although scarring is a component of wound healing, excessive scar formation is a debilitating condition that results in pain, loss of tissue function, and even death. Many tissues, including the lungs, heart, skin, and eyes, can develop excessive scar tissue as a result of tissue injury, chronic inflammation, or autoimmune disease. Unfortunately, there are few, if any, effective treatments to prevent excess scarring, and new treatment strategies are needed. Using HEK293FT cells stably transfected with a TGFβ-dependent luciferase reporter, we performed a small molecule screen to identify novel compounds with antiscarring activity. We discovered that the polyether ionophore salinomycin potently inhibited the formation of scar-forming myofibroblasts. Salinomycin (250 nm) blocked TGFβ-dependent expression of the cardinal myofibroblast products α smooth muscle actin, calponin, and collagen in primary human fibroblasts without causing cell death. Salinomycin blocked phosphorylation and activation of TAK1 and p38, two proteins fundamentally involved in signaling myofibroblast and scar formation. Expression of constitutively active mitogen activated kinase kinase 6, which activates p38 MAPK, attenuated the ability of salinomycin to block myofibroblast formation, demonstrating that salinomycin targets the p38 kinase pathway to disrupt TGFβ signaling. These data identify salinomycin and other polyether ionophores as novel potential antiscarring therapeutics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Salinomycin and Other Polyether Ionophores Are a New Class of Antiscarring Agent*

PubMed Central

Woeller, Collynn F.; O'Loughlin, Charles W.; Roztocil, Elisa; Feldon, Steven E.; Phipps, Richard P.

2015-01-01

Although scarring is a component of wound healing, excessive scar formation is a debilitating condition that results in pain, loss of tissue function, and even death. Many tissues, including the lungs, heart, skin, and eyes, can develop excessive scar tissue as a result of tissue injury, chronic inflammation, or autoimmune disease. Unfortunately, there are few, if any, effective treatments to prevent excess scarring, and new treatment strategies are needed. Using HEK293FT cells stably transfected with a TGFβ-dependent luciferase reporter, we performed a small molecule screen to identify novel compounds with antiscarring activity. We discovered that the polyether ionophore salinomycin potently inhibited the formation of scar-forming myofibroblasts. Salinomycin (250 nm) blocked TGFβ-dependent expression of the cardinal myofibroblast products α smooth muscle actin, calponin, and collagen in primary human fibroblasts without causing cell death. Salinomycin blocked phosphorylation and activation of TAK1 and p38, two proteins fundamentally involved in signaling myofibroblast and scar formation. Expression of constitutively active mitogen activated kinase kinase 6, which activates p38 MAPK, attenuated the ability of salinomycin to block myofibroblast formation, demonstrating that salinomycin targets the p38 kinase pathway to disrupt TGFβ signaling. These data identify salinomycin and other polyether ionophores as novel potential antiscarring therapeutics. PMID:25538236

Both Selenium Deficiency and Modest Selenium Supplementation Lead to Myocardial Fibrosis in Mice via Effects on Redox-Methylation Balance

PubMed Central

Metes-Kosik, Nicole; Luptak, Ivan; DiBello, Patricia M.; Handy, Diane E.; Tang, Shiow-Shih; Zhi, Hui; Qin, Fuzhong; Jacobsen, Donald W.; Loscalzo, Joseph; Joseph, Jacob

2013-01-01

Scope Selenium has complex effects in vivo on multiple homeostatic mechanisms such as redox balance, methylation balance, and epigenesis, via its interaction with the methionine-homocysteine cycle. In this study, we examined the hypothesis that selenium status would modulate both redox and methylation balance and thereby modulate myocardial structure and function. Methods and Results We examined the effects of selenium deficient (<0.025 mg/kg), control (0.15 mg/kg), and selenium supplemented (0.5 mg/kg) diets on myocardial histology, biochemistry and function in adult C57/BL6 mice. Selenium deficiency led to reactive myocardial fibrosis and systolic dysfunction accompanied by increased myocardial oxidant stress. Selenium supplementation significantly reduced methylation potential, DNA methyltransferase activity and DNA methylation. In mice fed the supplemented diet, inspite of lower oxidant stress, myocardial matrix gene expression was significantly altered resulting in reactive myocardial fibrosis and diastolic dysfunction in the absence of myocardial hypertrophy. Conclusions Our results indicate that both selenium deficiency and modest selenium supplementation leads to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart. The crucial role selenium plays in maintaining the balance between redox and methylation pathways needs to be taken into account while optimizing selenium status for prevention and treatment of heart failure. PMID:23097236

Testing the vulnerability and scar models of self-esteem and depressive symptoms from adolescence to middle adulthood and across generations.

PubMed

Steiger, Andrea E; Fend, Helmut A; Allemand, Mathias

2015-02-01

The vulnerability model states that low self-esteem functions as a predictor for the development of depressive symptoms whereas the scar model assumes that these symptoms leave scars in individuals resulting in lower self-esteem. Both models have received empirical support, however, they have only been tested within individuals and not across generations (i.e., between family members). Thus, we tested the scope of these competing models by (a) investigating whether the effects hold from adolescence to middle adulthood (long-term vulnerability and scar effects), (b) whether the effects hold across generations (intergenerational vulnerability and scar effects), and (c) whether intergenerational effects are mediated by parental self-esteem and depressive symptoms and parent-child discord. We used longitudinal data from adolescence to middle adulthood (N = 1,359) and from Generation 1 adolescents (G1) to Generation 2 adolescents (G2) (N = 572 parent-child pairs). Results from latent cross-lagged regression analyses demonstrated that both adolescent self-esteem and depressive symptoms were prospectively related to adult self-esteem and depressive symptoms 3 decades later. That is, both the vulnerability and scar models are valid over decades with stronger effects for the vulnerability model. Across generations, we found a substantial direct transmission effect from G1 to G2 adolescent depressive symptoms but no evidence for the proposed intergenerational vulnerability and scar effect or for any of the proposed mediating mechanisms. PsycINFO Database Record (c) 2015 APA, all rights reserved.

THE REAL ESTATE OF MYOBLAST CARDIAC TRANSPLANTATION – NEGATIVE REMODELING IS ASSOCIATED WITH LOCATION

PubMed Central

McCue, Jonathan D.; Swingen, Cory; Feldberg, Tanya; Caron, Gabe; Kolb, Adam; Denucci, Christopher; Prabhu, Somnath; Motilall, Randy; Breviu, Brian; Taylor, Doris A.

2009-01-01

Background Skeletal myoblast (SKMB) transplantation has been proposed as a therapy for ischemic cardiomyopathy due to its possible role in myogenesis. The relative safety and efficacy based on location within scar is not known. We hypothesized that SKMB transplanted into peripheral scar (compared to central scar) would more effectively attenuate negative left ventricular (LV) remodeling but at the risk of arrhythmia. Methods 34 New Zealand White rabbits underwent mid-left anterior descending artery (LAD) ligation to produce a transmural LV infarction. One month after LAD ligation SKMBs were injected either in the scar center (n=13) or scar periphery (n=10) and compared to saline injection (n=11). Holter monitoring and MRI was performed pre-injection; Holter monitoring was continued until two weeks post injection, with follow-up MRI at one month. Results Centrally-treated animals demonstrated increased LV end systolic volume, end diastolic volume and mass that correlated with injected cell number. There was a trend toward attenuation of negative LV remodeling in peripherally-treated animals compared to vehicle. Significant late ectopy was seen in several centrally-injected animals with no late ectopy seen in peripherally-injected animals. Conclusions We noted untoward effects with respect to negative LV remodeling following central injection, suggesting that transplanted cell location with respect to scar may be a key factor in the safety and efficacy of SKMB cardiac transplantation. Administration of SKMBs into peripheral scar appears safe with a trend toward improved function in comparison to sham injection. PMID:18187097

Most mutations that cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16) destabilize the protein quality-control E3 ligase CHIP.

PubMed

Kanack, Adam J; Newsom, Oliver J; Scaglione, Kenneth Matthew

2018-02-23

The accumulation of misfolded proteins promotes protein aggregation and neuronal death in many neurodegenerative diseases. To counteract misfolded protein accumulation, neurons have pathways that recognize and refold or degrade aggregation-prone proteins. One U-box-containing E3 ligase, C terminus of Hsc70-interacting protein (CHIP), plays a key role in this process, targeting misfolded proteins for proteasomal degradation. CHIP plays a protective role in mouse models of neurodegenerative disease, and in humans, mutations in CHIP cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16), a fatal neurodegenerative disease characterized by truncal and limb ataxia that results in gait instability. Here, we systematically analyzed CHIP mutations that cause SCAR16 and found that most SCAR16 mutations destabilize CHIP. This destabilization caused mutation-specific defects in CHIP activity, including increased formation of soluble oligomers, decreased interactions with chaperones, diminished substrate ubiquitination, and reduced steady-state levels in cells. Consistent with decreased CHIP stability promoting its dysfunction in SCAR16, most mutant proteins recovered activity when the assays were performed below the mutants' melting temperature. Together, our results have uncovered the molecular basis of genetic defects in CHIP function that cause SCAR16. Our insights suggest that compounds that improve the thermostability of genetic CHIP variants may be beneficial for treating patients with SCAR16. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Positron Emission Tomography of the Heart

DOE R&D Accomplishments Database

Schelbert, H. R.; Phelps, M. E.; Kuhl, D. E.

1979-01-01

Positron emission computed tomography (PCT) represents an important new tool for the noninvasive evaluation and, more importantly, quantification of myocardial performance. Most currently available techniques permit assessment of only one aspect of cardiac function, i.e., myocardial perfusion by gamma scintillation camera imaging with Thallium-201 or left ventricular function by echocardiography or radionuclide angiocardiography. With PCT it may become possible to study all three major segments of myocardial performance, i.e., regional blood flow, mechanical function and, most importantly, myocardial metabolism. Each of these segments can either be evaluated separately or in combination. This report briefly describes the principles and technological advantages of the imaging device, reviews currently available radioactive tracers and how they can be employed for the assessment of flow, function and metabolism; and, lastly, discusses possible applications of PCT for the study of cardiac physiology or its potential role in the diagnosis of cardiac disease.

Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease.

PubMed

Granér, Marit; Nyman, Kristofer; Siren, Reijo; Pentikäinen, Markku O; Lundbom, Jesper; Hakkarainen, Antti; Lauerma, Kirsi; Lundbom, Nina; Nieminen, Markku S; Taskinen, Marja-Riitta

2015-01-01

Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study. © 2014 American Heart Association, Inc.

The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries.

PubMed

Kobayashi, Makoto; Ota, Shusuke; Terada, Satoshi; Kawakami, Yohei; Otsuka, Takanobu; Fu, Freddie H; Huard, Johnny

2016-12-01

Although muscle injuries tend to heal uneventfully in most cases, incomplete functional recovery commonly occurs as a result of scar tissue formation at the site of injury, even after treatment with muscle-derived stem cells (MDSCs). The transplantation of MDSCs in the presence of a transforming growth factor β1 (TGF-β1) antagonist (losartan) would result in decreased scar tissue formation and enhance muscle regeneration after contusion injuries in a mouse model. Controlled laboratory study. An animal model of muscle contusion was developed using the tibialis anterior muscle in 48 healthy mice at 8 to 10 weeks of age. After sustaining muscle contusion injuries, the mice were divided into 4 groups: (1) saline injection group (control group; n = 15), (2) MDSC transplantation group (MDSC group; n = 15), (3) MDSC transplantation plus oral losartan group (MDSC/losartan group; n = 15), and (4) healthy uninjured group (healthy group; n = 3). Losartan was administrated systemically beginning 3 days after injury and continued until the designated endpoint (1, 2, or 4 weeks after injury). MDSCs were transplanted 4 days after injury. Muscle regeneration and fibrotic scar formation were evaluated by histology, and the expression of follistatin, MyoD, Smad7, and Smad2/3 were analyzed by immunohistochemistry and reverse transcription polymerase chain reaction analysis. Functional recovery was measured via electrical stimulation of the peroneal nerve. When compared with MDSC transplantation alone, MDSC/losartan treatment resulted in significantly decreased scar formation, an increase in the number of regenerating myofibers, and improved functional recovery after muscle contusions. In support of these findings, the expression levels of Smad7 and MyoD were significantly increased in the group treated with both MDSCs and losartan. When compared with MDSCs alone, the simultaneous treatment of muscle contusions with MDSCs and losartan significantly reduced scar formation, increased the number of regenerating myofibers, and improved the functional recovery of muscle; these effects were caused, at least in part, by the losartan-mediated upregulation of Smad7 and MyoD. Increased levels of Smad7 and MyoD together reduced the deposition of scar tissue (via the inhibition of TGF-β1 by Smad7) and committed the transplanted MDSCs toward a myogenic lineage (via Smad7-regulated MyoD expression). The study findings contribute to the development of biological treatments to accelerate and improve the quality of muscle healing after injury. © 2016 The Author(s).

Effect of granulocyte colony stimulating EPC on cardiac function and myocardial energy expenditure in patients with heart failure after myocardial infarction.

PubMed

Zhao, Zilin; Luo, Jianchun; Ma, Lixian; Luo, Xia; Huang, Liangyan

2015-01-01

To study the changes of cardiac function and myocardial energy expenditure following treatment with granulocyte colony stimulating factor (G-CSF) in patients with heart failure after myocardial infarction. Thirty-eight patients with heart failure after myocardial infarction were randomized into G-CSF treatment group and control group. All the patients received conventional treatment (medication and interventional therapy), and the patients in treatment group were given additional G-CSF (600 μg/day) for 7 consecutive days. The plasma level of brain-type natriuretic peptide (BNP) and the number of endothelial progenitor cells (EPC) in the peripheral blood were detected before and at 7 days and 4 months after the treatment. The cardiac functions (LVEF, FS, LVIDs, PWTs, EDV, SV, ET) was evaluated by ultrasonic imaging before and at 2 weeks and 4 months after the treatment. The MEE and circumferential end-systolic wall stress (cESS) were calculated by correlation formula. The number of EPC was significantly higher in the treatment group than in the control group after the treatment especially at 7 days (P<0.01). In both groups, BNP level was lowered significantly after the treatment to recover the normal level (P<0.01). The cardiac functions and myocardial energy expenditure were improved in all the patients at 2 weeks and 4 months after the treatment, and the improvement was more obvious in the treatment group (P<0.05), especially in terms of the MEE and cESS was significantly lowered in the treatment group than in the control group after the treatment at 2 weeks (P<0.01), the LVEF and FS was significantly increased in the treatment group than in the control group after the treatment at 4 months (P<0.01). EPC mobilization by G-CSF can effectively improve the cardiac functions, lessen ventricular remodeling and reduce myocardial energy expenditure in patients with heart failure after myocardial infarction.

Atrial electromechanical delay and diastolic dysfunction in primary Sjögren syndrome.

PubMed

Akyel, Ahmet; Tavil, Yusuf; Tufan, Abdurrahman; Yayla, Cagri; Kaya, Arif; Tezcan, Mehme Engin; Ozturk, Mehmet Akif; Boyaci, Bulent

2012-10-06

In this study we aimed to investigate myocardial function and atrial electromechanical properties by conventional and tissue doppler echocardiography in patients with primary Sjögren syndrome. Forty patients with Sjögren syndrome (SS) and 25 age- and sex-matched healthy volunteers were enrolled in the study. Using transthoracic echocardiography, myocardial performance index and atrial electromechanical properties were measured. Basal characteristics were similar between two groups. Myocardial performance index values were disturbed in patients with Sjögren syndrome (0.41 vs. 0.32, p < 0.01). There was significant intraatrial (16.4±6.4, 5.0±4.5, p < 0.01) and interatrial (30.6±10.1, 15.4±5.9, p < 0.01) electromechanical delay in this patient group. Myocardial function is disturbed and there is significant atrial electromechanical delay in patients with primary SS. This study is the first to show altered myocardial function and atrial electromechanical properties in primary SS.

Long-Term Implanted cOFM Probe Causes Minimal Tissue Reaction in the Brain

PubMed Central

Hochmeister, Sonja; Asslaber, Martin; Kroath, Thomas; Pieber, Thomas R.; Sinner, Frank

2014-01-01

This study investigated the histological tissue reaction to long-term implanted cerebral open flow microperfusion (cOFM) probes in the frontal lobe of the rat brain. Most probe-based cerebral fluid sampling techniques are limited in application time due to the formation of a glial scar that hinders substance exchange between brain tissue and the probe. A glial scar not only functions as a diffusion barrier but also alters metabolism and signaling in extracellular brain fluid. cOFM is a recently developed probe-based technique to continuously sample extracellular brain fluid with an intact blood-brain barrier. After probe implantation, a 2 week healing period is needed for blood-brain barrier reestablishment. Therefore, cOFM probes need to stay in place and functional for at least 15 days after implantation to ensure functionality. Probe design and probe materials are optimized to evoke minimal tissue reaction even after a long implantation period. Qualitative and quantitative histological tissue analysis revealed no continuous glial scar formation around the cOFM probe 30 days after implantation and only a minor tissue reaction regardless of perfusion of the probe. PMID:24621608

Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

PubMed Central

Li, Hong-Peng; Komuta, Yukari; Kimura-Kuroda, Junko; van Kuppevelt, Toin H.

2013-01-01

Abstract Dermatan sulfate (DS) is synthesized from chondroitin sulfate (CS) by epimerization of glucuronic acid of CS to yield iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of glycosaminoglycan degrading enzymes into the lesion site. Two weeks after injury, fibrotic and glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic scar. Injection of chondroitinase ABC (ChABC), which degrades both CS and DS, completely suppressed the fibrotic scar formation, reduced the glial scar, and promoted the regeneration of dopaminergic axons. Injection of the DS-degrading enzyme chondroitinase B (ChB) also yielded similar results. By contrast, injection of chondroitinase AC (ChAC), a CS-degrading enzyme, did not suppress the fibrotic and glial scar formation, but reduced CS immunoreactivity and promoted the axonal regeneration. Addition of transforming growth factor-β1 (TGF-β1) to a co-culture of meningeal fibroblasts and cerebral astrocytes induces a fibrotic scar-like cell cluster. The effect of TGF-β1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-β1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after brain injury: DS is involved in the lesion scar formation, and CS inhibits axonal regeneration. PMID:23438307

Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model.

PubMed

Dash, Rajesh; Kim, Paul J; Matsuura, Yuka; Ikeno, Fumiaki; Metzler, Scott; Huang, Ngan F; Lyons, Jennifer K; Nguyen, Patricia K; Ge, Xiaohu; Foo, Cheryl Wong Po; McConnell, Michael V; Wu, Joseph C; Yeung, Alan C; Harnish, Phillip; Yang, Phillip C

2015-07-27

The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts. Twelve adult swine underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85±60%, control 8±10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24±8%, control 110±30%; P<0.05). The positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Effectiveness of Acellular Dermal Matrix on Autologous Split-Thickness Skin Graft in Treatment of Deep Tissue Defect: Esthetic Subjective and Objective Evaluation.

PubMed

Lee, Yoo Jung; Park, Myong Chul; Park, Dong Ha; Hahn, Hyung Min; Kim, Sue Min; Lee, Il Jae

2017-10-01

A split-thickness skin graft (STSG) is performed to cover a large full-thickness skin defect. Esthetic and functional deficits can result, and many studies have sought to overcome them. This study compared the effectiveness of the acellular dermal matrix (ADM) graft and STSG concerning esthetic and functional effectiveness of ADM on scar quality. Of the patients who underwent anterolateral thigh free flap from 2011 to 2015, patients who received skin graft only (n = 10) or skin graft with ADM (n = 20) for coverage of the donor site were enrolled. In all cases, autologous STSG was performed with 1:1.5 meshed 0.008-0.010-inch-thick skin. In the skin graft with ADM group, 0.008-0.013-inch-thick meshed ADM (CGderm ® ; CGBio, Inc., Seungnam, Korea) was co-grafted. Negative-pressure wound therapy (CuraVAC ® ; CGBio, Inc., Seungnam, Korea) was applied to both groups in continuous mode at -120 mmHg. We investigate early outcomes (skin loss rate, duration of negative-pressure wound therapy, days to removal of stitches, days to achieve complete healing, and complications) and late outcomes in terms of scar quality (vascularity, pigmentation, pliability and height) and graft-related symptoms (itching sensation and pain). Assessments used the Vancouver Scar Scale and the Patient and Observer Scar Assessment Scale. Skin fold was measured to evaluate the elasticity of scar tissue. In the Vancouver Scar Scale, vascularity subscore (p = 0.003) and total score (p = 0.016) were significantly lower in the skin graft with ADM group. In Patient and Observer Scar Assessment Scale, the pain (p = 0.037) and stiffness subscores (p = 0.002), and total score (p = 0.017) were significantly lower in the skin graft with ADM group. Skin graft with ADM results in better scar quality in objective and subjective aspects. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Initial shunt type at the Norwood operation impacts myocardial function in hypoplastic left heart syndrome.

PubMed

Ruotsalainen, Hanna K; Pihkala, Jaana; Salminen, Jukka; Hornberger, Lisa K; Sairanen, Heikki; Ojala, Tiina

2017-08-01

We investigated the impact of initial shunt type, a Blalock-Taussig (BT) shunt versus a right ventricle to pulmonary artery conduit (RV-PA) on myocardial function at different stages of surgical palliation in patients with hypoplastic left heart syndrome (HLHS). A population-based cohort of 63 Finnish children with HLHS (BT n  = 23, RV-PA n  = 40) born between 2003 and 2010 were studied retrospectively by echocardiography prior to Stages 1, 2 and 3 palliation and 0.5-3 years after Stage 3. For comparison of systolic myocardial function, we evaluated the RV fractional area change (FAC), strain, strain rate and mechanical synchrony from the apical 4-chamber view by velocity vector imaging. There were no intergroup differences in demographics during the study period. At baseline, no intergroup differences were detected in RV systolic myocardial function. Before Stage 2, RV FAC was higher ( P  = 0.03) in the RV-PA conduit group. At Stage 3, an increase in all systolic myocardial functional parameters was observed in the BT shunt group. After Stage 3, the BT shunt group had better RV systolic function. In multiple regression analysis, the shunt type and the stage of palliation had an impact on myocardial function. Although patients with HLHS initially palliated with a BT shunt demonstrate lower RV FAC after Stage I, RV FAC improves after Stage 2 with better systolic performance after Stage 3 compared with those initially palliated with an RV-PA conduit. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Effectiveness of dorsal metacarpal island flap for treating scar contracture of finger web].

PubMed

Qian, Jun; Rui, Yongjun; Zhang, Quanrong; Xue, Mingyu; Zhang, Zhihai

2011-11-01

To investigate the effectiveness of dorsal metacarpal island flap for treating scar contracture of the finger web. Between June 2009 and December 2010, 10 patients with scar contracture of the finger web were treated. There were 6 males and 4 females with an average age of 30 years (range, 14-57 years). Scar contracture was caused by injury in 8 cases, by burn in 1 case, and by operation in 1 case. The locations were the 1st web space in 1 case, the 2nd web space in 3 cases, the 3rd web space in 5 cases, and the 4th web space in 1 case. The disease duration was 3 to 9 months with an average of 5 months. The maximum abduction was 10-20 degrees. After web space scar release, the dorsal metacarpal island flap (3.5 cm x 1.2 cm-4.0 cm x 2.0 cm in size) was used to reconstruct web space (2.0 cm x 1.0 cm-3.0 cm x 1.8 cm in size). The donor site was directly sutured or repaired with local flaps. At 2 days after operation, necrosis occurred in 1 flap, which healed by extractive treatment. The other flaps survived and wound healed by first intention; all the flaps at donor sites survived and incision healed by first intention. Ten patients were followed up 6 to 15 months (mean, 9 months). The reconstructed web space had good appearance, the maximum abduction was 80 degrees in 1 case of the 1st web space scars contracture, and the maximum abduction was 35-45 degrees (mean, 40 degrees) in the other 9 cases. In 8 scar patients causing by injury, no scar contracture recurred during follow-up. It can achieve good results in appearance and function to use dorsal metacarpal island flap for treating scar contracture of the finger web.

Autologous fat graft as treatment of post short stature surgical correction scars.

PubMed

Maione, Luca; Memeo, Antonio; Pedretti, Leopoldo; Verdoni, Fabio; Lisa, Andrea; Bandi, Valeria; Giannasi, Silvia; Vinci, Valeriano; Mambretti, Andrea; Klinger, Marco

2014-12-01

Surgical limb lengthening is undertaken to correct pathological short stature. Among the possible complications related to this procedure, painful and retractile scars are a cause for both functional and cosmetic concern. Our team has already shown the efficacy of autologous fat grafting in the treatment of scars with varying aetiology, so we decided to apply this technique to scars related to surgical correction of dwarfism. A prospective study was conducted to evaluate the efficacy of autologous fat grafting in the treatment of post-surgical scars in patients with short-limb dwarfism using durometer measurements and a modified patient and observer scar assessment scale (POSAS), to which was added a parameter to evaluate movement impairment. Between January 2009 and September 2012, 36 children (28 female and 8 male) who presented retractile and painful post-surgical scars came to our unit and were treated with autologous fat grafting. Preoperative and postoperative mean durometer measurements were analysed using the analysis of variance (ANOVA) test and POSAS parameters were studied using the Wilcoxon rank sum test. There was a statistically significant reduction in all durometer measurements (p-value <0.05) and in all but one of the POSAS parameters (p-value <0.05) following treatment with autologous fat grafting. Surgical procedures to camouflage scars on lower limbs are not often used as a first approach and non-surgical treatments often lead to unsatisfactory results. In contrast, our autologous fat grafting technique in the treatment of post-surgical scars has been shown to be a valuable option in patients with short-limb dwarfism. There was a reduction of skin hardness and a clinical improvement of all POSAS parameters in all patients treated. Moreover, the newly introduced POSAS parameter appears to be reliable and we recommend that it is included to give a more complete evaluation of patient perception. Copyright © 2014 Elsevier Ltd. All rights reserved.

Unusual presentation of hidradenitis suppurativa with massive enlargement of penis.

PubMed

Baughman, Steven M; Cespedes, R Duane

2004-08-01

Hidradenitis suppurativa is a chronic, recurrent inflammatory disease affecting the cutaneous apocrine glands and resulting in their obstruction. This enigmatic disease causes recurrent episodes of infection, edema, scarring, and fibrosis of surrounding tissues. We present the case of a 55-year-old man with two decades of inguinal hidradenitis suppurativa that resulted in extensive penile subcutaneous lymphedema and enlargement secondary to scarring and obstructive lymphadenopathy. Reconstructive phalloplasty to restore normal penile function was required. Minimal recurrent induration, normal cutaneous sensation, and normal voiding and erectile function were noted at 3 years of follow-up.

Improving Functional and Aesthetic Outcomes in Syndromic Patients With Webbed Neck Deformity: Utilizing a Staged Endoscopic-Assisted Approach to Improve the Posterior Hairline and Decrease Scar Burden.

PubMed

Van Kouwenberg, Emily; Chattha, Anmol S; Adetayo, Oluwaseun A

2017-06-01

Webbed neck deformity (WND) can have significant functional and psychosocial impact on the developing child. Surgical correction can be challenging depending on the extent of the deformity, and patients often also have low posterior hairlines requiring simultaneous correction. Current surgical techniques include various methods of single-stage radical excision that often result in visible scar burden and residual deformity. There is currently no general consensus of which technique provides the best outcomes. A modified approach to WND was designed by the senior author aimed to decrease scar burden. Endoscopic-assisted fasciectomy was performed with simultaneous posterior hairline reconstruction with local tissue rearrangement camouflaged within the hair-bearing scalp. Staged surgical correction was planned rather than correction in a single operation. A retrospective review was performed to evaluate all patients who underwent this approach over a 2-year period. Two patients underwent the modified approach, a 17-year-old female with Noonan syndrome and a 2-year-old female with Turner syndrome. Both patients showed postoperative improvement in range of motion, contour of the jaw and neckline, and posterior hairline definition. Patients were found to have decreased scar burden compared with traditional techniques. A staged, combination approach of endoscopic-assisted fasciectomy and strategic local tissue reconstruction of the posterior hairline to correct WND achieves good functional and aesthetic results and good patient satisfaction. This modification should be considered when managing WND.

Protective effect of N-acetylcysteine activated carbon release microcapsule on myocardial ischemia-reperfusion injury in rats

PubMed Central

Cai, Zhaobin; Shi, Tingting; Zhuang, Rangxiao; Fang, Hongying; Jiang, Xiaojie; Shao, Yidan; Zhou, Hongping

2018-01-01

With the development of science and technology, and development of artery bypass, methods such as cardiopulmonary cerebral resuscitation have been practiced in recent years. Despite this, some methods fail to promote or recover the function of tissues and organs, and in some cases, may aggravate dysfunction and structural damage to tissues. The latter is typical of ischemia-reperfusion (IR) injury. Lipid peroxidation mediated by free radicals is an important process of myocardial IR injury. Myocardial IR has been demonstrated to induce the formation of large numbers of free radicals in rats, which promotes the peroxidation of lipids within unsaturated fatty acids in the myocardial cell membrane. Markers of lipid peroxidation include malondialdehyde, superoxide dismutase and lactic dehydrogenase. Recent studies have demonstrated that N-acetylcysteine (NAC) is able to dilate blood vessels, prevent oxidative damage, improve immunity, inhibit apoptosis and the inflammatory response and promote glutathione synthesis in cells. NAC also improves the systolic function of myocardial cells and cardiac function, prevents myocardial apoptosis, protects ventricular remodeling and vascular remodeling, reduces opiomelanocortin levels in the serum and increases the content of nitric oxide in the serum, thus improving vascular endothelial function. Therefore, NAC has potent pharmacological activity; however, the relatively fast metabolism of NAC, along with its large clinical dose and low bioavailability, limit its applications. The present study combined NAC with medicinal activated carbons, and prepared N-acetylcysteine activated carbon sustained-release microcapsules (ACNACs) to overcome the limitations of NAC. It was demonstrated that ACNACs exerted greater effective protective effects than NAC alone on myocardial IR injury in rats. PMID:29434769

Systemic pretreatment with dimethyloxalylglycine increases myocardial HIF-1α and VEGF production and improves functional recovery after acute ischemia/reperfusion.

PubMed

Poynter, Jeffrey A; Manukyan, Mariuxi C; Wang, Yue; Brewster, Benjamin D; Herrmann, Jeremy L; Weil, Brent R; Abarbanell, Aaron M; Meldrum, Daniel R

2011-08-01

Stem cells protect the heart from ischemic damage in part by the release of cytoprotective growth factors, particularly vascular endothelial growth factor (VEGF). Production of VEGF is regulated in part by levels of the transcription factor hypoxia inducible factor 1-α (HIF-1α). Dimethyloxalylglycine (DMOG) prevents the deactivation of HIF-1α and increases VEGF production. However, the effects of systemic DMOG treatment on myocardial tolerance for ischemia are unknown. We hypothesized that systemic pretreatment with DMOG would improve myocardial ischemic tolerance. To study this hypothesis, adult male rats were randomly given an intraperitoneal injection of DMOG (40 mg/kg in 1 mL saline, n = 5) or saline (1 mL, n = 6) 24 h before cardiectomy and isolated heart perfusion. All hearts were subjected to 15 min equilibration, 25 min ischemia and 40 min reperfusion. Myocardial function was continuously monitored. Following reperfusion, myocardial homogenates were analyzed for HIF-1α and VEGF production. We observed that hearts in the DMOG group exhibited greater recovery of left ventricular developed pressure LVDP, +dP/dt and -dP/dt. Myocardial HIF-1α and VEGF levels were increased by DMOG therapy. In conclusion, systemic pretreatment with DMOG augments post-ischemic myocardial functional recovery through increased HIF-1α levels and greater VEGF production. Copyright © 2011 Mosby, Inc. All rights reserved.

Experimental myocardial infarction

PubMed Central

Kumar, Raj; Joison, Julio; Gilmour, David P.; Molokhia, Farouk A.; Pegg, C. A. S.; Hood, William B.

1971-01-01

The hemodynamic effects of tachycardia induced by atrial pacing were investigated in left ventricular failure of acute and healing experimental myocardial infarction in 20 intact, conscious dogs. Myocardial infarction was produced by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 10-15 days prior to the study. 1 hr after acute myocardial infarction, atrial pacing at a rate of 180 beats/min decreased left ventricular end-diastolic pressure from 19 to 8 mm Hg and left atrial pressure from 17 to 12 mm Hg, without change in cardiac output. In the healing phase of myocardial infarction 1 wk later, atrial pacing decreased left ventricular end-diastolic pressure from 17 to 9 mm Hg and increased the cardiac output by 37%. This was accompanied by evidence of peripheral vasodilation. In two dogs with healing anterior wall myocardial infarction, left ventricular failure was enhanced by partial occlusion of the circumflex coronary artery. Both the dogs developed pulmonary edema. Pacing improved left ventricular performance and relieved pulmonary edema in both animals. In six animals propranolol was given after acute infarction, and left ventricular function deteriorated further. However the pacing-induced augmentation of cardiac function was unaltered and, hence, is not mediated by sympathetics. The results show that the spontaneous heart rate in left ventricular failure of experimental canine myocardial infarction may be less than optimal and that maximal cardiac function may be achieved at higher heart rates. Images PMID:4395910

Sequential evaluation of coronary flow patterns after primary angioplasty in acute anterior ST-elevation myocardial infarction predicts recovery of left ventricular systolic function.

PubMed

Sharif, Dawod; Sharif-Rasslan, Amal; Makhoul, Nabeel; Shefer, Arie; Hassan, Amin; Rosenschein, Uri

2014-05-01

Function of the microcirculation after primary percutaneous coronary intervention (PCI) is dynamic and contributes to unpredictability of recovery of left ventricular (LV) systolic function. This study was conducted to evaluate sequential Doppler velocity parameters of the left anterior descending coronary artery (LAD) in predicting recovery of global and regional LV systolic function. Thirty-five consecutive patients, 24 males, age 59 ± 12 years, with acute anterior ST-elevation myocardial infarction (STEMI) who had primary PCI were studied. Thrombolysis in myocardial infarction (TIMI) and myocardial blush grades were evaluated. Transthoracic echocardiographic (TTE) studies, evaluation of left ventricular ejection fraction (LVEF), LAD territory wall-motion score index (WMSI), and sampling of LAD Doppler velocities up to 6 hours post-PCI, 48 hours postprocedure, and predischarge were performed. Thrombolysis in myocardial infarction grade before PCI averaged 0.86 ± 1.19 and post-PCI 2.89 ± 0.32, P < 0.05. Myocardial blush grade before PCI was 0.41 ± 0.98 and after PCI 2.22 ± 0.93, P < 0.05. Diastolic velocity deceleration time (DDT) in the LAD early after PCI was less than 600 ms in 16 subjects. Immediately after PCI, in subjects with DDT > 600 ms, LVEF was 38.5 ± 6% and predischarge 49.2 ± 8.7%, P = 9.77 × 10−5 and LAD-WMSI decreased from 2 ± 0.38 to 1.4 ± 0.48, P = 0.000163. In subjects with DDT < 600 ms LAD-WMSI did not change significantly. Early and minimal LAD-DDT correlated with improvement in LV systolic function, r = 0.6, whereas post-PCI blush grade had lower correlation with LVEF, r = 0.39. Global and regional LV systolic function after PCI in acute anterior MI can be predicted by LAD-DDT better than by post-PCI myocardial blush.

Novel cardiovascular magnetic resonance oxygenation approaches in understanding pathophysiology of cardiac diseases.

PubMed

Sree Raman, Karthigesh; Nucifora, Gaetano; Selvanayagam, Joseph B

2018-05-01

Cardiovascular magnetic resonance imaging (CMR) permits accurate phenotyping of many cardiac diseases. CMR's inherent advantages are its non-invasive nature, lack of ionizing radiation and high accuracy and reproducibility. Furthermore, it is able to assess many aspects of cardiac anatomy, structure and function. Specifically, it can characterize myocardial tissue, myocardial function, myocardial mass, myocardial blood flow/perfusion, irreversible and reversible injury, all with a high degree of accuracy and reproducibility. Hence, CMR is a powerful tool in clinical and pre-clinical research. In recent years there have been novel advances in CMR myocardial tissue characterization. Oxygenation-sensitive CMR (OS-CMR) is a novel non-invasive, contrast independent technique that permits direct quantification of myocardial tissue oxygenation, both at rest and during stress. In this review, we will address the principles of the OS-CMR technique, its recent advances and summarize the studies in the effects of oxygenation on cardiac diseases. © 2018 John Wiley & Sons Australia, Ltd.

S100A8 and S100A9 Are Induced by Decreased Hydration in the Epidermis and Promote Fibroblast Activation and Fibrosis in the Dermis.

PubMed

Zhong, Aimei; Xu, Wei; Zhao, Jingling; Xie, Ping; Jia, Shengxian; Sun, Jiaming; Galiano, Robert D; Mustoe, Thomas A; Hong, Seok J

2016-01-01

The most critical function of the epidermis is to prevent water loss and maintain skin homeostasis. Disruption of the functional skin barrier causes delayed wound healing, hypertrophic scarring, and many skin diseases. Herein, we show that reduced hydration increases the expression of S100 protein family members, S100A8/S100A9, in stratified keratinocyte culture and human ex vivo skin culture. Immunohistological analyses show that S100A8/A9 are highly expressed in the epidermis of human hypertrophic scar and keloid tissues. Reduced hydration demonstrates activation of fibroblasts in the keratinocyte-fibroblast co-culture. In contrast, knockdown of S100A8 or S100A9 by RNA interference in keratinocytes failed to activate fibroblasts. Pretreatment with pharmacological blockers of S100A8/A9 receptors, Toll-like receptor 4 and receptor for advanced glycation end products, inhibits fibroblast activation induced by recombinant S100A8/A9 proteins. Moreover, we observe that local delivery of S100A8 protein results in a marked increase in hypertrophic scarring in the in vivo rabbit ear scar model. Our results indicate that hydration status promotes fibroblast activation and fibrosis by directly affecting the expression of inflammatory signaling in keratinocytes, thereby strongly suggesting S100A8/A9 to be novel targets in preventing scarring. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance.

PubMed

Metes-Kosik, Nicole; Luptak, Ivan; Dibello, Patricia M; Handy, Diane E; Tang, Shiow-Shih; Zhi, Hui; Qin, Fuzhong; Jacobsen, Donald W; Loscalzo, Joseph; Joseph, Jacob

2012-12-01

Selenium has complex effects in vivo on multiple homeostatic mechanisms such as redox balance, methylation balance, and epigenesis, via its interaction with the methionine-homocysteine cycle. In this study, we examined the hypothesis that selenium status would modulate both redox and methylation balance and thereby modulate myocardial structure and function. We examined the effects of selenium-deficient (<0.025 mg/kg), control (0.15 mg/kg), and selenium-supplemented (0.5 mg/kg) diets on myocardial histology, biochemistry and function in adult C57/BL6 mice. Selenium deficiency led to reactive myocardial fibrosis and systolic dysfunction accompanied by increased myocardial oxidant stress. Selenium supplementation significantly reduced methylation potential, DNA methyltransferase activity and DNA methylation. In mice fed the supplemented diet, inspite of lower oxidant stress, myocardial matrix gene expression was significantly altered resulting in reactive myocardial fibrosis and diastolic dysfunction in the absence of myocardial hypertrophy. Our results indicate that both selenium deficiency and modest selenium supplementation leads to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart. The crucial role selenium plays in maintaining the balance between redox and methylation pathways needs to be taken into account while optimizing selenium status for prevention and treatment of heart failure. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63-Integrin β1 Interaction.

PubMed

Takawale, Abhijit; Zhang, Pu; Patel, Vaibhav B; Wang, Xiuhua; Oudit, Gavin; Kassiri, Zamaneh

2017-06-01

Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis is a key feature of various cardiomyopathies and compromises cardiac systolic and diastolic performance. TIMP1 (tissue inhibitor of metalloproteinase-1) is consistently upregulated in myocardial fibrosis and is used as a marker of fibrosis. However, it remains to be determined whether TIMP1 promotes tissue fibrosis by inhibiting extracellular matrix degradation by matrix metalloproteinases or via an matrix metalloproteinase-independent pathway. We examined the function of TIMP1 in myocardial fibrosis using Timp1 -deficient mice and 2 in vivo models of myocardial fibrosis (angiotensin II infusion and cardiac pressure overload), in vitro analysis of adult cardiac fibroblasts, and fibrotic myocardium from patients with dilated cardiomyopathy (DCM). Timp1 deficiency significantly reduced myocardial fibrosis in both in vivo models of cardiomyopathy. We identified a novel mechanism for TIMP1 action whereby, independent from its matrix metalloproteinase-inhibitory function, it mediates an association between CD63 (cell surface receptor for TIMP1) and integrin β1 on cardiac fibroblasts, initiates activation and nuclear translocation of Smad2/3 and β-catenin, leading to de novo collagen synthesis. This mechanism was consistently observed in vivo, in cultured cardiac fibroblasts, and in human fibrotic myocardium. In addition, after long-term pressure overload, Timp1 deficiency persistently reduced myocardial fibrosis and ameliorated diastolic dysfunction. This study defines a novel matrix metalloproteinase-independent function of TIMP1 in promoting myocardial fibrosis. As such targeting TIMP1 could prove to be a valuable approach in developing antifibrosis therapies. © 2017 American Heart Association, Inc.

Psychological and psychosocial functioning of children with burn scarring using cosmetic camouflage: a multi-centre prospective randomised controlled trial.

PubMed

Maskell, Jessica; Newcombe, Peter; Martin, Graham; Kimble, Roy

2014-02-01

Burns leave patients with long-term physical scarring. Children with scarring are required to face challenges of reintegration into their community, including acceptance of an altered appearance and acceptance by others. This can be difficult given society's preoccupation with physical appearance. Limited research exists investigating validity of cosmetic camouflage as a psychosocial intervention for children with scarring. This study investigated whether using cosmetic camouflage (Microskin™) had a positive impact on health-related quality of life, self-concept and psychopathology for children and adolescents (8-17 years) with burn scarring. A prospective multi-centre randomised controlled trial was conducted across Australian and New Zealand paediatric hospitals. 63 participants (49 females, mean age 12.7 ± 2.1 years) were enrolled. Data points were baseline (Time 1) and at 8 weeks (Time 2) using reliable and valid psychometric measures. Findings indicate there were significant improvements in socialisation, school and appearance scales on the Paediatric Quality of Life Inventory and psychopathology scores particularly peer problems decreased. However self-concept remained stable from baseline throughout intervention use. Cosmetic camouflage appears to have a positive impact on quality of life particularly socialisation. Cosmetic camouflage is a valid tool to assist children with scarring to actively participate socially within their communities. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartmann, A.; Frenkel, J.; Hopf, R.

Amyloidosis is a systemic disease frequently involving the myocardium and leading to functional disturbances of the heart. Amyloidosis can mimic other cardiac diseases. A conclusive clinical diagnosis of cardiac involvement can only be made by a combination of different diagnostic methods. In 7 patients with myocardial amyloidosis we used a combined first-pass and static scintigraphy with technetium-99 m-pyrophosphate. There was only insignificant myocardial uptake of the tracer. The first-pass studies however revealed reduced systolic function in 4/7 patients and impaired diastolic function in 6/7 patients. Therefore, although cardiac amyloid could not be demonstrated in the static scintigraphy due to amyloidmore » fibril amount and composition, myocardial functional abnormalities were seen in the first-pass study.« less

Transmyocardial drilling revascularization combined with heparinized bFGF-incorporating stent activates resident cardiac stem cells via SDF-1/CXCR4 axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Guang-Wei; Wen, Ti; Gu, Tian-Xiang, E-mail: cmugtx@sina.com

Objective: To investigate whether transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) can promote myocardial regeneration after acute myocardial infarction (AMI). Methods: A model of AMI was generated by ligating the mid-third of left anterior descending artery (LAD) of miniswine. After 6 h, the animals were divided into none-treatment (control) group (n = 6) and TMDRSI group (n = 6). For TMDRSI group, two channels with 3.5 mm in diameter were established by a self-made drill in the AMI region, into which a stent was implanted. Expression of stromal cell-derived factor-1{sub {alpha}} (SDF-1{submore » {alpha}}) and CXC chemokine receptor 4 (CXCR4), cardiac stem cell (CSC)-mediated myocardial regeneration, myocardial apoptosis, myocardial viability, and cardiac function were assessed at various time-points. Results: Six weeks after the operation, CSCs were found to have differentiated into cardiomyocytes to repair the infarcted myocardium, and all above indices showed much improvement in the TMDRSI group compared with the control group (P < 0.001). Conclusions: The new method has shown to be capable of promoting CSCs proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following AMI and improving cardiac function. This may provide a new strategy for myocardial regeneration following AMI. -- Highlights: Black-Right-Pointing-Pointer The effects of TMDR and bFGF-stent on myocardial regeneration were studied in a pig model of AMI. Black-Right-Pointing-Pointer TMDR and bFGF-stent implantation activated CSCs via the SDF-1/CXCR4 axis. Black-Right-Pointing-Pointer CSC-mediated myocardial regeneration improved cardiac function. Black-Right-Pointing-Pointer It may be a new therapeutic strategy for AMI.« less

The real estate of myoblast cardiac transplantation: negative remodeling is associated with location.

PubMed

McCue, Jonathan D; Swingen, Cory; Feldberg, Tanya; Caron, Gabe; Kolb, Adam; Denucci, Christopher; Prabhu, Somnath; Motilall, Randy; Breviu, Brian; Taylor, Doris A

2008-01-01

Skeletal myoblast transplantation has been proposed as a therapy for ischemic cardiomyopathy owing to its possible role in myogenesis. The relative safety and efficacy based on location within scar is not known. We hypothesized that skeletal myoblasts transplanted into peripheral scar (compared with central scar) would more effectively attenuate negative left ventricular (LV) remodeling but at the risk of arrhythmia. New Zealand White rabbits (n = 34) underwent mid-left anterior descending artery (LAD) ligation to produce a transmural LV infarction. One month after LAD ligation, skeletal myoblasts were injected either in the scar center (n = 13) or scar periphery (n = 10) and compared with saline injection (n = 11). Holter monitoring and magnetic resonance imaging (MRI) was performed pre-injection; Holter monitoring was continued until 2 weeks after injection, with follow-up MRI at 1 month. The centrally treated animals demonstrated increased LV end-systolic volume, end-diastolic volume, and mass that correlated with the number of injected cells. There was a trend toward attenuation of negative LV remodeling in peripherally treated animals compared with vehicle. Significant late ectopy was seen in several centrally injected animals, with no late ectopy seen in peripherally injected animals. We noted untoward effects with respect to negative LV remodeling after central injection, suggesting that transplanted cell location with respect to scar may be a key factor in the safety and efficacy of skeletal myoblast cardiac transplantation. Administration of skeletal myoblasts into peripheral scar appears safe, with a trend toward improved function in comparison with sham injection.

Matrix Metalloproteinases Are Differentially Regulated and Responsive to Compression Therapy in a Red Duroc Model of Hypertrophic Scar.

PubMed

Travis, Taryn E; Ghassemi, Pejhman; Prindeze, Nicholas J; Moffatt, Lauren T; Carney, Bonnie C; Alkhalil, Abdulnaser; Ramella-Roman, Jessica C; Shupp, Jeffrey W

2018-01-01

Objective: Proteins of the matrix metalloproteinases family play a vital role in extracellular matrix maintenance and basic physiological processes in tissue homeostasis. The function and activities of matrix metalloproteinases in response to compression therapies have yet to be defined. Here, a swine model of hypertrophic scar was used to profile the transcription of all known 26 matrix metalloproteinases in scars treated with a precise compression dose. Methods: Full-thickness excisional wounds were created. Wounds underwent healing and scar formation. A subset of scars underwent 2 weeks of compression therapy. Biopsy specimens were preserved, and microarrays, reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry were performed to characterize the transcription and expression of various matrix metalloproteinase family members. Results: Microarray results showed that 13 of the known 26 matrix metalloproteinases were differentially transcribed in wounds relative to the preinjury skin. The predominant upregulation of these matrix metalloproteinases during early wound-healing stages declined gradually in later stages of wound healing. The use of compression therapy reduced this decline in 10 of the 13 differentially regulated matrix metalloproteinases. Further investigation of MMP7 using reverse transcription-polymerase chain reaction confirmed the effect of compression on transcript levels. Assessment of MMP7 at the protein level using Western blotting and immunohistochemistry was concordant. Conclusions: In a swine model of hypertrophic scar, the application of compression to hypertrophic scar attenuated a trend of decreasing levels of matrix metalloproteinases during the process of hypertrophic wound healing, including MMP7, whose enzyme regulation was confirmed at the protein level.

[Diagnosis and treatment of anxiety-depressive disorders in patients with myocardial infarction].

PubMed

Semiglazova, M V; Krasnov, V N; Dovzhenko, T V; Lebedev, A V

2012-01-01

The results of the study of psychopathological, somatic and functional characteristics of anxiety-depressive disorders in patients with acute myocardial infarction are presented. The authors confirmed the wide prevalence of these disorders in acute myocardial infarction and described the features of their diagnostics, dynamics and response to complex treatment. The impact of anxiety-depressive disorders on the clinical and functional state of the cardiovascular system and the dynamics of the patient's status due the concomitant anxiety-depressive disorder are considered.

Scaling of Myocardial Mass to Flow and Morphometry of Coronary Arteries

PubMed Central

Choy, Jenny Susana; Kassab, Ghassan S.

2009-01-01

There is no doubt that scaling relations exist between myocardial mass and morphometry of coronary vasculature. The purpose of this study is to quantify several morphological (diameter, length, and volume) and functional (flow) parameters of the coronary arterial tree in relation to myocardial mass. Eight normal porcine hearts of 117-244 g (mean of 177.5±32.7) were used in this study. Various coronary sub-trees of the Left Anterior Descending (LAD), Right Coronary (RCA) and Left Circumflex (LCX) arteries were perfused at pressure of 100 mmHg with different colors of a polymer (Microfil) in order to obtain rubber casts of arterial trees corresponding to different regions of myocardial mass. Volume, diameter and cumulative length of coronary arteries were reconstructed from casts to analyze their relationship to the perfused myocardial mass. Volumetric flow was measured in relationship with perfused myocardial mass. Our results show that arterial volume is linearly related to regional myocardial mass, whereas the sum of coronary arterial branch lengths, vessel diameters and volumetric flow show an approximately 3/4, 3/8 and 3/4 power-law relationship, respectively, in relation to myocardial mass. These scaling laws suggest fundamental design principles underlying the structure-function relationship of the coronary arterial tree that may facilitate diagnosis and management of diffuse coronary artery disease. PMID:18323461

Scaling of myocardial mass to flow and morphometry of coronary arteries.

PubMed

Choy, Jenny Susana; Kassab, Ghassan S

2008-05-01

There is no doubt that scaling relations exist between myocardial mass and morphometry of coronary vasculature. The purpose of this study is to quantify several morphological (diameter, length, and volume) and functional (flow) parameters of the coronary arterial tree in relation to myocardial mass. Eight normal porcine hearts of 117-244 g (mean of 177.5 +/- 32.7) were used in this study. Various coronary subtrees of the left anterior descending, right coronary, and left circumflex arteries were perfused at pressure of 100 mmHg with different colors of a polymer (Microfil) to obtain rubber casts of arterial trees corresponding to different regions of myocardial mass. Volume, diameter, and cumulative length of coronary arteries were reconstructed from casts to analyze their relationship to the perfused myocardial mass. Volumetric flow was measured in relationship with perfused myocardial mass. Our results show that arterial volume is linearly related to regional myocardial mass, whereas the sum of coronary arterial branch lengths, vessel diameters, and volumetric flow show an approximately 3/4, 3/8, and 3/4 power-law relationship, respectively, in relation to myocardial mass. These scaling laws suggest fundamental design principles underlying the structure-function relationship of the coronary arterial tree that may facilitate diagnosis and management of diffuse coronary artery disease.

Cardioprotective Properties of Aerobic and Resistance Training Against Myocardial Infarction.

PubMed

Barboza, C A; Souza, G I H; Oliveira, J C M F; Silva, L M; Mostarda, C T; Dourado, P M M; Oyama, L M; Lira, F S; Irigoyen, M C; Rodrigues, B

2016-06-01

We evaluated the effects of aerobic and resistance exercise training on ventricular morphometry and function, physical capacity, autonomic function, as well as on ventricular inflammatory status in trained rats prior to myocardial infarction. Male Wistar rats were divided into the following groups: sedentary+Sham, sedentary+myocardial infarction, aerobic trained+myocardial infarction, and resistance trained+myocardial infarction. Sham and myocardial infarction were performed after training periods. In the days following the surgeries, evaluations were performed. Aerobic training prevents aerobic (to a greater extent) and resistance capacity impairments, ventricular dysfunction, baroreflex sensitivity and autonomic disorders (vagal tonus decrease and sympathetic tonus increase) triggered by myocardial infarction. Resistance training was able to prevent negative changes to aerobic and resistance capacity (to a greater extent) but not to ventricular dysfunction, and it prevented cardiovascular sympathetic increments. Additionally, both types of training reduced left ventricle inflammatory cytokine concentration. Our results suggest that aerobic and, for the first time, dynamic resistance training were able to reduce sympathetic tonus to the heart and vessels, as well as preventing the increase in pro-inflammatory cytokine concentrations in the left ventricle of trained groups. These data emphasizes the positive effects of aerobic and dynamic resistance training on the prevention of the negative changes triggered by myocardial infarction. © Georg Thieme Verlag KG Stuttgart · New York.

Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-α improves acute myocardial function

PubMed Central

Herrmann, Jeremy L.; Abarbanell, Aaron M.; Weil, Brent R.; Wang, Yue; Poynter, Jeffrey A.; Manukyan, Mariuxi C.

2010-01-01

Stem cell-based therapies offer promising potential for myocardial infarction (MI), but endogenous molecules released in response to injury likely impair posttransplantation stem cell function. Stem cell-mediated cardioprotection occurs in part via paracrine effects, and transforming growth factor-α (TGF-α) has been shown to enhance paracrine function. However, it is unknown whether pretreating stem cells with TGF-α increases stem cell-mediated cardioprotection after acute MI. Mesenchymal stem cells (MSCs) were treated with TGF-α (250 ng/ml) for 24 h. Adult male Sprague-Dawley rat hearts were isolated and perfused using the Langendorff method. MI was induced by ligating the left anterior descending coronary artery. Postligation (30 min), vehicle or 1 × 106 MSCs with or without pretreatment were injected in the infarct border zones, and the hearts were perfused for an additional 60 min. Left ventricular function was continuously measured, and infarct size was assessed with Evans blue dye and 2,3,5-triphenyltetrazolium chloride staining. Myocardial production of interleukin (IL)-1β and IL-6 and caspase 3 activation was also measured. Left ventricular function decreased significantly following coronary artery ligation but improved following injection of untreated MSCs and to a greater extent after injection of pretreated MSCs. In addition, the infarct area, myocardial caspase 3 activation, and IL-6 production were lowest in hearts injected with pretreated cells. Intramyocardial injection of TGF-α-pretreated MSCs after acute MI is associated with increased myocardial function and decreased myocardial injury. This strategy may be useful for optimizing the therapeutic efficacy of stem cells for the treatment of acute MI. PMID:20484699

Novel use of a flowable collagen-glycosaminoglycan matrix (Integra™ Flowable Wound Matrix) combined with percutaneous cannula scar tissue release in treatment of post-burn malfunction of the hand--A preliminary 6 month follow-up.

PubMed

Hirche, C; Senghaas, A; Fischer, S; Hollenbeck, S T; Kremer, T; Kneser, U

2016-02-01

Long-term function following severe burns to the hand may be poor secondary to scar adhesions to the underlying tendons, webspaces, and joints. In this pilot study, we report the feasibility of applying a pasty dermal matrix combined with percutaneous cannula teno- and adhesiolysis. In this 6 month follow-up pilot study, we included eight hands in five patients with hand burns undergoing minimal-invasive, percutaneous cannula adhesiolysis and injection of INTEGRA™ Flowable Wound Matrix for a pilot study of this new concept. The flowable collagen-glycosaminoglycan wound matrix (FCGWM) was applied with a buttoned 2mm cannula to induce formation of a neo-gliding plane. Post treatment follow-up was performed to assess active range of motion (AROM), grip strength, Disabilities of the Arm, Shoulder and Hand (DASH) score, Vancouver Scar Scale (VSS) and quality of life Short-Form (SF)-36 questionnaire. No complications were detected associated with the treatment of FCGWM injection. The mean improvement (AROM) at 6 months was 30.6° for digits 2-5. The improvement in the DASH score was a mean of 9 points out of 100. The VSS improved by a mean of 2 points out of 14. The study demonstrates the feasibility and safety of percutaneous FCGWM for dermal augmentation after burn. Results from this pilot study show improvements in AROM for digits 2-5, functional scores from the patient's perspective (DASH) and scar quality (VSS). The flowable form of established INTEGRA™ wound matrix offers the advantage of minimal-invasive injection after scar release in the post-burned hand with a reduction in the risk of postsurgical re-scarring. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Magnetic Resonance Imaging as a Predictor of Survival Free of Life-Threatening Arrhythmias and Transplantation in Cardiac Sarcoidosis.

PubMed

Ekström, Kaj; Lehtonen, Jukka; Hänninen, Helena; Kandolin, Riina; Kivistö, Sari; Kupari, Markku

2016-05-02

Cardiac magnetic resonance imaging has a key role in today's diagnosis of cardiac sarcoidosis. We set out to investigate whether cardiac magnetic resonance imaging also helps predict outcome in cardiac sarcoidosis. Our work involved 59 patients with cardiac sarcoidosis (38 female, mean age 46±10 years) seen at our hospital since February 2004 and followed up after contrast-enhanced cardiac magnetic resonance imaging. The extent of myocardial late gadolinium enhancement (measured as percentage of left ventricular mass), the volumes and ejection fractions of the left and right ventricles, and the thickness of the basal interventricular septum were determined and analyzed for prognostic significance. By April 2015, 23 patients had reached the study's end point, consisting of a composite of cardiac death (n=3), cardiac transplantation (n=1), and occurrence of life-threatening ventricular tachyarrhythmias (n=19; ventricular fibrillation in 5 and sustained ventricular tachycardia in 14 patients). In univariate analysis, myocardial extent of late gadolinium enhancement predicted event-free survival, as did scar-like thinning (<4 mm) of the basal interventricular septum and the ejection fraction of the right ventricle (P<0.05 for all). In multivariate Cox regression analysis, extent of late gadolinium enhancement was the only independent predictor of outcome events on cardiac magnetic resonance imaging, with a hazard ratio of 2.22 per tertile (95% CI 1.07-4.59). An extent of late gadolinium enhancement >22% (third tertile) had positive and negative predictive values for serious cardiac events of 75% and 76%, respectively. Findings on cardiac magnetic resonance imaging and the extent of myocardial late gadolinium enhancement in particular help predict serious cardiac events in cardiac sarcoidosis. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Allogenic mesenchymal stem cell transplantation has a therapeutic effect in acute myocardial infarction in rats.

PubMed

Imanishi, Yukiko; Saito, Atsuhiro; Komoda, Hiroshi; Kitagawa-Sakakida, Satoru; Miyagawa, Shigeru; Kondoh, Haruhiko; Ichikawa, Hajime; Sawa, Yoshiki

2008-04-01

The goal of the study was to examine if allogenic mesenchymal stem cell (MSC) transplantation is a useful therapy for acute myocardial infarction (AMI). Buffer (control; group C, n=41), MSCs of male ACI rats (allogenic; group A, n=38, 5 x 10(6)), or MSCs of male LEW rats (syngenic; group S, n=40, 5 x 10(6)) were injected into the scar 15 min after myocardial infarction in female LEW rats. After 28 days, fractional left ventricular shortening significantly increased in groups A (21.3+/-1.7%, P=0.0467) and S (23.2+/-1.9%, P=0.0140), compared to group C (17.1+/-0.9%). Fibrosis in groups A and S was significantly lower. Quantitative PCR of the male-specific sry gene showed disappearance of donor cells within 28 days (5195+/-1975 cells). Secretion of vascular endothelial growth factor (VEGF) by MSCs was enhanced under hypoxic conditions in vitro. In groups A and S, the plasma VEGF concentration, VEGF level, and capillary density in recipient hearts increased after 28 days. Flow cytometry revealed the absence of B7 signal molecules on MSCs. A mixed lymphocyte reaction showed that ACI MSCs failed to stimulate proliferation of LEW lymphocytes. After 1 day after cell transplantation, transient increases in interleukin-1 beta and monocyte chemoattractant protein-1 in recipient hearts were enhanced in group A, with macrophage infiltration at the injection site. T cells remained at the level of normal tissue in all groups. We conclude that allogenic MSC transplantation therapy is useful for AMI. The donor MSCs disappear rapidly, but become a trigger of VEGF paracrine effect, without induction of immune rejection.

Experimental model of transthoracic, vascular-targeted, photodynamically induced myocardial infarction.

PubMed

Chrastina, Adrian; Pokreisz, Peter; Schnitzer, Jan E

2014-01-15

We describe a novel model of myocardial infarction (MI) in rats induced by percutaneous transthoracic low-energy laser-targeted photodynamic irradiation. The procedure does not require thoracotomy and represents a minimally invasive alternative to existing surgical models. Target cardiac area to be photodynamically irradiated was triangulated from the thoracic X-ray scans. The acute phase of MI was histopathologically characterized by the presence of extensive vascular occlusion, hemorrhage, loss of transversal striations, neutrophilic infiltration, and necrotic changes of cardiomyocytes. Consequently, damaged myocardium was replaced with fibrovascular and granulation tissue. The fibrotic scar in the infarcted area was detected by computer tomography imaging. Cardiac troponin I (cTnI), a specific marker of myocardial injury, was significantly elevated at 6 h (41 ± 6 ng/ml, n = 4, P < 0.05 vs. baseline) and returned to baseline after 72 h. Triphenyltetrazolium chloride staining revealed transmural anterolateral infarcts targeting 25 ± 3% of the left ventricle at day 1 with a decrease to 20 ± 3% at day 40 (n = 6 for each group, P < 0.01 vs. day 1). Electrocardiography (ECG) showed significant ST-segment elevation in the acute phase with subsequent development of a pathological Q wave and premature ventricular contractions in the chronic phase of MI. Vectorcardiogram analysis of spatiotemporal electrical signal transduction revealed changes in inscription direction, QRS loop morphology, and redistribution in quadrant areas. The photodynamically induced MI in n = 51 rats was associated with 12% total mortality. Histological findings, ECG abnormalities, and elevated cTnI levels confirmed the photosensitizer-dependent induction of MI after laser irradiation. This novel rodent model of MI might provide a platform to evaluate new diagnostic or therapeutic interventions.

Myocardial contusion in patients with blunt chest trauma as evaluated by thallium 201 myocardial scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bodin, L.; Rouby, J.J.; Viars, P.

1988-07-01

Fifty five patients suffering from blunt chest trauma were studied to assess the diagnosis of myocardial contusion using thallium 201 myocardial scintigraphy. Thirty-eight patients had consistent scintigraphic defects and were considered to have a myocardial contusion. All patients with scintigraphic defects had paroxysmal arrhythmias and/or ECG abnormalities. Of 38 patients, 32 had localized ST-T segment abnormalities; 29, ST-T segment abnormalities suggesting involvement of the same cardiac area as scintigraphic defects; 21, echocardiographic abnormalities. Sixteen patients had segmental hypokinesia involving the same cardiac area as the scintigraphic defects. Fifteen patients had clinical signs suggestive of myocardial contusion and scintigraphic defects. Almostmore » 70 percent of patients with blunt chest trauma had scintigraphic defects related to areas of myocardial contusion. When thallium 201 myocardial scintigraphy directly showed myocardial lesion, two-dimensional echocardiography and standard ECG detected related functional consequences of cardiac trauma.« less

Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring.

PubMed

Engrav, Loren H; Tuggle, Christopher K; Kerr, Kathleen F; Zhu, Kathy Q; Numhom, Surawej; Couture, Oliver P; Beyer, Richard P; Hocking, Anne M; Carrougher, Gretchen J; Ramos, Maria Luiza C; Klein, Matthew B; Gibran, Nicole S

2011-04-20

Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete. We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative)/Yorkshire(non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model. 1) The scars are still thick at forty-six weeks post wounding further validating the model. 2) The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.

Nanomaterials for Cardiac Myocyte Tissue Engineering.

PubMed

Amezcua, Rodolfo; Shirolkar, Ajay; Fraze, Carolyn; Stout, David A

2016-07-19

Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

[Effects of Chinese herbal compound for supplementing qi and activating blood circulation on actin, Cx43 expressions and gap junctional intercellular communication functions of myocardial cells in patients with Coxsackie virus B 3 viral myocarditis].

PubMed

Zhang, Ming-xue; He, Wei; Gu, Ping

2010-08-01

To observe the effect of Chinese herbal compound for supplementing qi and activating blood circulation (CHC) on the gap junctional intercellular communication (GJIC) function of myocardial cells in patients with Coxsackie virus B 3 (CVB3) viral myocarditis. Expressions of actin and connexin43 (Cx43) in myocardial cells of patients arranged in three groups (the normal control group, the viral infected group and the CHC treated group) were detected by immunohistochemical method; the fluorescence photobleaching recovery rate of cells was detected by laser scanning confocal microscope. As compared with the viral infected group, the expressions of actin and Cx43 were increased and the GJIC function was improved in the CHC treated group. CHC could antagonize viral injury on skeleton protein, and repair the structure of gap junction channel to improve the GJIC function of myocardial cells after being attacked by CVB3.

The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

PubMed

Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

2014-04-01

The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

Gualou Xiebai Decoction, a Traditional Chinese Medicine, Prevents Cardiac Reperfusion Injury of Hyperlipidemia Rat via Energy Modulation.

PubMed

Yan, Lu-Lu; Zhang, Wei-Yang; Wei, Xiao-Hong; Yan, Li; Pan, Chun-Shui; Yu, Yang; Fan, Jing-Yu; Liu, Yu-Ying; Zhou, Hua; Han, Jing-Yan; Yao, Xin-Sheng

2018-01-01

Background: Gualou Xiebai Decoction (GLXB) is a classic prescription of Chinese medicine used for the treatment of cardiac problems. The present study was designed to explore the effect and mechanism of GLXB on ischemia/reperfusion (I/R) induced disorders in myocardial structure and function, focusing on the regulation of energy metabolism and the RhoA/ROCK pathway. Methods: After hyperlipidemic rat model was established by oral administration of high fat diet, the rats were treated with GLXB for 6 weeks and subjected to 30 min occlusion of the left anterior descending coronary artery (LADCA) followed by 90 min reperfusion to elicit I/R challenge. Myocardial infarct size was assessed by Evans blue-TTC staining. Myocardial blood flow (MBF) and cardiac function were evaluated. Enzyme-linked immunosorbent assay was performed to examine the content of ATP, ADP, AMP, CK, CK-MB, LDH, cTnT, cTnI, and IL-6. Double staining of F-actin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was conducted to assess myocardial apoptosis. Expressions of ATP synthase subunit δ (ATP 5D), and RhoA and ROCK were determined by Western blotting. Results: Administration with GLXB at high dose for 6 weeks protected heart against I/R-induced MBF decrease, myocardial infarction and apoptosis, ameliorated I/R-caused impairment of cardiac function and myocardial structure, restored the decrease in the ratio of ADP/ATP and AMP/ATP, and the expression of ATP 5D with inhibiting the expression of RhoA and ROCK. Conclusions: Treatment with GLXB effectively protects myocardial structure and function from I/R challenge, possibly via regulating energy metabolism involving inactivation of RhoA/ROCK signaling pathway.

Cobalt Chloride Upregulates Impaired HIF-1α Expression to Restore Sevoflurane Post-conditioning-Dependent Myocardial Protection in Diabetic Rats.

PubMed

Wu, Jianjiang; Yang, Long; Xie, Peng; Yu, Jin; Yu, Tian; Wang, Haiying; Maimaitili, Yiliyaer; Wang, Jiang; Ma, Haiping; Yang, Yining; Zheng, Hong

2017-01-01

Previous studies from our group have demonstrated that sevoflurane post-conditioning (SPC) protects against myocardial ischemia reperfusion injury via elevating the intranuclear expression of hypoxia inducible factor-1 alpha (HIF-1α). However, diabetic SPC is associated with decreased myocardial protection and disruption of the HIF-1 signaling pathway. Previous studies have demonstrated that cobalt chloride (CoCl 2 ) can upregulate HIF-1α expression under diabetic conditions, but whether myocardial protection by SPC can be restored afterward remains unclear. We established a rat model of type 2 diabetes and a Langendorff isolated heart model of ischemia-reperfusion injury. Prior to reperfusion, 2.4% sevoflurane was used as a post-conditioning treatment. The diabetic rats were treated with CoCl 2 24 h before the experiment. At the end of reperfusion, tests were performed to assess myocardial function, infarct size, mitochondrial morphology, nitric oxide (NO), Mitochondrial reactive oxygen species (ROS), mitochondrial respiratory function and enzyme activity, HIF-1α, vascular endothelial growth factor (VEGF) and endothelial NO synthase (eNOS) protein levels. In addition, myocardial protection by SPC was monitored after the blood glucose levels were lowered by insulin. The diabetic state was associated with deficient SPC protection and decreased HIF-1α expression. After treating the diabetic rats with CoCl 2 , SPC significantly upregulated the expression of HIF-1α, VEGF and eNOS, which markedly improved cardiac function, NO, mitochondrial respiratory function, and enzyme activity and decreased the infarction areas and ROS. In addition, these effects were not influenced by blood glucose levels. This study proved that CoCl 2 activates the HIF-1α signaling pathway, which restores SPC-dependent myocardial protection under diabetic conditions, and the protective effects of SPC were independent of blood glucose levels.

Actinic cheilitis: aesthetic and functional comparative evaluation of vermilionectomy using the classic and W-plasty techniques.

PubMed

Rossoe, Ed Wilson Tsuneo; Tebcherani, Antonio José; Sittart, José Alexandre; Pires, Mario Cezar

2011-01-01

Chronic actinic cheilitis is actinic keratosis located on the vermilion border. Treatment is essential because of the potential for malignant transformation. To evaluate the aesthetic and functional results of vermilionectomy using the classic and W-plasty techniques in actinic cheilitis. In the classic technique, the scar is linear and in the W-plasty one, it is a broken line. 32 patients with clinical and histopathological diagnosis of actinic cheilitis were treated. Out of the 32 patients, 15 underwent the W-plasty technique and 17 underwent the classic one. We evaluated parameters such as scar retraction and functional changes. A statistically significant association between the technique used and scar retraction was found, which was positive when using the classic technique (p = 0.01 with Yates' correction). The odds ratio was calculated at 11.25, i.e., there was a greater chance of retraction in patients undergoing the classic technique. Both techniques revealed no functional changes. We evaluated postoperative complications such as the presence of crusts, dry lips, paresthesia, and suture dehiscence. There was no statistically significant association between complications and the technique used (p = 0.69). We concluded that vermilionectomy using the W-plasty technique shows better cosmetic results and similar complication rates.

Surgical Management of Large Periorbital Cutaneous Defects: Aesthetic Considerations and Technique Refinements.

PubMed

Zou, Yun; Hu, Li; Tremp, Mathias; Jin, Yunbo; Chen, Hui; Ma, Gang; Lin, Xiaoxi

2018-02-23

The aim of this study was to repair large periorbital cutaneous defects by an innovative technique called PEPSI (periorbital elevation and positioning with secret incisions) technique with functional and aesthetic outcomes. In this retrospective study, unilateral periorbital cutaneous defects in 15 patients were repaired by the PEPSI technique. The ages of patients ranged from 3 to 46 years (average, 19 years). The outcome evaluations included scars (Vancouver Scar Scale and visual analog scale score), function and aesthetic appearance of eyelids, and patient satisfaction. The repair size was measured by the maximum advancement distance of skin flap during operation. All patients achieved an effective repair with a mean follow-up of 18.3 months. Except one with a small (approximately 0.3 cm) necrosis, all patients healed with no complication. The mean Vancouver Scar Scale and visual analog scale scores were 2.1 ± 1.7 and 8.5 ± 1.2, respectively. Ideal cosmetic and functional outcomes were achieved in 14 patients (93.3%). All patients achieved complete satisfaction except 1 patient with partial satisfaction. The mean maximum advancement distance of skin flap was 20.2 mm (range, 8-50 mm). This study demonstrated that the PEPSI technique is an effective method to repair large periorbital cutaneous defects with acceptable functional and aesthetic outcomes.

[Rehabilitation of burn victims. A difficult path back to normality].

PubMed

Butz, M; Conrady, D; Baumgärtler, H; Mentzel, H E

2002-06-13

The most important aims of rehabilitation in burn victims is the restitution and improvement of joint mobility, mimicry and pulmonary function, as well as of muscular endurance and strength. In addition to the management of scars, therefore, patient instruction in unsupervised training and scar care, as well as promotion of re-integration into day-to-day life are essential. Depending on the parts of the body affected, measures may include manual therapy, active exercise, treatment with ultrasound, proprioceptive neuromuscular facilitation in the case of facial burns, respiratory therapy and ergotherapy and, finally coordination training. Treatment of the scars themselves requires a combination of a number of measures, all of which should be of an "active" nature. Of proven value are manual massage of scar tissue, stretching exercises, the use of silicone, special splints and compression clothing, as well as laser therapy. Rehabilitation measures should be applied for not less than 4 weeks. Where indicated, further surgical measures should be discussed with the patient.

Effect of Bone Marrow-Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction: Twelve Months CMR and Long-Term Clinical Results.

PubMed

Sürder, Daniel; Manka, Robert; Moccetti, Tiziano; Lo Cicero, Viviana; Emmert, Maximilian Y; Klersy, Catherine; Soncin, Sabrina; Turchetto, Lucia; Radrizzani, Marina; Zuber, Michel; Windecker, Stephan; Moschovitis, Aris; Bühler, Ines; Kozerke, Sebastian; Erne, Paul; Lüscher, Thomas F; Corti, Roberto

2016-07-22

Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). To demonstrate long-term efficacy of BM-MNC treatment after AMI. In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9±9.8% for control (mean±SD), -0.9±10.5% for the early treatment group, and -0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186. © 2016 American Heart Association, Inc.

Coronary flow velocity reserve by echocardiography: feasibility, reproducibility and agreement with PET in overweight and obese patients with stable and revascularized coronary artery disease.

PubMed

Olsen, Rasmus Huan; Pedersen, Lene Rørholm; Snoer, Martin; Christensen, Thomas Emil; Ghotbi, Adam Ali; Hasbak, Philip; Kjaer, Andreas; Haugaard, Steen B; Prescott, Eva

2016-06-07

Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography of the LAD is used to assess microvascular function but validation studies in clinical settings are lacking. We aimed to assess feasibility, reproducibility and agreement with myocardial flow reserve (MFR) measured by PET in overweight and obese patients. Participants with revascularized coronary artery disease were examined by CFVR. Subgroups were examined by repeated CFVR (reproducibility) or Rubidium-82-PET (agreement). To account for time variation, results were computed for scans performed within a week (1-week) and for all scans regardless of time gap (total) and to account for scar tissue for patients with and without previous myocardial infarction (MI). Eighty-six patients with median BMI 30.9 (IQR 29.4-32.9) kg × m(-2) and CFVR 2.29 (1.90-2.63) were included. CFVR was feasible in 83 (97 %) using a contrast agent in 14 %. For reproducibility overall (n = 21) limits of agreement (LOA) were (-0.75;0.71), within-subjects coefficient of variation (CV) 11 %, and reliability 0.84. For reproducibility within 1-week (n = 13) LOA were (-0.33;0.25), within-subjects CV 5 %, and reliability 0.97. Agreement with MFR of the LAD territory (n = 35) was without significant bias and overall LOA were (-1.40;1.46). Agreement was best for examinations performed within 1-week of participants without MI of the LAD-territory (n = 12); LOA = (-0.68;0.88). CFVR was highly feasible with a good reproducibility on par with other contemporary measures applied in cardiology. Agreement with MFR was acceptable, though discrepancy related to prior MI has to be considered. CFVR of LAD is a valid tool in overweight and obese patients.

VALSARTAN REGULATES MYOCARDIAL AUTOPHAGY AND MITOCHONDRIAL TURNOVER IN EXPERIMENTAL HYPERTENSION

PubMed Central

Zhang, Xin; Li, Zi-Lun; Crane, John A.; Jordan, Kyra L.; Pawar, Aditya S.; Textor, Stephen C.; Lerman, Amir; Lerman, Lilach O.

2014-01-01

Renovascular hypertension alters cardiac structure and function. Autophagy is activated during left ventricular hypertrophy and linked to adverse cardiac function. The Angiotensin II receptor blocker Valsartan lowers blood pressure and is cardioprotective, but whether it modulates autophagy in the myocardium is unclear. We hypothesized that Valsartan would alleviate autophagy and improve left ventricular myocardial mitochondrial turnover in swine renovascular hypertension. Domestic pigs were randomized to control, unilateral renovascular hypertension, and renovascular hypertension treated with Valsartan (320 mg/day) or conventional triple therapy (Reserpine+hydralazine+hydrochlorothiazide) for 4 weeks post 6-weeks of renovascular hypertension (n=7 each group). Left ventricular remodeling, function and myocardial oxygenation and microcirculation were assessed by multi-detector computer tomography, blood-oxygen-level-dependent magnetic resonance imaging and microcomputer tomography. Myocardial autophagy, markers for mitochondrial degradation and biogenesis, and mitochondrial respiratory-chain proteins were examined ex vivo. Renovascular hypertension induced left ventricular hypertrophy and myocardial hypoxia, enhanced cellular autophagy and mitochondrial degradation, and suppressed mitochondrial biogenesis. Valsartan and triple therapy similarly decreased blood pressure, but Valsartan solely alleviated left ventricular hypertrophy, ameliorated myocardial autophagy and mitophagy, and increased mitochondrial biogenesis. In contrast, triple therapy only slightly attenuated autophagy and preserved mitochondrial proteins, but elicited no improvement in mitophagy. These data suggest a novel potential role of Valsartan in modulating myocardial autophagy and mitochondrial turnover in renovascular hypertension-induced hypertensive heart disease, which may possibly bolster cardiac repair via a blood pressure-independent manner. PMID:24752430

Cost evaluation of cardiovascular magnetic resonance versus coronary angiography for the diagnostic work-up of coronary artery disease: application of the European Cardiovascular Magnetic Resonance registry data to the German, United Kingdom, Swiss, and United States health care systems.

PubMed

Moschetti, Karine; Muzzarelli, Stefano; Pinget, Christophe; Wagner, Anja; Pilz, Günther; Wasserfallen, Jean-Blaise; Schulz-Menger, Jeanette; Nothnagel, Detle; Dill, Torsten; Frank, Herbert; Lombardi, Massimo; Bruder, Oliver; Mahrholdt, Heiko; Schwitter, Jürg

2012-06-14

Cardiovascular magnetic resonance (CMR) has favorable characteristics for diagnostic evaluation and risk stratification of patients with known or suspected CAD. CMR utilization in CAD detection is growing fast. However, data on its cost-effectiveness are scarce. The goal of this study is to compare the costs of two strategies for detection of significant coronary artery stenoses in patients with suspected coronary artery disease (CAD): 1) Performing CMR first to assess myocardial ischemia and/or infarct scar before referring positive patients (defined as presence of ischemia and/or infarct scar to coronary angiography (CXA) versus 2) a hypothetical CXA performed in all patients as a single test to detect CAD. A subgroup of the European CMR pilot registry was used including 2,717 consecutive patients who underwent stress-CMR. From these patients, 21% were positive for CAD (ischemia and/or infarct scar), 73% negative, and 6% uncertain and underwent additional testing. The diagnostic costs were evaluated using invoicing costs of each test performed. Costs analysis was performed from a health care payer perspective in German, United Kingdom, Swiss, and United States health care settings. In the public sectors of the German, United Kingdom, and Swiss health care systems, cost savings from the CMR-driven strategy were 50%, 25% and 23%, respectively, versus outpatient CXA. If CXA was carried out as an inpatient procedure, cost savings were 46%, 50% and 48%, respectively. In the United States context, cost savings were 51% when compared with inpatient CXA, but higher for CMR by 8% versus outpatient CXA. This analysis suggests that from an economic perspective, the use of CMR should be encouraged as a management option for patients with suspected CAD.

Isthmus sites identified by Ripple Mapping are usually anatomically stable: A novel method to guide atrial substrate ablation?

PubMed

Luther, Vishal; Qureshi, Norman; Lim, Phang Boon; Koa-Wing, Michael; Jamil-Copley, Shahnaz; Ng, Fu Siong; Whinnett, Zachary; Davies, D Wyn; Peters, Nicholas S; Kanagaratnam, Prapa; Linton, Nick

2018-03-01

Postablation reentrant ATs depend upon conducting isthmuses bordered by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the voltage amplitude of an electrogram depends upon the myocardial activation sequence. Furthermore, a voltage threshold that defines atrial scar is unknown. We used Ripple Mapping (RM) to test whether these isthmuses were anatomically fixed between different activation vectors and atrial rates. We studied post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used with CARTO Confidense for high-density mapping. RM visualized the pattern of activation, and the voltage threshold below which no activation was seen. Isthmuses were characterized at this threshold between maps for each patient. Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced 2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 ± 30 ms). Point density was similar between maps (Map 1: 2,589 ± 1,330; Map 2: 2,214 ± 1,384; P  =  0.31). RM activation threshold was 0.16 ± 0.08 mV. Thirty-one isthmuses were identified in Map 1 (median 3 per map; width 27 ± 15 mm; 7 anterior; 6 roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were unexpectedly identified within regions without prior ablation. AT1 was treated following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of 16 isthmuses (88%) were consistent between the two maps (four were inadequately mapped). Wavefront collision caused variation in low voltage distribution in 2 of 16 (12%). The distribution of isthmuses and nonconducting tissue within the ablated left atrium, as defined by RM, appear concordant between rhythms. This could guide a substrate ablative approach. © 2018 Wiley Periodicals, Inc.

Myocardial aging as a T-cell–mediated phenomenon

PubMed Central

Ramos, Gustavo Campos; van den Berg, Anne; Nunes-Silva, Vânia; Weirather, Johannes; Peters, Laura; Burkard, Matthias; Friedrich, Mike; Pinnecker, Jürgen; Abeßer, Marco; Heinze, Katrin G.; Schuh, Kai; Beyersdorf, Niklas; Kerkau, Thomas; Demengeot, Jocelyne; Frantz, Stefan; Hofmann, Ulrich

2017-01-01

In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissue-resident leukocytes and with an accumulation of activated CD4+ Foxp3− (forkhead box P3) IFN-γ+ T cells in the heart-draining lymph nodes. A comprehensive characterization of different aged immune-deficient mouse strains revealed that T cells significantly contribute to age-related myocardial inflammation and functional decline. Upon adoptive cell transfer, the T cells isolated from the mediastinal lymph node (med-LN) of aged animals exhibited increased cardiotropism, compared with cells purified from young donors or from other irrelevant sites. Nevertheless, these cells caused rather mild effects on cardiac functionality, indicating that myocardial aging might stem from a combination of intrinsic and extrinsic (immunological) factors. Taken together, the data herein presented indicate that heart-directed immune responses may spontaneously arise in the elderly, even in the absence of a clear tissue damage or concomitant infection. These observations might shed new light on the emerging role of T cells in myocardial diseases, which primarily affect the elderly population. PMID:28255084

Calpain inhibition preserves myocardial structure and function following myocardial infarction.

PubMed

Mani, Santhosh K; Balasubramanian, Sundaravadivel; Zavadzkas, Juozas A; Jeffords, Laura B; Rivers, William T; Zile, Michael R; Mukherjee, Rupak; Spinale, Francis G; Kuppuswamy, Dhandapani

2009-11-01

Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca(2+)-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated (n = 6) and untreated (n = 6) MI mice were used to study changes in myocardial structure and function after 4 days of MI, where end-diastolic volume (EDV) and left ventricular ejection fraction (EF) were measured by echocardiography. Calpain activation and programmed cell death were measured by immunohistochemistry, Western blotting, and TdT-mediated dUTP nick-end labeling (TUNEL). In MI mice, calpeptin treatment resulted in a significant improvement in EF [EF decreased from 67 + or - 2% pre-MI to 30 + or - 4% with MI only vs. 41 + or - 2% with MI + calpeptin] and attenuated the increase in EDV [EDV increased from 42 + or - 2 microl pre-MI to 73 + or - 4 microl with MI only vs. 55 + or - 4 microl with MI + calpeptin]. Furthermore, calpeptin treatment resulted in marked reduction in calpain- and caspase-3-associated changes and TUNEL staining. These studies indicate that calpain contributes to MI-induced alterations in myocardial structure and function and that it could be a potential therapeutic target in treating MI patients.

Myocardial oedema in acute myocarditis detected by echocardiographic 2D myocardial deformation analysis.

PubMed

Løgstrup, B B; Nielsen, J M; Kim, W Y; Poulsen, S H

2016-09-01

The clinical diagnosis of acute myocarditis is based on symptoms, electrocardiography, elevated myocardial necrosis biomarkers, and echocardiography. Often, conventional echocardiography reveals no obvious changes in global cardiac function and therefore has limited diagnostic value. Myocardial deformation imaging by echocardiography is an evolving method used to characterize quantitatively longitudinal systolic function, which may be affected in acute myocarditis. The aim of our study was to assess the utility of echocardiographic deformation imaging of the left ventricle in patients with diagnosed acute myocarditis in whom cardiovascular magnetic resonance (CMR) evaluation was performed. We included 28 consecutive patients (mean age 32 ± 13 years) with CMR-verified diagnosis of acute myocarditis according to the Lake Louise criteria. Cardiac function was evaluated by a comprehensive assessment of left ventricular (LV) function, including 2D speckle-tracking echocardiography. We found no significant correlation between the peak values of cardiac enzymes and the amount of myocardial oedema assessed by CMR (troponin: r= 0.3; P = 0.05 and CK-MB: r = 0.1; P = 0.3). We found a larger amount of myocardial oedema in the basal part of the left ventricle [American Heart Association (AHA) segments 1-6] in inferolateral and inferior segments, compared with the anterior, anterolateral, anteroseptal, and inferoseptal segments. In the mid LV segments (AHA segments 7-12), this was more pronounced in the anterior, anterolateral, and inferolateral segments. Among conventional echocardiographic parameters, LV function was not found to correlate with the amount of myocardial oedema of the left ventricle. In contrast, we found the wall motion score index to be significantly correlated with the amount of myocardial oedema, but this correlation was only present in patients with an extensive amount of oedema (>11% of the total left ventricle). Global longitudinal systolic myocardial strain correlated significantly with the amount of oedema (r = 0.65; P < 0.001). We found that both the epicardial longitudinal and the endocardial longitudinal systolic strains were significantly correlated with oedema (r = 0.55; P = 0.003 and r = 0.54; P < 0.001). In patients with acute myocarditis, 2D speckle-tracking echocardiography was a useful tool in the diagnostic process of acute myocarditis. Global longitudinal strain adds important information that can support clinical and conventional echocardiographic evaluation, especially in patients with preserved LV ejection fraction in relation to the diagnosis and degree of myocardial dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Functional Cardiac Magnetic Resonance Imaging (MRI) in the Assessment of Myocardial Viability and Perfusion

PubMed Central

2003-01-01

Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness safety and cost-effectiveness of using functional cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability and perfusion in patients with coronary artery disease and left ventricular dysfunction. Results Functional MRI has become increasingly investigated as a noninvasive method for assessing myocardial viability and perfusion. Most patients in the published literature have mild to moderate impaired LV function. It is possible that the severity of LV dysfunction may be an important factor that can alter the diagnostic accuracy of imaging techniques. There is some evidence of comparable or better performance of functional cardiac MRI for the assessment of myocardial viability and perfusion compared with other imaging techniques. However limitations to most of the studies included: Functional cardiac MRI studies that assess myocardial viability and perfusion have had small sample sizes. Some studies assessed myocardial viability/perfusion in patients who had already undergone revascularization, or excluded patients with a prior MI (Schwitter et al., 2001). Lack of explicit detail of patient recruitment. Patients with LVEF >35%. Interstudy variability in post MI imaging time(including acute or chronic MI), when patients with a prior MI were included. Poor interobserver agreement (kappa statistic) in the interpretation of the results. Traditionally, 0.80 is considered “good”. Cardiac MRI measurement of myocardial perfusion to as an adjunct tool to help diagnose CAD (prior to a definitive coronary angiography) has also been examined in some studies, with methodological limitations, yielding comparable results. Many studies examining myocardial viability and perfusion report on the accuracy of imaging methods with limited data on long-term patient outcome and management. Kim et al. (2000) revealed that the transmural extent of hyperenhancement was significantly related to the likelihood of improvement in contractility after revascularization. However, the LVEF in the patient population was 43% prior to revascularization. It is important to know whether the technique has the same degree of accuracy in patients who have more severe LV dysfunction and who would most benefit from an assessment of myocardial viability. “Substantial” viability used as a measure of a patient’s ability to recover after revascularization has not been definitively reported (how much viability is enough?). Patients with severe LV dysfunction are more likely to have mixtures of surviving myocardium, including normal, infarcted, stunned and hibernating myocardium (Cowley et al., 1999). This may lead to a lack of homogeneity of response to testing and to revascularization and contribute to inter- and intra-study differences. There is a need for a large prospective study with adequate follow-up time for patients with CAD and LV dysfunction (LVEF<35%) comparing MRI and an alternate imaging technique. There is some evidence that MRI has comparable sensitivity, specificity and accuracy to PET for determining myocardial viability. However, there is a lack of evidence comparing the accuracy of these two techniques to predict LV function recovery. In addition, some studies refer to PET as the gold standard for the assessment of myocardial viability. Therefore, PET may be an ideal noninvasive imaging comparator to MRI for a prospective study with follow-up. To date, there is a lack of cost-effectiveness analyses (or any economic analyses) of functional cardiac MRI versus an alternate noninvasive imaging method for the assessment of myocardial viability/perfusion. Conclusion There is some evidence that the accuracy of functional cardiac MRI compares favourably with alternate imaging techniques for the assessment of myocardial viability and perfusion. There is insufficient evidence whether functional cardiac MRI can better select which patients [who have CAD and severe LV dysfunction (LVEF <35%)] may benefit from revascularization compared with an alternate noninvasive imaging technology. There is insufficient evidence whether functional cardiac MRI can better select which patients should proceed to invasive coronary angiography for the definitive diagnosis of CAD, compared with an alternate noninvasive imaging technology. There is a need for a large prospective (potentially multicentre) study with adequate follow-up time for patients with CAD and LV dysfunction (LVEF<35%) comparing MRI and PET. Since longer follow-up time may be associated with restenosis or graft occlusion, it has been suggested to have serial measurements after revascularization (Cowley et al., 1999). PMID:23074446

Cpg-ODN, a TLR9 Agonist, Aggravates Myocardial Ischemia/Reperfusion Injury by Activation of TLR9-P38 MAPK Signaling.

PubMed

Xie, Liang; He, Songqing; Kong, Na; Zhu, Ying; Tang, Yi; Li, Jianhua; Liu, Zhengbing; Liu, Jing; Gong, Jianbin

2018-06-19

Toll-like receptors (TLRs) have been implicated in myocardial ischemia/ reperfusion (I/R) injury. We examined the effect of CpG-oligodeoxynucleotide (ODN) on myocardial I/R injury. Male Sprague-Dawley rats were treated with either CpG-ODN or control ODN 1 h prior to myocardial ischemia (30 min) followed by reperfusion. Rats treated with phosphate-buffered saline (PBS) served as I/R controls (n = 8/group). Infarct size was determined by 2,3,5-triphenyltetrazolium chloride and Evans blue straining. Cardiac function was examined by echocardiography before and up to 14 days after myocardial I/R. CpG-ODN administration significantly increased infarct size and reduced cardiac function and survival rate after myocardial I/R, compared to the PBS-treated I/R group. Control-ODN did not alter I/R-induced myocardial infarct size, cardiac dysfunction, and survival rate. Additionally, CpG-ODN promoted I/R-induced myocardial apoptosis and cleaved caspase-3 levels in the myocardium. CpG-ODN increased TLR9 activation and p38 phosphorylation in the myocardium. In vitro data also suggested that CpG-ODN treatment induced TLR9 activation and p38 phosphorylation. Importantly, p38 mitogen-activated protein kinase (MAPK) inhibition abolished CpG-ODN-induced cardiac injury. CpG-ODN, the TLR9 ligand, accelerates myocardial I/R injury. The mechanisms involve activation of the TLR9-p38 MAPK signaling pathway. © 2018 The Author(s). Published by S. Karger AG, Basel.

Adenosine triphosphate postconditioning is associated with better preserved global and regional cardiac function during myocardial ischemia and reperfusion: a speckle tracking imaging-based echocardiologic study.

PubMed

Ren, Min; Liu, Yujie; Zhao, Huiya; Dong, Shixia; Jiang, Zhonghui; Li, Keting; Tian, Jiawei

2016-10-01

Effects of ischemic postconditioning (IPostC) and adenosine triphosphate (ATP)-mediated pharmacologic postconditioning (ATP-PPostC) on cardiac function were evaluated by speckle tracking imaging (STI)-based echocardiography. A myocardial I/R model was induced in rabbits by reversible ligation of the left ventricular branch of coronary artery. Rabbits were randomized into three groups: ischemia and reperfusion (IR) (no further intervention), IPostC, and ATP-PPostC groups. Cardiac function was evaluated by conventional and STI-based echocardiography. Myocardial necrosis, apoptosis, and myocardial mRNAs of apoptosis-related proteins (Bcl-2 and Bax) were evaluated. Speckle tracking imaging (STI)-based echocardiography revealed that IPostC and ATP-PPostC were associated with better preserved global and regional cardiac function, as indicated by significantly increased GLSrsys, GLSrd, GLSsys, SrLsys, SrLd, and SLsys in both groups (all P<.5). Subsequent pathologic studies indicate that the percentage of necrotic myocardium and permillage of apoptotic cells were significantly lower in the IPostC and ATP-PPostC groups than in the IR group (all P<.05). Moreover, both IPostC and ATP-PPostC were associated with increased Bcl-2 mRNA levels and reduced Bax mRNA levels. IPostC and ATP-PPostC may exert cardioprotective functions by better preservation of cardiac function during the I/R process and at least partly via attenuation of myocardial apoptosis. © 2016 John Wiley & Sons Ltd.

Myocardial regeneration potential of adipose tissue-derived stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Xiaowen, E-mail: baixw01@yahoo.com; Alt, Eckhard, E-mail: ealt@mdanderson.org

Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derivedmore » stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying mechanisms for beneficial effect on cardiac function, and safety issues.« less

Erythropoietin alleviates post-resuscitation myocardial dysfunction in rats potentially through increasing the expression of angiotensin II receptor type 2 in myocardial tissues

PubMed Central

Zhou, Hourong; Huang, Jia; Zhu, Li; Cao, Yu

2018-01-01

Activation of renin-angiotensin system (RAS) is one of the pathological mechanisms associated with myocardial ischemia-reperfusion injury following resuscitation. The present study aimed to determine whether erythropoietin (EPO) improves post-resuscitation myocardial dysfunction and how it affects the renin-angiotensin system. Sprague-Dawley rats were randomly divided into sham, vehicle, epinephrine (EP), EPO and EP + EPO groups. Excluding the sham group, all groups underwent cardiopulmonary resuscitation (CPR) 4 min after asphyxia-induced cardiac arrest (CA). EP and/or EPO was administrated by intravenous injection when CPR began. The results demonstrated that the vehicle group exhibited lower mean arterial pressure, left ventricular systolic pressure, maximal ascending rate of left ventricular pressure during left ventricular isovolumic contraction and maximal descending rate of left ventricular pressure during left ventricular isovolumic relaxation (+LVdP/dt max and -LVdP/dt max, respectively), and higher left ventricular end-diastolic pressure, compared with the sham group following return of spontaneous circulation (ROSC). Few significant differences were observed concerning the myocardial function between the vehicle and EP groups; however, compared with the vehicle group, EPO reversed myocardial function indices following ROSC, excluding-LVdP/dt max. Serum renin and angiotensin (Ang) II levels were measured by ELISA. The serum levels of renin and Ang II were significantly increased in the vehicle group compared with the sham group, which was also observed for the myocardial expression of renin and Ang II receptor type 1 (AT1R), as determined by reverse transcription-quantitative polymerase chain reaction and western blotting. EPO alone did not significantly reduce the high serum levels of renin and Ang II post-resuscitation, but changed the protein levels of renin and AT1R expression in myocardial tissues. However, EPO enhanced the myocardial expression of Ang II receptor type 2 (AT2R) following ROSC. In conclusion, the present study confirmed that CA resuscitation activated the renin-Ang II-AT1R signaling pathway, which may contribute to myocardial dysfunction in rats. The present study confirmed that EPO treatment is beneficial for protecting cardiac function post-resuscitation, and the roles of EPO in alleviating post-resuscitation myocardial dysfunction may potentially be associated with enhanced myocardial expression of AT2R. PMID:29393490

Myocardial metabolism during exposure to carbon monoxide in the conscious dog.

NASA Technical Reports Server (NTRS)

Adams, J. D.; Erickson, H. H.; Stone, H. L.

1973-01-01

Investigation of the relationship between coronary flow, heart rate, left ventricular function, and myocardial oxygen consumption at increasing levels of carboxyhemoglobin in conscious dogs. The results demonstrate a linear increase in coronary flow and heart rate as the carboxyhemoglobin increases up to 20%. Myocardial oxygen consumption declined during the same period.

Prevalence of scars and "mini-scars", and their impact on quality of life in Japanese patients with acne.

PubMed

Hayashi, Nobukazu; Miyachi, Yoshiki; Kawashima, Makoto

2015-07-01

There have been very few studies on the prevalence and severity of acne scars in Japanese patients. The aim of the present study was to investigate the prevalence of acne scars and their impact on the quality of life (QOL) in Japanese acne patients. Acne scars were classified as mini-scars (atrophic scars of ≥0.5 and <2 mm in diameter) atrophic scars (≥2 mm in diameter), and hypertrophic scars. The severity of acne and acne scars were evaluated. The background of patients and their QOL in relation to acne were assessed. Of 240 subjects, 218 (90.8%) had scars. All patients with scars had mini-scars; 61.2% and 14.2% of 240 had atrophic scars and hypertrophic scars, respectively. Severe scarring was found in patients who had experienced severe acne symptoms, although 15.0% of patients with scars had experienced only mild acne symptoms. The total Dermatology Life Quality Index score was significantly higher in patients with scars than in patients without scars (5.9 ± 4.4 vs 4.2 ± 4.1). Almost all the patients had small atrophic scars with a diameter of 0.5 or more and less than 2 mm, which we have termed "mini-scars". Acne scars had a negative impact on patient QOL. Early initiation of treatment is recommended to avoid acne scars. © 2015 Japanese Dermatological Association.

Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1.

PubMed

Montini, Giovanni; Zucchetta, Pietro; Tomasi, Lisanna; Talenti, Enrico; Rigamonti, Waifro; Picco, Giorgio; Ballan, Alberto; Zucchini, Andrea; Serra, Laura; Canella, Vanna; Gheno, Marta; Venturoli, Andrea; Ranieri, Marco; Caddia, Valeria; Carasi, Carla; Dall'amico, Roberto; Hewitt, Ian

2009-02-01

We examined the diagnostic accuracy of routine imaging studies (ultrasonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection. This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children < or =2 years of age, with normal prenatal ultrasound results, who completed the diagnostic follow-up evaluation (ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days, cystography within 2 months, and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring) were analyzed. Outcome measures were sensitivity, specificity, and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans. The kidneys and urinary tracts were mostly normal. The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54% of cases. Renal scarring developed in 15% of cases. The ultrasonographic and cystographic findings were poor predictors of long-term damage, showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring. The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal. Our findings support (1) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension, proteinuria, and renal function impairment (although the degree of scarring was generally minor and did not impair renal function) and (2) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation.

Effect of P144® (Anti-TGF-β) in an "In Vivo" Human Hypertrophic Scar Model in Nude Mice.

PubMed

Qiu, Shan Shan; Dotor, Javier; Hontanilla, Bernardo

2015-01-01

Hypertrophic scars are one of the most important complications in surgery due to their cosmetic and functional impairments. Previous studies in tissue fibrotic disorders have shown promising results by inhibiting the biological activity effect of Transforming Growth Factor-beta 1 (TGF-β1). The aim of the current study was to determine the clinical effect of the inhibition of TGF-β1 signaling in human hypertrophic scars implanted in nude mice by topical application of an inhibitor of TGF-β1 (P144®). A total of 30 human hypertrophic scars were implanted in 60 nude mice. The animals were divided in two groups, group A (placebo) and group B (treatment). Group C (basal) was considered as the preimplanted scar samples and they were not implanted in the nude mice. After the shedding period, topical application of a lipogel containing placebo (group A) or P144 (group B) was daily administered during two weeks. The animals were sacrificed upon completion of the study. Total area, thickness and collagen fibers area were measure and compared across all groups. Immunohistochemistry was also performed in order to quantify collagen type I and type III and elastic fiber expressions present in the dermis. Successful shedding was achieved in 83,3% of the xenografts. The mean time for shedding was 35±5.4 days. Statistically significant differences were found in the total area, collagen fibers area and thickness between the groups. Increased elastic fibers and decreased collagen I were found in the P144-treated group compared to the basal group. Topical application of an inhibitor of TGF-β1 may promote scar maturation and clinical improvement of hypertrophic scar morphology features in an "in vivo" model in nude mice after two weeks of treatment.

Glial Scar Borders Are Formed by Newly Proliferated, Elongated Astrocytes That Interact to Corral Inflammatory and Fibrotic Cells via STAT3-Dependent Mechanisms after Spinal Cord Injury

PubMed Central

Anderson, Mark A.; Song, Bingbing; Levine, Jaclynn; Fernandez, Ana; Gray-Thompson, Zachary; Ao, Yan

2013-01-01

Astroglial scars surround damaged tissue after trauma, stroke, infection, or autoimmune inflammation in the CNS. They are essential for wound repair, but also interfere with axonal regrowth. A better understanding of the cellular mechanisms, regulation, and functions of astroglial scar formation is fundamental to developing safe interventions for many CNS disorders. We used wild-type and transgenic mice to quantify and dissect these parameters. Adjacent to crush spinal cord injury (SCI), reactive astrocytes exhibited heterogeneous phenotypes as regards proliferation, morphology, and chemistry, which all varied with distance from lesions. Mature scar borders at 14 d after SCI consisted primarily of newly proliferated astroglia with elongated cell processes that surrounded large and small clusters of inflammatory, fibrotic, and other cells. During scar formation from 5 to 14 d after SCI, cell processes deriving from different astroglia associated into overlapping bundles that quantifiably reoriented and organized into dense mesh-like arrangements. Selective deletion of STAT3 from astroglia quantifiably disrupted the organization of elongated astroglia into scar borders, and caused a failure of astroglia to surround inflammatory cells, resulting in increased spread of these cells and neuronal loss. In cocultures, wild-type astroglia spontaneously corralled inflammatory or fibromeningeal cells into segregated clusters, whereas STAT3-deficient astroglia failed to do so. These findings demonstrate heterogeneity of reactive astroglia and show that scar borders are formed by newly proliferated, elongated astroglia, which organize via STAT3-dependent mechanisms to corral inflammatory and fibrotic cells into discrete areas separated from adjacent tissue that contains viable neurons. PMID:23904622

Cardiac CT for myocardial ischaemia detection and characterization--comparative analysis.

PubMed

Bucher, A M; De Cecco, C N; Schoepf, U J; Wang, R; Meinel, F G; Binukrishnan, S R; Spearman, J V; Vogl, T J; Ruzsics, B

2014-11-01

The assessment of patients presenting with symptoms of myocardial ischaemia remains one of the most common and challenging clinical scenarios faced by physicians. Current imaging modalities are capable of three-dimensional, functional and anatomical views of the heart and as such offer a unique contribution to understanding and managing the pathology involved. Evidence has accumulated that visual anatomical coronary evaluation does not adequately predict haemodynamic relevance and should be complemented by physiological evaluation, highlighting the importance of functional assessment. Technical advances in CT technology over the past decade have progressively moved cardiac CT imaging into the clinical workflow. In addition to anatomical evaluation, cardiac CT is capable of providing myocardial perfusion parameters. A variety of CT techniques can be used to assess the myocardial perfusion. The single energy first-pass CT and dual energy first-pass CT allow static assessment of myocardial blood pool. Dynamic cardiac CT imaging allows quantification of myocardial perfusion through time-resolved attenuation data. CT-based myocardial perfusion imaging (MPI) is showing promising diagnostic accuracy compared with the current reference modalities. The aim of this review is to present currently available myocardial perfusion techniques with a focus on CT imaging in light of recent clinical investigations. This article provides a comprehensive overview of currently available CT approaches of static and dynamic MPI and presents the results of corresponding clinical trials.

Functional Testing Underlying Coronary Revascularisation

ClinicalTrials.gov

2016-10-04

Multivessel Coronary Artery Disease; Vessel Disease; Stable Angina; Unstable Angina or Stabilized Non-ST Elevated Myocardial Infarction; Patients With ST-elevated Myocardial Infarction; Revascularization of Culprit Coronary Artery

An experience with trial of scar in 66 Ethiopian women.

PubMed

Sebhatu, B

1994-10-01

The purpose of this study was to determine the circumstances in which trial of scar is conducted in the obstetric unit of Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluate the safety of the undertaking in terms of maternal and perinatal morbidity and mortality. Between 11 September, 1991 to 10 September, 1992, 66 women with previous caesarean section were given a trial of scar. The main pre-requests to allow a trial of scar were: only one previous lower uterine segment section, a cephalic presentation with no disproportion in the current labour and, the presence of a functional operating theatre. Labour was being monitored by checking the uterine contractions by fundal palpation and counting the Foetal heart rate (FHR) using the Pinnard Stethoscope. Compatible blood was prior prepared in only 7 (10.6%) labours. Forty seven (71.2%) parturients delivered vaginally. In 19 (28.2%) an emergency repeat section was done for failure of progress in labour. In one (1.5%) patient, a uterine scar dehiscence was detected. The 5th minute APGAR score was 7/10 or more in 64 (94.1%) and 6/10 in 3 (4.5%) of 68 neonates. There was one prepartum intra-uterine foetal death and one neonatal death of a preterm baby making the perinatal mortality rate (PNMR) of 29.4 per thousand. There was no maternal death. In conclusion, this study demonstrates that a trial of scar was a safe procedure.

Identification of Cutaneous Functional Units Related to Burn Scar Contracture Development

DTIC Science & Technology

2009-08-01

contracture sites with the markers photographed at the beginning and end of motion. The area of skin movement associated with joint ROM was recorded...Rev. 8-98) Prescribed by ANSI Std Z39-18 volved in joint ROM relative to usual sites of burn scar contracture development. METHODS After institutional...of the body part so distortions of the skin markings did not occur on the photographic film . Each definitive movement was performed three times in

Toll-like receptor 3 plays a role in myocardial infarction and ischemia/reperfusion injury.

PubMed

Lu, Chen; Ren, Danyang; Wang, Xiaohui; Ha, Tuanzhu; Liu, Li; Lee, Eric J; Hu, Jing; Kalbfleisch, John; Gao, Xiang; Kao, Race; Williams, David; Li, Chuanfu

2014-01-01

Innate immune and inflammatory responses mediated by Toll like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. This study examined the role of TLR3 in myocardial injury induced by two models, namely, myocardial infarction (MI) and I/R. First, we examined the role of TLR3 in MI. TLR3 deficient (TLR3(-/-)) and wild type (WT) mice were subjected to MI induced by permanent ligation of the left anterior descending (LAD) coronary artery for 21days. Cardiac function was measured by echocardiography. Next, we examined whether TLR3 contributes to myocardial I/R injury. TLR3(-/-) and WT mice were subjected to myocardial ischemia (45min) followed by reperfusion for up to 3days. Cardiac function and myocardial infarct size were examined. We also examined the effect of TLR3 deficiency on I/R-induced myocardial apoptosis and inflammatory cytokine production. TLR3(-/-) mice showed significant attenuation of cardiac dysfunction after MI or I/R. Myocardial infarct size and myocardial apoptosis induced by I/R injury were significantly attenuated in TLR3(-/-) mice. TLR3 deficiency increases B-cell lymphoma 2 (BCL2) levels and attenuates I/R-increased Fas, Fas ligand or CD95L (FasL), Fas-Associated protein with Death Domain (FADD), Bax and Bak levels in the myocardium. TLR3 deficiency also attenuates I/R-induced myocardial nuclear factor KappaB (NF-κB) binding activity, Tumor necrosis factor alpha (TNF-α) and Interleukin-1 beta (IL-1β) production as well as I/R-induced infiltration of neutrophils and macrophages into the myocardium. TLR3 plays an important role in myocardial injury induced by MI or I/R. The mechanisms involve activation of apoptotic signaling and NF-κB binding activity. Modulation of TLR3 may be an effective approach for ameliorating heart injury in heart attack patients. © 2013.

Losartan treatment attenuates tumor-induced myocardial dysfunction

PubMed Central

Stevens, Sarah CW; Velten, Markus; Youtz, Dane J.; Clark, Yvonne; Jing, Runfeng; Reiser, Peter J.; Bicer, Sabahattin; Devine, Raymond; McCarthy, Donna O.; Wold, Loren E.

2015-01-01

Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT)1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Methods and Results: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8 weeks of age. Simultaneously, mice were administered Losartan (10 mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19 days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. Conclusions: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation. PMID:25988231

Losartan treatment attenuates tumor-induced myocardial dysfunction.

PubMed

Stevens, Sarah C W; Velten, Markus; Youtz, Dane J; Clark, Yvonne; Jing, Runfeng; Reiser, Peter J; Bicer, Sabahattin; Devine, Raymond D; McCarthy, Donna O; Wold, Loren E

2015-08-01

Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8weeks of age. Simultaneously, mice were administered Losartan (10mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Wear Scar Similarities between Retrieved and Simulator-Tested Polyethylene TKR Components: An Artificial Neural Network Approach

PubMed Central

2016-01-01

The aim of this study was to determine how representative wear scars of simulator-tested polyethylene (PE) inserts compare with retrieved PE inserts from total knee replacement (TKR). By means of a nonparametric self-organizing feature map (SOFM), wear scar images of 21 postmortem- and 54 revision-retrieved components were compared with six simulator-tested components that were tested either in displacement or in load control according to ISO protocols. The SOFM network was then trained with the wear scar images of postmortem-retrieved components since those are considered well-functioning at the time of retrieval. Based on this training process, eleven clusters were established, suggesting considerable variability among wear scars despite an uncomplicated loading history inside their hosts. The remaining components (revision-retrieved and simulator-tested) were then assigned to these established clusters. Six out of five simulator components were clustered together, suggesting that the network was able to identify similarities in loading history. However, the simulator-tested components ended up in a cluster at the fringe of the map containing only 10.8% of retrieved components. This may suggest that current ISO testing protocols were not fully representative of this TKR population, and protocols that better resemble patients' gait after TKR containing activities other than walking may be warranted. PMID:27597955

Relationship between carrot weevil infestation and parsley yield.

PubMed

Torres, Angel N; Hoy, Casey W

2005-08-01

The relationship between numbers of carrot weevil, Listronotus oregonensis (LeConte), oviposition scars and parsley fresh weight and plant mortality was measured in research plots during 1999 and 2000. Fresh weight was measured in one to two cuttings of parsley planted on two planting dates. The average weight declined with increasing numbers of oviposition scars in the later planting in 1999. Compensatory growth in surviving plants may reduce this effect. Plant mortality increased as number of oviposition scars per plant increased in the second planting in both years and in the first cutting of the first planting in 2000. One oviposition scar per plant is sufficient to result in significant reduction in fresh weight per plant. In commercial parsley fields, the relationship between fresh weight of parsley per 30-cm row section of parsley was best described as a linear function of the proportion of plants with root feeding. Economic damage to parsley that is equivalent to the cost of controlling carrot weevil was estimated to result from approximately 1% of plants with root damage. Based upon this estimated economic injury level, we suggest an action threshold of 1% of plants containing carrot weevil oviposition scars earlier in the growing season when controls could be applied to prevent the damage.

Pyridostigmine ameliorates cardiac remodeling induced by myocardial infarction via inhibition of the transforming growth factor-β1/TGF-β1-activated kinase pathway.

PubMed

Lu, Yi; Liu, Jin-Jun; Bi, Xue-Yuan; Yu, Xiao-Jiang; Kong, Shan-Shan; Qin, Fang-Fang; Zhou, Jun; Zang, Wei-Jin

2014-05-01

Autonomic imbalance characterized by sympathetic predominance coinciding with diminished vagal activity is an independent risk factor in cardiovascular diseases. Several studies show that vagus nerve stimulation exerted beneficial effects on cardiac function and survival. In this study, we investigated the vagomimetic effect of pyridostigmine on left ventricular (LV) remodeling in rats after myocardial infarction. After myocardial infarction, surviving rats were treated with or without pyridostigmine (31 mg·kg⁻¹·d⁻¹) for 2 weeks, and hemodynamic parameters were measured. LV tissue was used to assess infarct size and interstitial fibrosis by Masson's trichrome and 0.1% picrosirius red staining. Protein expression of heart tissues was used to assess the efficacy of the treatment. Pyridostigmine markedly reduced myocardial infarct size and improved cardiac diastolic function. These improvements were accompanied with a significant decrease in matrix metalloproteinase-2 expression and collagen deposition. Additionally, pyridostigmine inhibited both transforming growth factor-β1 (TGF-β1) and TGF-β1-activated kinase expression in hearts postmyocardial infarction. Thus, pyridostigmine reduces collagen deposition, attenuates cardiac fibrosis, and improves LV diastolic function after myocardial infarction via TGF-β1/TGF-β1-activated kinase pathway inhibition.

Effects of glycyl-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury

PubMed Central

Zhang, Yong; Yan, Hong; Lv, Shang-Gun; Wang, Lin; Liang, Guang-Ping; Wan, Qian-Xue; Peng, Xi

2013-01-01

Glutamine decreases myocardial damage in ischemia/reperfusion injury. However, the cardioprotective effect of glutamine after burn injury remains unclear. Present study was to explore the protective effect of glycyl-glutamine dipeptide on myocardial damage in severe burn rats. Seventy-two Wistar rats were randomly divided into three groups: normal control (C), burned control (B) and glycyl-glutamine dipeptide-treated (GG) groups. B and GG groups were inflicted with 30% total body surface area of full thickness burn. The GG group was given 1.5 g/kg glycyl-glutamine dipeptide per day and the B group was given the same dose of alanine via intraperitoneal injection for 3 days. The serum CK, LDH, AST, and, blood lactic acid levels, as well as the myocardium ATP and GSH contents, were measured. The indices of cardiac contractile function and histopathological change were analyzed at 12, 24, 48, and 72 post-burn hours (PBH). The serum CK, LDH, AST and blood lactic acid levels increased, and the myocardium ATP and GSH content decreased in both burned groups. Compared with B group, the CK, LDH, AST and blood lactic acid levels reduced, myocardium ATP and GSH content increased in GG group. Moreover, the inhibition of cardiac contractile function and myocardial histopathological damage were reduced significantly in GG group. We conclude that myocardial histological structure and function were damaged significantly after burn injury, glycyl-glutamine dipeptide supplementation is beneficial to myocardial preservation by improving cardiocyte energy metabolism, increasing ATP and glutathione synthesis. PMID:23638213

[Scar prophylaxis and treatment].

PubMed

Hammer-Hansen, Niels; Damsgaard, Tine Engberg; Rødgaard, Jes Christian

2015-10-12

Scarring is an expected result of trauma to the skin. Scars are a heterogenic group varying from small white non elevated scars to hypertrophic scars and keloids. Many different algorithms for scar prophylaxis and treatment have been presented in the literature. We discuss different types of scar formation and recently published evidence-based guidelines in regards to prophylaxis and treatment of scars written by 24 experts on scar management.

Left ventricular strain and its pattern estimated from cine CMR and validation with DENSE

NASA Astrophysics Data System (ADS)

Gao, Hao; Allan, Andrew; McComb, Christie; Luo, Xiaoyu; Berry, Colin

2014-07-01

Measurement of local strain provides insight into the biomechanical significance of viable myocardium. We attempted to estimate myocardial strain from cine cardiovascular magnetic resonance (CMR) images by using a b-spline deformable image registration method. Three healthy volunteers and 41 patients with either recent or chronic myocardial infarction (MI) were studied at 1.5 Tesla with both cine and DENSE CMR. Regional circumferential and radial left ventricular strains were estimated from cine and DENSE acquisitions. In all healthy volunteers, there was no difference for peak circumferential strain (- 0.18 ± 0.04 versus - 0.18 ± 0.03, p = 0.76) between cine and DENSE CMR, however peak radial strain was overestimated from cine (0.84 ± 0.37 versus 0.49 ± 0.2, p < 0.01). In the patient study, the peak strain patterns predicted by cine were similar to the patterns from DENSE, including the strain evolution related to recovery time and strain patterns related to MI scar extent. Furthermore, cine-derived strain disclosed different strain patterns in MI and non-MI regions, and regions with transmural and non-transmural MI as DENSE. Although there were large variations with radial strain measurements from cine CMR images, useful circumferential strain information can be obtained from routine clinical CMR imaging. Cine strain analysis has potential to improve the diagnostic yield from routine CMR imaging in clinical practice.

CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury

PubMed Central

Weinreuter, Martin; Kreusser, Michael M; Beckendorf, Jan; Schreiter, Friederike C; Leuschner, Florian; Lehmann, Lorenz H; Hofmann, Kai P; Rostosky, Julia S; Diemert, Nathalie; Xu, Chang; Volz, Hans Christian; Jungmann, Andreas; Nickel, Alexander; Sticht, Carsten; Gretz, Norbert; Maack, Christoph; Schneider, Michael D; Gröne, Hermann-Josef; Müller, Oliver J; Katus, Hugo A; Backs, Johannes

2014-01-01

CaMKII was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. Here, we investigated the roles of different CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury by the use of new genetic CaMKII mouse models. Although CaMKIIδC was upregulated 1 day after I/R injury, cardiac damage 1 day after I/R was neither affected in CaMKIIδ-deficient mice, CaMKIIδ-deficient mice in which the splice variants CaMKIIδB and C were re-expressed, nor in cardiomyocyte-specific CaMKIIδ/γ double knockout mice (DKO). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction, which was associated with reduced leukocyte infiltration and attenuated expression of members of the chemokine (C-C motif) ligand family, in particular CCL3 (macrophage inflammatory protein-1α, MIP-1α). Intriguingly, CaMKII was sufficient and required to induce CCL3 expression in isolated cardiomyocytes, indicating a cardiomyocyte autonomous effect. We propose that CaMKII-dependent chemoattractant signaling explains the effects on post-I/R remodeling. Taken together, we demonstrate that CaMKII is not critically involved in acute I/R-induced damage but in the process of post-infarct remodeling and inflammatory processes. PMID:25193973

The benefits of ribose in cardiovascular disease.

PubMed

Pauly, D F; Johnson, C; St Cyr, J A

2003-02-01

Cardiovascular disease still ranks as the leading cause of death in men and women. Adults have tried to lower their risk of cardiovascular disease by improving their diet, quitting smoking, controlling blood pressure and exercising regularly. Additionally, many adults have turned to nutriceutical or natural products. Myocardial ischemia, produces a depression in myocardial tissue levels of high energy compounds, along with a compromise in myocardial function. Ribose, a naturally occurring sugar, has been extensively investigated, both in animal and clinical studies, as an agent to enhance the recovery of these depressed energy compounds. Results of these studies have been promising in enhancing the recovery of these energy molecules along with an improvement in myocardial function. Therefore, ribose should be considered as a potential agent in the treatment of ischemic cardiovascular disease.

A dual flip angle 3D bSSFP magnetization transfer-like method to differentiate between recent and old myocardial infarction.

PubMed

Germain, Philippe; El Ghannudi, Soraya; Labani, Aissam; Jeung, Mi Y; Gangi, Afshin; Ohlmann, Patrick; Roy, Catherine

2018-03-01

Magnetic resonance imaging (MRI) tissue signal is modulated by magnetization transfer (MT) phenomena, intrinsically induced by balanced steady-state free precession (bSSFP) imaging. To investigate the possible value of such a MT-like bSSFP approach in two clinical settings involving focal myocardial lesions highligthed by late gadolinium enhancement (LGE+): edema induced by recent myocardial infarction (MI) and fibrotic scar related to chronic infarction. Population: 48 LGE + patients were studied: 26 with recent MI, 22 with chronic MI. 20 LGE-normal subjects were considered the control group. Field strength/sequence: Navigator-based short axis 3D-bSSFP sequences with 20° and 90° excitation flip angles were acquired (1.5T). Pixel-wise normalized MT Ratio (nMTR) parametric images were calculated according to: nMTR = 100*(S 20 -S 90 *k)/S 20 , with S 20 and S 90 signal intensity in 20° and 90° flip angle images and k = Blood 20 /Blood 90 as a normalization ratio. Statistical tests: analysis of variance (ANOVA), receiver operating characteristic (ROC) analysis. Overall normal myocardial nMTR was 50.2 ± 3.6%. In recent MI, nMTR values were significantly reduced in LGE + regions (-22.3 ± 9.9%, P < 0.0001). In cases of chronic infarct, nMTR was significantly increased in LGE + regions (14.2 ± 11.4%, P < 0.0001). Comparison between observed results and theoretical values obtained with the Freeman-Hill formula showed that most variations observed in MI are related to MT effects instead of relaxation effects. In contrast to LGE imaging, which may show a similar hyperenhancement in recent and old infarctions, nMTR imaging demonstrates an opposite pattern: decreased values for recent infarction and increased values for old infarction, thus allowing to discriminate between these two clinical conditions without gadolinium injection. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:798-808. © 2017 International Society for Magnetic Resonance in Medicine.

TGF-β improves myocardial function and prevents apoptosis induced by anoxia-reoxygenation, through the reduction of endoplasmic reticulum stress.

PubMed

Wang, Yufeng; Zong, Ligeng; Wang, Xiaolei

2016-01-01

Transforming growth factor-β (TGF-β) is known for its role in ventricular remodeling, inflammatory response, cell survival, and apoptosis. However, its role in improving myocardial function in rat hearts subjected to ischemia-reperfusion (I/R) and protecting against apoptosis induced in cardiomyocytes by anoxia-reoxygenation (A/R) has not been elucidated. This study investigated the protective effects and molecular mechanisms of TGF-β on myocardial function and cardiomyocyte apoptosis. We used TUNEL staining, we tested cell viability, and we measured mitochondrial membrane potential and levels of mitochondrial ROS after 6 h of simulated anoxia together with various durations of simulated reoxygenation in H9c2 cells. We further observed the contractile function in rat hearts after they were subjected to 30 min global ischemia and 180 min reperfusion. Pretreatment with TGF-β markedly inhibited apoptosis in H9c2 cells, as evidenced by increased cell viability and decreased numbers of TUNEL-positive cells, maintained mitochondrial membrane potential, and diminished mitochondrial production of reactive oxygen species (ROS). These changes were associated with the inhibition of endoplasmic reticulum (ER) stress-dependent markers of apoptosis (GRP78, CHOP, caspase-12, and JNK), and the modulation of the expression of Bcl2/Bax. Furthermore, TGF-β improved I/R-induced myocardial contractile dysfunction. All of these protective effects were concentration-dependent. Our results show that TGF-β prevents A/R-induced apoptosis of cardiomyocytes and improves myocardial function in rat hearts injured by I/R.

Early feasibility evaluation of thoracoscopically assisted transcatheter ventricular reconstruction in an experimental model of ischaemic heart failure with left anteroapical aneurysm.

PubMed

Cheng, Yanping; Yi, Geng-Hua; Annest, Lon S; Van Bladel, Kevin; Brown, Ryan; Wechsler, Andrew; Shibuya, Masahiko; Conditt, Gerard B; Peppas, Athanasios; Kaluza, Greg L; Granada, Juan F

2015-04-01

To test the feasibility of a thoracoscopically assisted, off-pump, transcatheter ventricular reconstruction (TCVR) approach in an ovine model of left ventricular (LV) anteroapical aneurysm. Myocardial infarction (MI) was induced by coil occlusion of the middle left anterior descending artery and diagonals. Two months after MI creation, TCVR was performed via a minimal thoracotomy in eight sheep. Under endoscopic and fluoroscopic guidance, trans-interventricular septal puncture was performed from the LV epicardial scar. A guidewire was externalised via a snare placed in the right ventricle from the external jugular vein. An internal anchor was inserted over the wire and positioned on the right ventricular septum and an external anchor was deployed on the LV anterior epicardium. Serial pairs of anchors were placed and plicated together to exclude the scar completely. Immediately after TCVR, echocardiography showed LV end-systolic volume decreased from pre-procedure 58.8±16.6 ml to 25.1±7.6 ml (p<0.01) and the ejection fraction increased from 32.0±7.3% to 52.0±7.5% (p<0.01). LV twist significantly improved (3.83±2.21 vs. pre-procedure -0.41±0.94, p=0.01) and the global peak-systolic longitudinal strain increased from -5.64% to -10.77% (p<0.05). TCVR using minimally invasive access techniques on the off-pump beating heart is feasible and resulted in significant improvement in LV performance.

Scar management.

PubMed

Edwards, Jacky

Scarring has major psychological and physical repercussions--for example, scarring on the face and visible regions of the body can be very distressing for the patient, whether it is simple acne scars or large, raised surgical or traumatic scars. This article discusses the process of scar formation, the differences between scars and proposes a number of ways in which the nurse can manage scars.

Endoscopic Versus "No-Touch" Saphenous Vein Harvesting for Coronary Artery Bypass Grafting: A Trade-Off Between Wound Healing and Graft Patency.

PubMed

Kopjar, Tomislav; Dashwood, Michael R

2016-02-01

The advantage in terms of wound infection, wound healing, and scarring has resulted in the recent adoption of endoscopic vein harvesting (EVH) as a standard of care for coronary artery bypass grafting in some centers. However, concerns regarding the quality of these grafts have been raised after recent evidence of decreased graft patency, increased reoperation rate, and myocardial infarct, problems that are associated with vascular trauma caused when using this technique. Simultaneously, an atraumatic, "no-touch" technique for harvesting the saphenous vein was developed producing grafts with improved patency comparable to the internal thoracic artery. However, wound complications remain a problem using this technique. This review outlines the need to consider the poor graft quality that may result from EVH and raises the question what is likely to be the "best practice principle" in saphenous vein harvesting? © The Author(s) 2015.

Native T1 mapping of the heart - a pictorial review.

PubMed

Germain, Philippe; El Ghannudi, Soraya; Jeung, Mi-Young; Ohlmann, Patrick; Epailly, Eric; Roy, Catherine; Gangi, Afshin

2014-01-01

T1 mapping is now a clinically feasible method, providing pixel-wise quantification of the cardiac structure's T1 values. Beyond focal lesions, well depicted by late gadolinium enhancement sequences, it has become possible to discriminate diffuse myocardial alterations, previously not assessable by noninvasive means. The strength of this method includes the high reproducibility and immediate clinical applicability, even without the use of contrast media injection (native or pre-contrast T1). The two most important determinants of native T1 augmentation are (1) edema related to tissue water increase (recent infarction or inflammation) and (2) interstitial space increase related to fibrosis (infarction scar, cardiomyopathy) or to amyloidosis. Conversely, lipid (Anderson-Fabry) or iron overload diseases are responsible for T1 reduction. In this pictorial review, the main features provided by native T1 mapping are discussed and illustrated, with a special focus on the awaited clinical purpose of this unique, promising new method.

Myocardial viability assessed with fluorodeoxyglucose and PET in patients with Q wave myocardial infarction receiving thrombolysis: relationship to coronary anatomy and ventricular function.

PubMed

Fragasso, G; Chierchia, S L; Rossetti, E; Sciammarella, M G; Conversano, A; Lucignani, G; Landoni, C; Calori, G; Margonato, A; Fazio, F

1997-03-01

In previously thrombolysed patients, we analysed residual myocardial viability using the PET-FDG technique and correlated its presence and extent to the angiographic appearance of the infarct-related vessel and left ventricular function. Thirty-six patients who had undergone intravenous thromboloysis for acute myocardial infarction 4.8 +/- 7.2 months previously were studied. Coronary angiography, left ventriculography, and assessment of myocardial perfusion and metabolism were all performed within 1 week. All patients exhibited perfusion defects consistent with the clinically identified myocardial infarction site. Residual viability, as assessed by the PET-FDG technique, was present in 53% of cases. The infarct-related coronary artery was patent in 19 (53%) patients (TIMI grade 3, 79%); of the remaining 17 with occluded infarct-related arteries, 11 had collaterals to the infarct area. Significant FDG uptake was observed in 63% of patients with a patent infarct-related artery and in 41% of those with an occluded infarct-related artery. The same study protocol was adopted in a control group of 30 patients with myocardial infarction who did not receive thrombolysis. The number of infarct-related patent vessels was significantly lower in these patients (30 vs 53%) (TIMI grade 3, 56%), but the overall percentage of PET viability was again 53%. Qualitative analysis of the regional perfusion pattern showed that the magnitude and severity of the perfusion defect was similar in the two groups, regardless of the presence or absence of FDG uptake. Global left ventricular function was also similar in the two groups. However, regional wall motion was significantly better in the thrombolysed patients with a patent infarct-related artery than in those who had not received thrombolysis and whose culprit vessel was also patent. In conclusion, the results of our study support the notion that early recanalization of the infarct-related artery is critical for preserving left ventricular function. Although the number of patent infarct-related coronary arteries is greater and left ventricular function is better in successfully thrombolysed patients, the regional metabolic pattern does not apparently correlate with the patency of the infarct-related artery. This suggests that, in "chronic' myocardial infarction, residual tissue viability as assessed by fluorodeoxyglucose uptake does not necessarily correlate with coronary recanalization.

NG2/CSPG4 and progranulin in the posttraumatic glial scar.

PubMed

Schäfer, Michael K E; Tegeder, Irmgard

2018-08-01

Traumatic injury of the central nervous system is one of the leading causes of death and disability in young adults. Failure of regeneration is caused by autonomous neuronal obstacles and by formation of the glial scar, which is essential to seal the injury but also constitutes a barrier for regrowing axons. The scar center is highly inflammatory and populated by NG2+ glia, whereas astrocytes form the sealing border and trap regrowing axons, suggesting that the non-permissive environment of activated astrocytes and extracellular matrix components is one of the reasons for the regenerative failure. Particularly, secreted chondroitin-sulfate proteoglycans, CSPGs, of the lectican family hinder axonal regrowth. In contrast, the transmembrane CSPG, NG2/CSPG4, appears to be functionally closer related to axon growth permissive heparan sulfate proteoglycans, HSPGs, and synaptic adhesion molecules, which all regulate synaptic signaling and plasticity upon alpha-secretase mediated shedding. Consequently, knockout of NG2/CSPG4 aggravates tissue loss, inflammation and neurologic deficits after brain injury, a phenotype partly mimicked by deletion of HSPG-binding proteins such as the HSPG2/perlecan-interacting protein, progranulin that is also a functional ligand of Notch and Eph2a. Indeed, structural features or progranulin's targets and NG2 may point to direct reciprocal regulations that may act in concert to overcome injury-evoked inflammation and neuronal dystrophy. This review provides an overview of the pathophysiology of the glial scar after brain injury, with a specific focus on NG2/CSPG4, its functions before and after shedding and putative reciprocal influences with the glycoprotein progranulin. Copyright © 2017 Elsevier B.V. All rights reserved.

Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia.

PubMed

Potz, Brittany A; Scrimgeour, Laura A; Pavlov, Vasile I; Sodha, Neel R; Abid, M Ruhul; Sellke, Frank W

2018-06-12

Mesenchymal stem cell-derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell-derived EV injection on cardiac function, myocardial blood flow, and vessel density in the setting of chronic myocardial ischemia. Twenty-three Yorkshire swine underwent placement of an ameroid constrictor on their left circumflex artery. Two weeks later, the animals were split into 2 groups: the control group (CON; n=7) and the EV myocardial injection group (MVM; n=10). The MVM group underwent myocardial injection of 50 μg of EVs in 2 mL 0.9% saline into the ischemic myocardium. Five weeks later, the pigs underwent a harvest procedure, and the left ventricular myocardium was analyzed. Absolute blood flow and the ischemic/nonischemic myocardial perfusion ratio were increased in the ischemic myocardium in the MVM group compared with the CON group. Pigs in the MVM group had increased capillary and arteriolar density in the ischemic myocardial tissue compared with CON pigs. There was an increase in expression of the phospho-mitogen-activated protein kinase/mitogen-activated protein kinase ratio, the phospho-endothelial nitric oxide synthase/endothelial nitric oxide synthase ratio, and total protein kinase B in the MVM group compared with CON. There was an increase in cardiac output and stroke volume in the MVM group compared with CON. In the setting of chronic myocardial ischemia, myocardial injection of human mesenchymal cell-derived EVs increases blood flow to ischemic myocardial tissue by induction of capillary and arteriolar growth via activation of the protein kinase B/endothelial nitric oxide synthase and mitogen-activated protein kinase signaling pathways resulting in increased cardiac output and stroke volume. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Development of a Porcine Full-Thickness Burn Hypertrophic Scar Model and Investigation of the Effects of Shikonin on Hypertrophic Scar Remediation

PubMed Central

Deng, Xingwang; Chen, Qian; Qiang, Lijuan; Chi, Mingwei; Xie, Nan; Wu, Yinsheng; Yao, Ming; Zhao, Dan; Ma, Jiaxiang; Zhang, Ning; Xie, Yan

2018-01-01

Hypertrophic scars formed after burns remain a challenge in clinical practice. Development of effective scar therapies relies on validated animal models that mimic human hypertrophic scars. A consistent porcine full-thickness burn hypertrophic scar model has yet to be developed. We have previously reported that Shikonin induces apoptosis and reduces collagen production in hypertrophic scar fibroblasts in vitro and may therefore hold potential as a novel scar remediation therapy. In this study, we aimed to validate the potential of Shikonin on scar remediation in vivo. A novel porcine hypertrophic scar model was created after full-thickness burn wounds, and the effect of Shikonin on scar remediation was investigated. Clinical scar assessments, histology, and immunohistochemistry were used to evaluate scar appearance, morphology, and protein expression. Eight weeks after scar formation, clinical scar assessment indicated that the score of hypertrophic scars treated with Shikonin was significantly lower than that of the control group. Hypertrophic scars treated with Shikonin appeared flat, pink, and pliable. In addition, histological analysis indicated that hypertrophic scars treated with Shikonin exhibited reduced thickness of the epidermis and dermis, thin and even epithelial layers, reduced numbers of keratinocytes, uniform distribution of fibroblasts, and a parallel and loose arrangement of collagen fibers in the dermis. Moreover, immunohistochemical analysis indicated that Shikonin inhibited the expression of p63, cytokeratin 10, alpha-smooth muscle actin, transforming growth factor-beta 1, and collagen I, which play important roles in hypertrophic scar formation. Based on these results, we conclude that Shikonin has potential as a novel scar therapy. PMID:29922164

Analysis of Frequency of Use of Different Scar Assessment Scales Based on the Scar Condition and Treatment Method

PubMed Central

Bae, Seong Hwan

2014-01-01

Analysis of scars in various conditions is essential, but no consensus had been reached on the scar assessment scale to select for a given condition. We reviewed papers to determine the scar assessment scale selected depending on the scar condition and treatment method. We searched PubMed for articles published since 2000 with the contents of the scar evaluation using a scar assessment scale with a Journal Citation Report impact factor >0.5. Among them, 96 articles that conducted a scar evaluation using a scar assessment scale were reviewed and analyzed. The scar assessment scales were identified and organized by various criteria. Among the types of scar assessment scales, the Patient and Observer Scar Assessment Scale (POSAS) was found to be the most frequently used scale. As for the assessment of newly developed operative scars, the POSAS was most used. Meanwhile, for categories depending on the treatment methods for preexisting scars, the Vancouver Scar Scale (VSS) was used in 6 studies following a laser treatment, the POSAS was used in 7 studies following surgical treatment, and the POSAS was used in 7 studies following a conservative treatment. Within the 12 categories of scar status, the VSS showed the highest frequency in 6 categories and the POSAS showed the highest frequency in the other 6 categories. According to our reviews, the POSAS and VSS are the most frequently used scar assessment scales. In the future, an optimal, universal scar scoring system is needed in order to better evaluate and treat pathologic scarring. PMID:24665417

β-Catenin–regulated myeloid cell adhesion and migration determine wound healing

PubMed Central

Amini-Nik, Saeid; Cambridge, Elizabeth; Yu, Winston; Guo, Anne; Whetstone, Heather; Nadesan, Puviindran; Poon, Raymond; Hinz, Boris; Alman, Benjamin A.

2014-01-01

A β-catenin/T cell factor–dependent transcriptional program is critical during cutaneous wound repair for the regulation of scar size; however, the relative contribution of β-catenin activity and function in specific cell types in the granulation tissue during the healing process is unknown. Here, cell lineage tracing revealed that cells in which β-catenin is transcriptionally active express a gene profile that is characteristic of the myeloid lineage. Mice harboring a macrophage-specific deletion of the gene encoding β-catenin exhibited insufficient skin wound healing due to macrophage-specific defects in migration, adhesion to fibroblasts, and ability to produce TGF-β1. In irradiated mice, only macrophages expressing β-catenin were able to rescue wound-healing deficiency. Evaluation of scar tissue collected from patients with hypertrophic and normal scars revealed a correlation between the number of macrophages within the wound, β-catenin levels, and cellularity. Our data indicate that β-catenin regulates myeloid cell motility and adhesion and that β-catenin–mediated macrophage motility contributes to the number of mesenchymal cells and ultimate scar size following cutaneous injury. PMID:24837430

Cobalt Chloride Upregulates Impaired HIF-1α Expression to Restore Sevoflurane Post-conditioning-Dependent Myocardial Protection in Diabetic Rats

PubMed Central

Wu, Jianjiang; Yang, Long; Xie, Peng; Yu, Jin; Yu, Tian; Wang, Haiying; Maimaitili, Yiliyaer; Wang, Jiang; Ma, Haiping; Yang, Yining; Zheng, Hong

2017-01-01

Previous studies from our group have demonstrated that sevoflurane post-conditioning (SPC) protects against myocardial ischemia reperfusion injury via elevating the intranuclear expression of hypoxia inducible factor-1 alpha (HIF-1α). However, diabetic SPC is associated with decreased myocardial protection and disruption of the HIF-1 signaling pathway. Previous studies have demonstrated that cobalt chloride (CoCl2) can upregulate HIF-1α expression under diabetic conditions, but whether myocardial protection by SPC can be restored afterward remains unclear. We established a rat model of type 2 diabetes and a Langendorff isolated heart model of ischemia-reperfusion injury. Prior to reperfusion, 2.4% sevoflurane was used as a post-conditioning treatment. The diabetic rats were treated with CoCl2 24 h before the experiment. At the end of reperfusion, tests were performed to assess myocardial function, infarct size, mitochondrial morphology, nitric oxide (NO), Mitochondrial reactive oxygen species (ROS), mitochondrial respiratory function and enzyme activity, HIF-1α, vascular endothelial growth factor (VEGF) and endothelial NO synthase (eNOS) protein levels. In addition, myocardial protection by SPC was monitored after the blood glucose levels were lowered by insulin. The diabetic state was associated with deficient SPC protection and decreased HIF-1α expression. After treating the diabetic rats with CoCl2, SPC significantly upregulated the expression of HIF-1α, VEGF and eNOS, which markedly improved cardiac function, NO, mitochondrial respiratory function, and enzyme activity and decreased the infarction areas and ROS. In addition, these effects were not influenced by blood glucose levels. This study proved that CoCl2activates the HIF-1α signaling pathway, which restores SPC-dependent myocardial protection under diabetic conditions, and the protective effects of SPC were independent of blood glucose levels. PMID:28659817

One-year follow-up of myocardial perfusion and function evaluated by gated SPECT MIBI in patients with earlier myocardial infarction and chronic total occlusion.

PubMed

Pavlovic, Smiljana V; Sobic-Saranovic, Dragana P; Beleslin, Branko D; Ostojic, Miodrag C; Nedeljkovic, Milan A; Giga, Vojislav L; Petrasinovic, Zorica R; Artiko, Vera M; Todorovic-Tirnanic, Mila V; Obradovic, Vladimir B

2009-01-01

Optimal treatment for chronic total occlusion (CTO) in the infarct-related coronary artery is not clear. Our aim was to assess myocardial perfusion, left ventricular ejection fraction (EF), and left ventricular size using gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging with 99mTc-methoxy-isobutyl-isonitrile in patients with CTO before and 1 year after recanalization. Thirty patients with earlier myocardial infarction and at least one CTO underwent percutaneous coronary intervention (PCI) as well as nitrate-enhanced gated SPECT myocardial perfusion and dobutamine stress echocardiography before and 11 +/- 1 months after recanalization. They were divided into three groups based on the outcome of the follow-up angiography: (i) successful recanalization with no evidence of in-stent restenosis (n=13); (ii) successful recanalization with in-stent restenosis (n=7) and (iii) unsuccessful recanalization (n=10). Overall success of recanalization for CTO was 74%. In group 1, myocardial viability was preserved in 11 of 13 (85%) patients at baseline. Gated SPECT at 1 year showed a significant decrease in perfusion abnormalities (29 +/- 12 to 23 +/- 14%, P < 0.05) and left ventricular end-diastolic volume (EDV) (168 +/- 47 to 151 +/- 47 ml, P < 0.05). Improvement in EF (51 +/- 11 to 54 +/- 13%, P > 0.05) and reduction in left ventricular end-systolic volume (ESV) (84 +/- 37 to 77 +/- 40 ml, P > 0.05) did not reach the level of significance. Myocardial viability was preserved in only two of seven patients (28%) in group 2. Neither mean perfusion abnormalities (37 +/- 24 to 35 +/- 22%, P > 0.05) nor global left ventricular parameters (EF 41 +/- 15 vs. 42 +/- 19%, EDV 298 +/- 33 vs. 299 +/- 57 mL, ESV 197 +/- 12 vs. 195 +/- 32 ml; P > 0.05) changed at the follow-up. In group 3, myocardial viability was preserved in seven of 10 patients (70%) at baseline, but no significant changes in perfusion (40 +/- 18 vs. 41 +/- 19%, P > 0.05) and left ventricular function (EF 42 +/- 17 vs. 44 +/- 14%, EDV 228 +/- 101 vs. 227 +/- 81 ml, ESV 143 +/- 87 vs. 146 +/- 8 ml; P > 0.05) were seen at the follow-up. Myocardial perfusion and EDV may significantly improve 1 year after PCI provided recanalization of CTO was successful. Our preliminary findings suggest that successful recanalization of CTO may have favorable outcome on left ventricular perfusion and function, particularly in patients with viable myocardium before PCI. The gated SPECT myocardial perfusion imaging with 99mTc-methoxy-isobutyl-isonitrile may be useful for monitoring long-term functional outcome of PCI in patients with CTO.

Hand function and quality of life before and after fasciectomy for Dupuytren contracture.

PubMed

Engstrand, Christina; Krevers, Barbro; Nylander, Göran; Kvist, Joanna

2014-07-01

To describe changes in joint motion, sensibility, and scar pliability and to investigate the patients' expectations, self-reported recovery, and satisfaction with hand function, disability, and quality of life after surgery and hand therapy for Dupuytren disease. This prospective cohort study collected measurements before surgery and 3, 6, and 12 months after surgery and hand therapy. Ninety patients with total active extension deficits of 60° or more from Dupuytren contracture were included. Outcomes measures were range of motion; sensibility; scar pliability; self-reported outcomes on expectations, recovery, and satisfaction with hand function; Disabilities of the Arm, Shoulder, and Hand scores; safety and social issues of hand function; physical activity habits; and quality of life with the Euroqol. The extension deficit decreased, and there was a transient decrease in active finger flexion during the first year after surgery. Sensibility remained unaffected. Generally, patients with surgery on multiple fingers had worse scar pliability. The majority of the patients had their expectations met, and at 6 months, 32% considered hand function as fully recovered, and 73% were satisfied with their hand function. Fear of hurting the hand and worry about not trusting the hand function were of greatest concern among safety and social issues. The Disability of the Arm, Shoulder, and Hand score and the Euroqol improved over time. After surgery and hand therapy, disability decreased independent of single or multiple operated fingers. The total active finger extension improved enough for the patients to reach a functional range of motion despite an impairment of active finger flexion still present 12 months after treatment. Therapeutic IV. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Using Local Perturbations To Manipulate and Control Pointer States in Quantum Dot Systems

NASA Astrophysics Data System (ADS)

Akis, Richard; Speyer, Gil; Ferry, David; Brunner, Roland

2012-02-01

Recently, scanning gate microscopy (SGM) was used to image scarred wave functions in an open InAs quantum dot[1]. The SGM tip provides a local potential perturbation and imaging is performed by measuring changes in conductance. Scarred wave functions, long associated with quantum chaos, have been shown in open dots to correspond to pointer states[2], eigenstates that survive the decoherence process that occurs via coupling to the environment. Pointer states modulate the conductance, yielding periodic fluctuations and the scars, normally thought unstable, are stabilized by quantum Darwinism [3]. We shall show that, beyond probing, pointer states can be manipulated by local perturbations. Particularly interesting effects occur in coupled quantum dot arrays, where a pointer state localized in one dot can be shifted over into another with a perturbation in a completely different part of the system. These nonlocal effects may perhaps be exploited to give such systems an exotic functionality. [1] A. M. Burke, R. Akis, T. E. Day, Gil Speyer, D. K. Ferry, and B. R. Bennett, Phys. Rev. Lett. 104, 176801 (2010). [2] D. K. Ferry, R. Akis, and J. P. Bird, Phys. Rev. Lett. 104, 176801 (2004). [3] R. Brunner, R. Akis,D. K. Ferry, F. Kuchar,and R. Meisels, Phys. Rev. Lett. 101, 024102 (2008).

Improved scar quality following primary and secondary healing of cutaneous wounds.

PubMed

Atiyeh, Bishara S; Amm, Christian A; El Musa, Kusai A

2003-01-01

Poor wound healing remains a critical problem in our daily practice of surgery, exerting a heavy toll on our patients as well as on the health care system. In susceptible individuals, scars can become raised, reddish, and rigid, may cause itching and pain, and might even lead to serious cosmetic and functional problems. Hypertrophic scars do not occur spontaneously in animals, which explains the lack of experimental models for the study of pathologic scar modulation. We present the results of three clinical comparative prospective studies that we have conducted. In the first study, secondary healing and cosmetic appearance following healing of partial thickness skin graft donor sites under dry (semi-open Sofra-Tulle dressing) and moist (moist exposed burn ointment, MEBO) was assessed. In the second study, healing of the donor sites was evaluated following treatment with Tegaderm or MEBO, two different types of moisture-retentive dressings. In the third study, 3 comparable groups of primarily healed wounds were evaluated. One group was treated by topical antibiotic ointment, the second group was treated by Moist Exposed Burn Ointment (MEBO), and the third group did not receive any topical treatment. In the second study, secondary healing of partial thickness skin graft donor sites was evaluated following treatment with Tegaderm or MEBO, two different types of moisture-retentive dressings. In the second and third studies, healed wounds were evaluated with the quantitative scale for scar assessment described by Beausang et al. Statistical analysis revealed that for both types of wound healing, scar quality was significantly superior in those wounds treated with MEBO.

Modulation of wound contracture alpha-smooth muscle actin and multispecific vitronectin receptor integrin alphavbeta3 in the rabbit's experimental model.

PubMed

El Kahi, Cynthia G; Atiyeh, Bishara S; Abdallah Hajj Hussein, Inaya; Jurjus, Rosalyne; Dibo, Saad A; Jurjus, Alice; Jurjus, Abdo

2009-06-01

The myofibroblast, a major component of granulation tissue, is a key cell during wound healing, tissue repair and connective tissue remodelling. Persistence of myofibroblasts within a fibrotic lesion leads to excessive scarring impairing function and aesthetics. Various wound-healing cytokines can be modulated by topical application of active agents to promote optimal wound healing and improve scar quality. Thus, the myofibroblast may represent an important target for wound-healing modulation to improve the evolution of conditions such as hypertrophic scars. The purpose of this work is to study the modulation of myofibroblasts and integrin alphavbeta3 in a full thickness wound performed on rabbits treated with different topical agents using: (1) saline, (2) Tegaderm occlusive dressing (3) silver sulfadiazine and (4) moist exposed burn ointment (MEBO). The reepithelialisation was 4 days faster in the MEBO group compared with the other therapies with less oedema formation, delayed contraction, less inflammatory cells and the lowest transepidermal water loss (TEWL) resulting in a soft scar. Although alpha-smooth muscle actin (alpha-SMA) was the highest around day 12 in the MEBO group, wound contraction and myofibroblast's activity were the least for the same period probably because of a downregulation of the integrin alphavbeta3. It seems that the effect of MEBO could be more pronounced on force transmission rather then on force generation. Greater insight into the pathology of scars may translate into non surgical treatments in the future and further work in myofibroblast biology will eventually result in efficient pharmacological tools, improving the evolution of healing and scar formation.

Magnetic resonance imaging (MRI) for the assessment of myocardial viability: an evidence-based analysis.

PubMed

2010-01-01

In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of noninvasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography.A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed.A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlPOSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based AnalysisMAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based Analysis The objective of this analysis is to assess the effectiveness and cost-effectiveness of cardiovascular magnetic resonance imaging (cardiac MRI) for the assessment of myocardial viability. To evaluate the effectiveness of cardiac MRI viability imaging, the following outcomes were examined: the diagnostic accuracy in predicting functional recovery and the impact of cardiac MRI viability imaging on prognosis (mortality and other patient outcomes). CONDITION AND TARGET POPULATION LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AND HEART FAILURE: Heart failure is a complex syndrome characterized by the heart's inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) () is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. IN GENERAL, THERE ARE THREE OPTIONS FOR THE TREATMENT OF HEART FAILURE: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or, in some cases, through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure. Left ventricular dysfunction may be permanent, due to the formation of myocardial scar, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically: dobutamine echocardiography (echo),stress echo with contrast,SPECT using either technetium or thallium,cardiac magnetic resonance imaging (cardiac MRI), andpositron emission tomography (PET). Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 - 10 µg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT: SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite directions (180 degrees) and captured by an external array of detector elements in the PET gantry. Computer software is then used to convert the radiation emission into images. The system is set up so that it only detects coincident gamma rays that arrive at the detectors within a predefined temporal window, while single photons arriving without a pair or outside the temporal window do not active the detector. This allows for increased spatial and contrast resolution. Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. (ABSTRACT TRUNCATED)

Assessment of left ventricular myocardial deformation by cardiac MRI strain imaging reveals myocardial dysfunction in patients with primary cardiac tumors.

PubMed

Chen, Jing; Yang, Zhi-Gang; Xu, Hua-Yan; Shi, Ke; Guo, Ying-Kun

2018-02-15

To assess left ventricular myocardial deformation in patients with primary cardiac tumors. MRI was retrospectively performed in 61 patients, including 31 patients with primary cardiac tumors and 30 matched normal controls. Left ventricular strain and function parameters were then assessed by MRI-tissue tracking. Differences between the tumor group and controls, left and right heart tumor groups, left ventricular wall tumor and non-left ventricular wall tumor groups, and tumors with and without LV enlargement groups were assessed. Finally, the correlations among tumor diameter, myocardial strain, and LV function were analyzed. Left ventricular myocardial strain was milder for tumor group than for normal group. Peak circumferential strain (PCS) and its diastolic strain rate, longitudinal strains (PLS) and its diastolic strain rates, and peak radial systolic and diastolic velocities of the right heart tumor group were lower than those of the left heart tumor group (all p<0.050), but the peak radial systolic strain rate of the former was higher than that of the latter (p=0.017). The corresponding strains were lower in the left ventricular wall tumor groups than in the non-left ventricular wall tumor group (p<0.050). Peak radial systolic velocities were generally higher for tumors with LV enlargement than for tumors without LV enlargement (p<0.050). Peak radial strain, PCS, and PLS showed important correlations with the left ventricular ejection fraction (all p<0.050). MRI-tissue tracking is capable of quantitatively assessing left ventricular myocardial strain to reveal sub-clinical abnormalities of myocardial contractile function. Copyright © 2017 Elsevier B.V. All rights reserved.

Endogenous sulfur dioxide aggravates myocardial injury in isolated rat heart with ischemia and reperfusion.

PubMed

Zhang, Suqing; Du, Junbao; Jin, Hongfang; Li, Wei; Liang, Yinfang; Geng, Bin; Li, Shukui; Zhang, Chunyu; Tang, Chaoshu

2009-02-27

Ischemia-reperfusion (I/R) injury is an important clinical problem. This article investigated the role of sulfur dioxide (SO2) in the regulation of cardiac function and in the pathogenesis of cardiac I/R injury in isolated rat heart. Rat hearts isolated on a Langendorff apparatus were divided into control, I/R, I/R+SO2, and I/R+hydroxamate groups. Hydroxamate is an inhibitor of SO2 synthetase. I/R treatment was ischemia for 2 hr in hypothermic solution (4 degrees C), then reperfusion/rewarming (37 degrees C) for 60 min. Cardiac function was monitored by MacLab analog to a digital converter. Determination of sulfite content involved reverse-phase high performance liquid chromatography with fluorescence detection. Myoglobin content of coronary perfusate was determined at 410 nm. Myocardial malondialdehyde (MDA) was determined by thiobarbituric acid method, and conjugated diene (CD) was extracted by chloroform. 5,50-Dithiobis-2-nitrobenzoic acid was used to determine glutathione (GSH). The results showed that I/R treatment obviously increased myocardial sulfite content, and sulfite content of myocardium was negatively correlated with the recovery rate of left-ventricle developed pressure and positively correlated with the leakage of myoglobin. In postreperfusion, myocardial function recovery was decreased by SO2. During reperfusion, myocardium-released enzymes, MDA and CD level were increased but myocardial GSH content was depressed with the treatment of SO2 donor. Incubation of myocardial tissue with SO2 significantly increased MDA and CD generation. Endogenous SO2 might be involved in the pathogenesis of myocardial I/R injury, and its mechanism might be associated with an increase in lipid peroxide level and a decrease in GSH generation.

Positron Emission Tomography for the Assessment of Myocardial Viability

PubMed Central

2010-01-01

Executive Summary In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities. After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography. A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed. The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis Magnetic Resonance Imaging for the Assessment of Myocardial Viability: An Evidence-Based Analysis Objective The objective of this analysis is to assess the effectiveness and safety of positron emission tomography (PET) imaging using F-18-fluorodeoxyglucose (FDG) for the assessment of myocardial viability. To evaluate the effectiveness of FDG PET viability imaging, the following outcomes are examined: the diagnostic accuracy of FDG PET for predicting functional recovery; the impact of PET viability imaging on prognosis (mortality and other patient outcomes); and the contribution of PET viability imaging to treatment decision making and subsequent patient outcomes. Clinical Need: Condition and Target Population Left Ventricular Systolic Dysfunction and Heart Failure Heart failure is a complex syndrome characterized by the heart’s inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD)1 is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. Treatment Options In general, there are three options for the treatment of heart failure: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure. Myocardial Viability Left ventricular dysfunction may be permanent if a myocardial scar is formed, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically: dobutamine echocardiography (echo), stress echo with contrast, SPECT using either technetium or thallium, cardiac magnetic resonance imaging (cardiac MRI), and positron emission tomography (PET). Dobutamine Echocardiography Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 – 10 μg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Stress Echocardiography with Contrast Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Cardiac Magnetic Resonance Imaging Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery. Cardiac Positron Emission Tomography Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite directions (180 degrees) and captured by an external array of detector elements in the PET gantry. Computer software is then used to convert the radiation emission into images. The system is set up so that it only detects coincident gamma rays that arrive at the detectors within a predefined temporal window, while single photons arriving without a pair or outside the temporal window do not active the detector. This allows for increased spatial and contrast resolution. Evidence-Based Analysis Research Questions What is the diagnostic accuracy of PET for detecting myocardial viability? What is the prognostic value of PET viability imaging (mortality and other clinical outcomes)? What is the contribution of PET viability imaging to treatment decision making? What is the safety of PET viability imaging? Literature Search A literature search was performed on July 17, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 to July 16, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. In addition, published systematic reviews and health technology assessments were reviewed for relevant studies published before 2004. Reference lists of included studies were also examined for any additional relevant studies not already identified. The quality of the body of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Inclusion Criteria Criteria applying to diagnostic accuracy studies, prognosis studies, and physician decision-making studies: English language full-reports Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies Patients with chronic, known CAD PET imaging using FDG for the purpose of detecting viable myocardium Criteria applying to diagnostic accuracy studies: Assessment of functional recovery ≥3 months after revascularization Raw data available to calculate sensitivity and specificity Gold standard: prediction of global or regional functional recovery Criteria applying to prognosis studies: Mortality studies that compare revascularized patients with non-revascularized patients and patients with viable and non-viable myocardium Exclusion Criteria Criteria applying to diagnostic accuracy studies, prognosis studies, and physician decision-making studies: PET perfusion imaging < 20 patients < 18 years of age Patients with non-ischemic heart disease Animal or phantom studies Studies focusing on the technical aspects of PET Studies conducted exclusively in patients with acute myocardial infarction (MI) Duplicate publications Criteria applying to diagnostic accuracy studies Gold standard other than functional recovery (e.g., PET or cardiac MRI) Assessment of functional recovery occurs before patients are revascularized Outcomes of Interest Diagnostic accuracy studies Sensitivity and specificity Positive and negative predictive values (PPV and NPV) Positive and negative likelihood ratios Diagnostic accuracy Adverse events Prognosis studies Mortality rate Functional status Exercise capacity Quality of Life Influence on PET viability imaging on physician decision making Statistical Methods Pooled estimates of sensitivity and specificity were calculated using a bivariate, binomial generalized linear mixed model. Statistical significance was defined by P values less than 0.05, where “false discovery rate” adjustments were made for multiple hypothesis testing. Using the bivariate model parameters, summary receiver operating characteristic (sROC) curves were produced. The area under the sROC curve was estimated by numerical integration with a cubic spline (default option). Finally, pooled estimates of mortality rates were calculated using weighted means. Quality of Evidence The quality of evidence assigned to individual diagnostic studies was determined using the QUADAS tool, a list of 14 questions that address internal and external validity, bias, and generalizibility of diagnostic accuracy studies. Each question is scored as “yes”, “no”, or “unclear”. The quality of the body of evidence was then assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence: High Further research is very unlikely to change confidence in the estimate of effect. Moderate Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate. Low Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate. Very Low Any estimate of effect is very uncertain Summary of Findings A total of 40 studies met the inclusion criteria and were included in this review: one health technology assessment, two systematic reviews, 22 observational diagnostic accuracy studies, and 16 prognosis studies. The available PET viability imaging literature addresses two questions: 1) what is the diagnostic accuracy of PET imaging for the assessment; and 2) what is the prognostic value of PET viability imaging. The diagnostic accuracy studies use regional or global functional recovery as the reference standard to determine the sensitivity and specificity of the technology. While regional functional recovery was most commonly used in the studies, global functional recovery is more important clinically. Due to differences in reporting and thresholds, however, it was not possible to pool global functional recovery. Functional recovery, however, is a surrogate reference standard for viability and consequently, the diagnostic accuracy results may underestimate the specificity of PET viability imaging. For example, regional functional recovery may take up to a year after revascularization depending on whether it is stunned or hibernating tissue, while many of the studies looked at regional functional recovery 3 to 6 months after revascularization. In addition, viable tissue may not recover function after revascularization due to graft patency or re-stenosis. Both issues may lead to false positives and underestimate specificity. Given these limitations, the prognostic value of PET viability imaging provides the most direct and clinically useful information. This body of literature provides evidence on the comparative effectiveness of revascularization and medical therapy in patients with viable myocardium and patients without viable myocardium. In addition, the literature compares the impact of PET-guided treatment decision making with SPECT-guided or standard care treatment decision making on survival and cardiac events (including cardiac mortality, MI, hospital stays, unintended revascularization, etc). The main findings from the diagnostic accuracy and prognosis evidence are: Based on the available very low quality evidence, PET is a useful imaging modality for the detection of viable myocardium. The pooled estimates of sensitivity and specificity for the prediction of regional functional recovery as a surrogate for viable myocardium are 91.5% (95% CI, 88.2% – 94.9%) and 67.8% (95% CI, 55.8% – 79.7%), respectively. Based the available very low quality of evidence, an indirect comparison of pooled estimates of sensitivity and specificity showed no statistically significant difference in the diagnostic accuracy of PET viability imaging for regional functional recovery using perfusion/metabolism mismatch with FDG PET plus either a PET or SPECT perfusion tracer compared with metabolism imaging with FDG PET alone. FDG PET + PET perfusion metabolism mismatch: sensitivity, 89.9% (83.5% – 96.4%); specificity, 78.3% (66.3% – 90.2%); FDG PET + SPECT perfusion metabolism mismatch: sensitivity, 87.2% (78.0% – 96.4%); specificity, 67.1% (48.3% – 85.9%); FDG PET metabolism: sensitivity, 94.5% (91.0% – 98.0%); specificity, 66.8% (53.2% – 80.3%). Given these findings, further higher quality studies are required to determine the comparative effectiveness and clinical utility of metabolism and perfusion/metabolism mismatch viability imaging with PET. Based on very low quality of evidence, patients with viable myocardium who are revascularized have a lower mortality rate than those who are treated with medical therapy. Given the quality of evidence, however, this estimate of effect is uncertain so further higher quality studies in this area should be undertaken to determine the presence and magnitude of the effect. While revascularization may reduce mortality in patients with viable myocardium, current moderate quality RCT evidence suggests that PET-guided treatment decisions do not result in statistically significant reductions in mortality compared with treatment decisions based on SPECT or standard care protocols. The PARR II trial by Beanlands et al. found a significant reduction in cardiac events (a composite outcome that includes cardiac deaths, MI, or hospital stay for cardiac cause) between the adherence to PET recommendations subgroup and the standard care group (hazard ratio, .62; 95% confidence intervals, 0.42 – 0.93; P = .019); however, this post-hoc sub-group analysis is hypothesis generating and higher quality studies are required to substantiate these findings. The use of FDG PET plus SPECT to determine perfusion/metabolism mismatch to assess myocardial viability increases the radiation exposure compared with FDG PET imaging alone or FDG PET combined with PET perfusion imaging (total-body effective dose: FDG PET, 7 mSv; FDG PET plus PET perfusion tracer, 7.6 – 7.7 mSV; FDG PET plus SPECT perfusion tracer, 16 – 25 mSv). While the precise risk attributed to this increased exposure is unknown, there is increasing concern regarding lifetime multiple exposures to radiation-based imaging modalities, although the incremental lifetime risk for patients who are older or have a poor prognosis may not be as great as for healthy individuals. PMID:23074393

Nuclear medicine in the management of patients with heart failure: guidance from an expert panel of the International Atomic Energy Agency (IAEA).

PubMed

Peix, Amalia; Mesquita, Claudio Tinoco; Paez, Diana; Pereira, Carlos Cunha; Felix, Renata; Gutierrez, Claudia; Jaimovich, Rodrigo; Ianni, Barbara Maria; Soares, Jose; Olaya, Pastor; Rodriguez, Ma Victoria; Flotats, Albert; Giubbini, Raffaele; Travin, Mark; Garcia, Ernest V

2014-08-01

Heart failure is increasing worldwide at epidemic proportions, resulting in considerable disability, mortality, and increase in healthcare costs. Gated myocardial perfusion single photon emission computed tomography or PET imaging is the most prominent imaging modality capable of providing information on global and regional ventricular function, the presence of intraventricular synchronism, myocardial perfusion, and viability on the same test. In addition, I-mIBG scintigraphy is the only imaging technique approved by various regulatory agencies able to provide information regarding the adrenergic function of the heart. Therefore, both myocardial perfusion and adrenergic imaging are useful tools in the workup and management of heart failure patients. This guide is intended to reinforce the information on the use of nuclear cardiology techniques for the assessment of heart failure and associated myocardial disease.

52 Genetic Loci Influencing Myocardial Mass

PubMed Central

van der Harst, Pim; van Setten, Jessica; Verweij, Niek; Vogler, Georg; Franke, Lude; Maurano, Matthew T.; Wang, Xinchen; Leach, Irene Mateo; Eijgelsheim, Mark; Sotoodehnia, Nona; Hayward, Caroline; Sorice, Rossella; Meirelles, Osorio; Lyytikäinen, Leo-Pekka; Polašek, Ozren; Tanaka, Toshiko; Arking, Dan E.; Ulivi, Sheila; Trompet, Stella; Müller-Nurasyid, Martina; Smith, Albert V.; Dörr, Marcus; Kerr, Kathleen F.; Magnani, Jared W.; Fabiola Del Greco, M.; Zhang, Weihua; Nolte, Ilja M.; Silva, Claudia T.; Padmanabhan, Sandosh; Tragante, Vinicius; Esko, Tõnu; Abecasis, Gonçalo R.; Adriaens, Michiel E.; Andersen, Karl; Barnett, Phil; Bis, Joshua C.; Bodmer, Rolf; Buckley, Brendan M.; Campbell, Harry; Cannon, Megan V.; Chakravarti, Aravinda; Chen, Lin Y.; Delitala, Alessandro; Devereux, Richard B.; Doevendans, Pieter A.; Dominiczak, Anna F.; Ferrucci, Luigi; Ford, Ian; Gieger, Christian; Harris, Tamara B.; Haugen, Eric; Heinig, Matthias; Hernandez, Dena G.; Hillege, Hans L.; Hirschhorn, Joel N.; Hofman, Albert; Hubner, Norbert; Hwang, Shih-Jen; Iorio, Annamaria; Kähönen, Mika; Kellis, Manolis; Kolcic, Ivana; Kooner, Ishminder K.; Kooner, Jaspal S.; Kors, Jan A.; Lakatta, Edward G.; Lage, Kasper; Launer, Lenore J.; Levy, Daniel; Lundby, Alicia; Macfarlane, Peter W.; May, Dalit; Meitinger, Thomas; Metspalu, Andres; Nappo, Stefania; Naitza, Silvia; Neph, Shane; Nord, Alex S.; Nutile, Teresa; Okin, Peter M.; Olsen, Jesper V.; Oostra, Ben A.; Penninger, Josef M.; Pennacchio, Len A.; Pers, Tune H.; Perz, Siegfried; Peters, Annette; Pinto, Yigal M.; Pfeufer, Arne; Pilia, Maria Grazia; Pramstaller, Peter P.; Prins, Bram P.; Raitakari, Olli T.; Raychaudhuri, Soumya; Rice, Ken M.; Rossin, Elizabeth J.; Rotter, Jerome I.; Schafer, Sebastian; Schlessinger, David; Schmidt, Carsten O.; Sehmi, Jobanpreet; Silljé, Herman H.W.; Sinagra, Gianfranco; Sinner, Moritz F.; Slowikowski, Kamil; Soliman, Elsayed Z.; Spector, Timothy D.; Spiering, Wilko; Stamatoyannopoulos, John A.; Stolk, Ronald P.; Strauch, Konstantin; Tan, Sian-Tsung; Tarasov, Kirill V.; Trinh, Bosco; Uitterlinden, Andre G.; van den Boogaard, Malou; van Duijn, Cornelia M.; van Gilst, Wiek H.; Viikari, Jorma S.; Visscher, Peter M.; Vitart, Veronique; Völker, Uwe; Waldenberger, Melanie; Weichenberger, Christian X.; Westra, Harm-Jan; Wijmenga, Cisca; Wolffenbuttel, Bruce H.; Yang, Jian; Bezzina, Connie R.; Munroe, Patricia B.; Snieder, Harold; Wright, Alan F.; Rudan, Igor; Boyer, Laurie A.; Asselbergs, Folkert W.; van Veldhuisen, Dirk J.; Stricker, Bruno H.; Psaty, Bruce M.; Ciullo, Marina; Sanna, Serena; Lehtimäki, Terho; Wilson, James F.; Bandinelli, Stefania; Alonso, Alvaro; Gasparini, Paolo; Jukema, J. Wouter; Kääb, Stefan; Gudnason, Vilmundur; Felix, Stephan B.; Heckbert, Susan R.; de Boer, Rudolf A.; Newton-Cheh, Christopher; Hicks, Andrew A.; Chambers, John C.; Jamshidi, Yalda; Visel, Axel; Christoffels, Vincent M.; Isaacs, Aaron; Samani, Nilesh J.; de Bakker, Paul I.W.

2017-01-01

BACKGROUND Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10−8. These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets. PMID:27659466

Effect of Relaxin Expressing Adenovirus on Scar Remodeling: A Preliminary Study

PubMed Central

Jung, Bok Ki; Lee, Won Jai; Kang, Eunhye; Ahn, Hyo Min; Kim, Yong Oock; Rah, Dong Kyun; Yun, Chae-Ok

2017-01-01

Background Relaxin is a transforming growth factor β1 antagonist. To determine the effects of relaxin on scar reduction, we investigated the scar remodeling process by injecting relaxin-expressing adenoviruses using a pig scar model. Methods Scars with full thickness were generated on the backs of Yorkshire pigs. Scars were divided into two groups (relaxin [RLX] and Control). Adenoviruses were injected into the RLX (expressing relaxin) and Control (not expressing relaxin) groups. Changes in the surface areas, color index and pliability of scars were compared. Results Fifty days after treatment, the surface areas of scars decreased, the color of scars was normalized, and the pliability of scars increased in RLX group. Conclusion Relaxin-expressing adenoviruses improved the surface area, color, and pliability of scars. The mechanism of therapeutic effects on scar formation should be further investigated. PMID:28913296

Pattern of myocardial 99mTc-HMDP uptake and impact on myocardial function in patients with transthyretin cardiac amyloidosis.

PubMed

Pradel, Sarah; Brun, Stéphanie; Victor, Gérard; Pascal, Pierre; Fournier, Pauline; Ribes, David; Lavie-Badie, Yoan; Galinier, Michel; Carrié, Didier; Berry, Isabelle; Lairez, Olivier

2018-06-07

The purpose of the study was to describe the pattern of 99m Tc-labeled phosphate agents myocardial uptake by scintigraphy and explore its impact on left ventricular (LV) functions in transthyretin cardiac amyloidosis (TTR-CA). Fifty patients with TTR-CA underwent 99m Tc- hydroxymethylene-diphosphonate ( 99m Tc-HMDP) scintigraphy and echocardiography with measure of LV thickness, longitudinal strain (LS), systolic and diastolic functions. Cardiac retention by scintigraphy was assessed by visual scoring and the heart/whole body (H/WB) ratio was calculated by dividing counts in the heart by counts in late whole-body images. The mean population age was 79 ± 10 years. Mean H/WB ratio was 12 ± 7. Myocardial 99m Tc-HMDP uptake on segments 5, 6, 7, 8, 11, 12, 13, 14, 16, and 17 was correlated with H/WB ratio. Mean LVEF and global LS were 51 ± 10% and - 10 ± 3%, respectively. H/WB ratio was correlated with global LS (R = 0.408, P = .003), Ea (R = - 0.566, P < .001) and mean left ventricular wall thickness (R = 0.476, P < .001) but not with LVEF (R = - 0.109, P = .453). Segmental myocardial uptake was slightly correlated with segmental LS (R = 0.152, P < .001). H/WB ratio was not correlated with NT-proBNP levels (R = 0.219, P = .148) neither E/Ea ratio (R = 0.204, P = .184). These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis.

Hypercholesterolemia and Myocardial function evaluated via Tissue Doppler Imaging

PubMed Central

2009-01-01

Objective To establish a link between hypercholesterolemia and myocardial dysfunction. Background Heart failure is a complex disease involving changes in systolic and diastolic function. Newer echocardiographic imaging modalities may be able to detect discreet changes in myocardial function associated with hypercholesterolemia. Therefore we sought to establish a link between hypercholesterolemia and myocardial dysfunction with tissue Doppler imaging (TDI). Methods Twenty-seven rabbits were studied: 7 were fed normal chow (group 1) and 20 a high cholesterol diet (10 with ezetimibe, 1 mg/kg/day; group 2 and 10 without, group 3). Echocardiographic images were obtained under general anesthesia. Serum cholesterol levels were obtained at baseline, 3 and 6 months and myocardial cholesterol levels measured following euthanasia. Results Doppler measurements, including E/A, E'/A' and S' were significantly lower in group 3 compared to both groups 1 and 2 but no significant differences were noted in chamber sizes or ejection fraction among the groups. Average serum cholesterol was higher in group 3 compared to groups 1 and 2 respectively (495 ± 305 mg/dl vs. 114 ± 95 mg/dl and 87 ± 37 mg/dl; p < 0.01). Myocardial cholesterol content was also higher in group 3 compared to group 2 (0.10 ± 0.04 vs. 0.06 mg/dl ± 0.02; p = 0.05). There was significant correlation between S', E'/A', E/E' and serum cholesterol (r2 = 0.17 p = 0.04, r2 = 0.37 p = 0.001 and r2 = 0.24 p = 0.01). Conclusion Cholesterol load in the serum and myocardium was significantly associated with decreased systolic and diastolic function by TDI. Moreover, lipid lowering was protective. PMID:19943937

[Effects of hypoxic acclimatization on myocardial sarcoplasmic reticulum ATPase and 45Ca2+ uptake in rats].

PubMed

Long, Chao-liang; Zhang, Yan-fang; Yin, Zhao-yun; Wang, Hai

2005-08-01

To study the effect of acute hypoxia and hypoxic acclimatization on myocardial function of rats. Eighteen male Wistar rats were randomly divided into three groups: normoxic control, acute hypoxia and intermittent hypoxic acclimatization group (n=6). After being exposed to hypoxia (8000 m) for 4 h before and after intermittent hypoxic acclimatization (3000 m and 5000 m, 14 d respectively, 4 h/d), the rats were decapitated and then myocardial sarcoplasmic reticulum (SR) were derived from cardiac muscles. Activities of Na+, K(+)-ATPase, Ca2+, Mg2(+)-ATPase in SR, phosphorylation of phospholamban (PLB) and the ability of 45Ca2+ uptake in SR were observed in all these three groups. 1) Hypoxia had no effects on the activity of Na+, K(+)-ATPase in rats myocardial SR of rats. 2) Compared with normoxic control rats, the activity of Ca2+, Mg2(+)-ATPase in myocardial SR of rats after acute hypoxia was reduced significantly (P<0.01). After intermittent hypoxic acclimatization, its activity increased significantly as compared with that of acute hypoxic rats (P<0.01). 3) The phosphorylation of PLB in acute hypoxic rats was reduced significantly compared with normoxic control rats. After intermittent hypoxic acclimatization, its phosphorylation was increased significantly compared with that of acute hypoxic rats. It suggests that hypoxic acclimatization could alleviate the inhibition of calcium pump. 4) The ability of 45Ca2+ uptake of SR in acute hypoxic rats was decreased significantly. After hypoxic acclimatization, its ability was strengthened significantly. These results suggest that the increased function of myocardial SR calcium pump, the strengthened phosphorylation of PLB to alleviate the inhibition of calcium pump and the increased function of Ca2+ transport in SR are the mechanisms of hypoxic acclimatization protecting cardiac functions from injury induced by severe hypoxia.

[Effect and mechanism of total flavonoids of bugloss on rats with myocardial ischemia and reperfusion injury].

PubMed

Xu, Xiao-Na; Niu, Zi-Ran; Wang, Shou-Bao; Chen, Yu-Cai; Gao, Li; Fang, Lian-Hu; Du, Guan-Hua

2014-06-01

This study is to investigate the effect of total flavonoids of Uygur medicine bugloss (BTF) on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending (LAD) coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg x kg(-1). Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTF. Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. ELISA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through upregulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.

An integrated platform for image-guided cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Ma, Ying Liang; Shetty, Anoop K.; Duckett, Simon; Etyngier, Patrick; Gijsbers, Geert; Bullens, Roland; Schaeffter, Tobias; Razavi, Reza; Rinaldi, Christopher A.; Rhode, Kawal S.

2012-05-01

Cardiac resynchronization therapy (CRT) is an effective procedure for patients with heart failure but 30% of patients do not respond. This may be due to sub-optimal placement of the left ventricular (LV) lead. It is hypothesized that the use of cardiac anatomy, myocardial scar distribution and dyssynchrony information, derived from cardiac magnetic resonance imaging (MRI), may improve outcome by guiding the physician for optimal LV lead positioning. Whole heart MR data can be processed to yield detailed anatomical models including the coronary veins. Cine MR data can be used to measure the motion of the LV to determine which regions are late-activating. Finally, delayed Gadolinium enhancement imaging can be used to detect regions of scarring. This paper presents a complete platform for the guidance of CRT using pre-procedural MR data combined with live x-ray fluoroscopy. The platform was used for 21 patients undergoing CRT in a standard catheterization laboratory. The patients underwent cardiac MRI prior to their procedure. For each patient, a MRI-derived cardiac model, showing the LV lead targets, was registered to x-ray fluoroscopy using multiple views of a catheter looped in the right atrium. Registration was maintained throughout the procedure by a combination of C-arm/x-ray table tracking and respiratory motion compensation. Validation of the registration between the three-dimensional (3D) roadmap and the 2D x-ray images was performed using balloon occlusion coronary venograms. A 2D registration error of 1.2 ± 0.7 mm was achieved. In addition, a novel navigation technique was developed, called Cardiac Unfold, where an entire cardiac chamber is unfolded from 3D to 2D along with all relevant anatomical and functional information and coupled to real-time device detection. This allowed more intuitive navigation as the entire 3D scene was displayed simultaneously on a 2D plot. The accuracy of the unfold navigation was assessed off-line using 13 patient data sets by computing the registration error of the LV pacing lead electrodes which was found to be 2.2 ± 0.9 mm. Furthermore, the use of Unfold Navigation was demonstrated in real-time for four clinical cases.

Platysma Flap with Z-Plasty for Correction of Post-Thyroidectomy Swallowing Deformity

PubMed Central

Jeon, Min Kyeong; Kang, Seok Joo

2013-01-01

Background Recently, the number of thyroid surgery cases has been increasing; consequently, the number of patients who visit plastic surgery departments with a chief complaint of swallowing deformity has also increased. We performed a scar correction technique on post-thyroidectomy swallowing deformity via platysma flap with Z-plasty and obtained satisfactory aesthetic and functional outcomes. Methods The authors performed operations upon 18 patients who presented a definitive retraction on the swallowing mechanism as an objective sign of swallowing deformity, or throat or neck discomfort on swallowing mechanism such as sensation of throat traction as a subjective sign after thyoridectomy from January 2009 till June 2012. The scar tissue that adhered to the subcutaneous tissue layer was completely excised. A platysma flap as mobile interference was applied to remove the continuity of the scar adhesion, and additionally, Z-plasty for prevention of midline platysma banding was performed. Results The follow-up results of the 18 patients indicated that the definitive retraction on the swallowing mechanism was completely removed. Throat or neck discomfort on the swallowing mechanism such as sensation of throat traction also was alleviated in all 18 patients. When preoperative and postoperative Vancouver scar scales were compared to each other, the scale had decreased significantly after surgery (P<0.05). Conclusions Our simple surgical method involved the formation of a platysma flap with Z-plasty as mobile interference for the correction of post-thyroidectomy swallowing deformity. This method resulted in aesthetically and functionally satisfying outcomes. PMID:23898442

Eotaxin/CCL11 levels correlate with myocardial fibrosis and mast cell density in native and transplanted rat hearts.

PubMed

Zweifel, M; Matozan, K; Dahinden, C; Schaffner, T; Mohacsi, P

2010-09-01

Myocardial fibrosis contributes to hemodynamic and cardiac functional alterations commonly observed posttransplantation. Cardiac mast cells (MC) have been linked to fibrosis in posttransplantation hearts. Eotaxin, which has been shown to be involved in fibrogenesis, has been demonstrated to be increased in production in cardiac macrophages. The aim of our study was to correlate myocardial fibrosis during heart transplant rejection in the rat with eotaxin/chemokine [c-c motif] ligand 11 (CCL11) expression, and with various subtypes of infiltrating cardiac MC, namely connective-type MC (CTMC) and mucosa-type MC (MMC). We used tissues from 2 previous studies of ongoing acute rejection in allogeneic Brown-Norway to Lewis rat and an isogeneic Brown-Norway to Brown-Norway heterotopic heart transplantation models under cyclosporin/prednisolone immunosuppression. Collagen fibrils were stained with Masson's trichrome with myocardial fibrosis expressed as percent fibrotic area per total section area. Eotaxin/CCL11 previously measured in heart tissue using enzyme-linked immunosorbent assay (ELISA) was correlated with the extent of myocardial fibrosis. We compared values from native hearts (n = 4) as well as transplants on days 5, 16, and 28 (n = 4 in each group). The area of myocardial fibrosis was significantly increased in the allogeneic compared with the isogeneic group at day 16 (38% vs 21%) and at day 28 (49% vs 22%) after transplantation. Myocardial fibrosis correlated significantly with eotaxin/CCL11 concentrations and the density of MMC, but not with CTMC in heart tissue. Eotaxin-triggered MC infiltration of the heart may contribute to myocardial fibrosis after transplantation. Targeting eotaxin/CCL11 with monoclonal antibodies, such as bertilimumab, could reduce MC infiltration, possibly resulting in decreased myocardial fibrosis and improved contractile function after heart transplantation. 2010 Elsevier Inc. All rights reserved.

Techniques for Optimizing Surgical Scars, Part 2: Hypertrophic Scars and Keloids.

PubMed

Potter, Kathryn; Konda, Sailesh; Ren, Vicky Zhen; Wang, Apphia Lihan; Srinivasan, Aditya; Chilukuri, Suneel

2017-01-01

Surgical management of benign or malignant cutaneous tumors may result in noticeable scars that are of great concern to patients, regardless of sex, age, or ethnicity. Techniques to optimize surgical scars are discussed in this three-part review. Part 2 focuses on scar revision for hypertrophic and keloids scars. Scar revision options for hypertrophic and keloid scars include corticosteroids, bleomycin, fluorouracil, verapamil, avotermin, hydrogel scaffold, nonablative fractional lasers, ablative and fractional ablative lasers, pulsed dye laser (PDL), flurandrenolide tape, imiquimod, onion extract, silicone, and scar massage.

Noninvasive laser therapy in the treatment of keloid scar after injury caused by a jellyfish: a case report

NASA Astrophysics Data System (ADS)

Kymplova, Jaroslava; Navratil, Leos; Skopek, Jiri

2001-10-01

Keloid scars trouble the patients particularly for aesthetical reasons. They also frequency result in various functional disturbances, they are painful and the patient suffers for dysesthesia on touch. Low level laser is able to provide three principal effects: biostimulating, analgesic and antiinflammatory. Particularly thanks to the first two effects we are able, when adhering to the proper therapeutic procedure, to moderate or even remove the above mentioned problems. We complement the low level laser treatment by applications of ointments, cremes or silicone strips. Our communication is aimed at a case report concerning the treatment of keloid scars resulting from an injury by a jellyfish with the aim to familiarize the reader with wide therapeutic possibilities of non-invasive laser, even in indications which are not frequently encountered in central Europe.

Inactivation of INK4a and ARF induces myocardial proliferation and improves cardiac repair following ischemia‑reperfusion.

PubMed

An, Songtao; Chen, Yan; Gao, Chuanyu; Qin, Bingyu; Du, Xianhui; Meng, Fanmin; Qi, Yanyan

2015-10-01

The growth of the heart during mammalian embryonic development is primarily dependent on an increase in the number of cardiomyocytes (CM). However, shortly following birth, CMs cease proliferating and further growth of the myocardium is achieved via hypertrophic expansion of the existing CM population. The cyclin-dependent kinase inhibitor 2A (Cdkn2a) locus encodes overlapping genes for two tumor suppressor proteins, p16INK4a and p19 alternative reading frame (ARF). To determine whether decreased Cdkn2a gene expression results in improved cardiac regeneration in vitro and in vivo following cardiac injury, the proliferation of CMs isolated from Cdkn2a knockout (KO) and wild‑type (WT) mice in vitro and in vivo were evaluated following generation of ischemia reperfusion (IR) injury. The KO mice demonstrated enhanced CM proliferation not only in vitro, but also in vivo. Furthermore, heart function was improved and scar size was decreased in the KO mice compared with that of the WT mice. The results also indicated that microRNA (miR)‑1 and miR‑195 expression levels associated with cell proliferation were reduced following IR injury in KO mice compared with those of WT mice. These results suggested that the inactivation of INK4a and ARF stimulated CM proliferation and promoted cardiac repair.

[Myocardial viability: update in nuclear cardiology].

PubMed

Vallejo, Enrique

2007-01-01

Evaluation of myocardial viability with the aid of radionuclides, is a technique that offers reliable, reproducible information, with an attractive cost-benefit relationship, in the study of the myocardial viability, integrating cardiac molecular, metabolic, and functional aspects. Nowadays, coronary risk stratification in post-myocardial infarction patients pretends to locate them as low-, intermediate, and high risk-subjects that can suffer cardiovascular complications in the very near future. Low-risk patients are characterized by a cardiac-related mortality below 1%, whereas high-risk mortality is greater than 3%. Because of clinical complications following a myocardial infarction are observed during the first month of evolution, clinical guidelines suggest to evaluate the cardiovascular risk before hospital discharge.

Control of Scar Tissue Formation in the Cornea: Strategies in Clinical and Corneal Tissue Engineering

PubMed Central

Wilson, Samantha L.; El Haj, Alicia J.; Yang, Ying

2012-01-01

Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation. PMID:24955637

Evaluation of left ventricular function using electrocardiographically gated myocardial SPECT with (123)I-labeled fatty acid analog.

PubMed

Nanasato, M; Ando, A; Isobe, S; Nonokawa, M; Hirayama, H; Tsuboi, N; Ito, T; Hirai, M; Yokota, M; Saito, H

2001-12-01

Electrocardiographically (ECG) gated myocardial SPECT with (99m)Tc-tetrofosmin has been used widely to assess left ventricular (LV) function. However, the accuracy of variables using ECG gated myocardial SPECT with beta-methyl-p-(123)I-iodophenylpentadecanoic acid (BMIPP) has not been well defined. Thirty-six patients (29 men, 7 women; mean age, 61.6 +/- 15.6 y) with ischemic heart disease underwent ECG gated myocardial SPECT with (123)I-BMIPP and with (99m)Tc-tetrofosmin and left ventriculography (LVG) within 1 wk. LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) were determined on gated SPECT using commercially available software for automatic data analysis. These volume-related items on LVG were calculated with an area-length method and were estimated by 2 independent observers to evaluate interobserver validity. The regional wall motion with these methods was assessed visually. LVEF was 41.1% +/- 12.5% on gated SPECT with (123)I-BMIPP, 44.5% +/- 13.1% on gated SPECT with (99m)Tc-tetrofosmin, and 46.0% +/- 12.7% on LVG. Global LV function and regional wall motion between both gated SPECT procedures had excellent correlation (LVEF, r = 0.943; LVEDV, r = 0.934; LVESV, r = 0.952; regional wall motion, kappa = 0.92). However, the correlations of global LV function and regional wall motion between each gated SPECT and LVG were significantly lower. Gated SPECT with (123)I-BMIPP showed the same interobserver validity as gated SPECT with (99m)Tc-tetrofosmin. Gated SPECT with (123)I-BMIPP provides high accuracy with regard to LV function and is sufficiently applicable for use in clinical SPECT. This technique can simultaneously reveal myocardial fatty acid metabolism and LV function, which may be useful to evaluate various cardiac diseases.

Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus.

PubMed

Papanastasiou, Giorgos; Williams, Michelle C; Kershaw, Lucy E; Dweck, Marc R; Alam, Shirjel; Mirsadraee, Saeed; Connell, Martin; Gray, Calum; MacGillivray, Tom; Newby, David E; Semple, Scott Ik

2015-02-17

Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods. Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value < 0.05. Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter modeling was able to detect reduced myocardial blood flow at stress (<2.5 mL/min/mL of tissue) in all 12 stenotic vessels compared to only 9 for Fermi modeling. Comparison of single bolus versus dual bolus values suggests that distributed parameter modeling is less dependent on arterial input function saturation than Fermi modeling. Distributed parameter modeling showed excellent accuracy in detecting reduced myocardial blood flow in all stenotic vessels.

Use of wave intensity analysis of carotid arteries in identifying and monitoring left ventricular systolic function dynamics in rabbits.

PubMed

Zhang, Hui; Zheng, Rongqin; Qian, Xiaoxian; Zhang, Chengxi; Hao, Baoshun; Huang, Zeping; Wu, Tao

2014-03-01

Wave intensity analysis (WIA) of the carotid artery was conducted to determine the changes that occur in left ventricular systolic function after administration of doxorubicin in rabbits. Each randomly selected rabbit was subject to routine ultrasound, WIA of the carotid artery, cardiac catheterization and pathologic examination every week and was followed for 16 wk. The first positive peak (WI1) of the carotid artery revealed that left ventricular systolic dysfunction occurred earlier than conventional indexes of heart function. WI1 was highly, positively correlated with the maximum rate of rise in left ventricular pressure in cardiac catheterization (r = 0.94, p < 0.01) and moderately negatively correlated with the apoptosis index of myocardial cells, an indicator of myocardial damage (r = -0.69, p < 0.01). Ultrasound WIA of the carotid artery sensitively reflects early myocardial damage and cardiac function, and the result is highly consistent with cardiac catheterization findings and the apoptosis index of myocardial cells. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Intravenously Delivered Mesenchymal Stem Cells: Systemic Anti-Inflammatory Effects Improve Left Ventricular Dysfunction in Acute Myocardial Infarction and Ischemic Cardiomyopathy.

PubMed

Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E

2017-05-12

Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O 2 , were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10 6 ) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10 6 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were randomized to tail-vein injection of 2×10 6 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume. Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities. © 2017 American Heart Association, Inc.

Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study.

PubMed

Mavinkurve-Groothuis, Annelies M C; Marcus, Karen A; Pourier, Milanthy; Loonen, Jacqueline; Feuth, Ton; Hoogerbrugge, Peter M; de Korte, Chris L; Kapusta, Livia

2013-06-01

The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.

The value of fractional and coronary flow reserve in predicting myocardial recovery in patients with previous myocardial infarction.

PubMed

Beleslin, Branko; Ostojic, Miodrag; Djordjevic-Dikic, Ana; Vukcevic, Vladan; Stojkovic, Sinisa; Nedeljkovic, Milan; Stankovic, Goran; Orlic, Dejan; Milic, Natasa; Stepanovic, Jelena; Giga, Vojislav; Saponjski, Jovica

2008-11-01

The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the improvement of left ventricular (LV) function in patients with previous myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). Study population consisted of 46 patients (mean age 53 +/- 7 years; 36 male) with previous MI and significant coronary stenosis undergoing PCI of infarct-related coronary artery. In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire during maximal hyperaemia before and immediately after PCI. We performed echocardiographic assessment of LV ejection fraction before and 6 months after PCI. Dobutamine stress echocardiography test was also performed before PCI. LV functional improvement was observed in 33/46 (72%) of patients. In patients with LV functional recovery in comparison with patients with no recovery, there was a significant difference in FFR before PCI (0.56 +/- 0.14 vs. 0.70 +/- 0.07, P < 0.001), improvement of FFR (0.35 +/- 0.14 vs. 0.21 +/- 0.07, P < 0.001), improvement of CFRthermo (1.3 +/- 0.6 vs. 0.5 +/- 0.3, P < 0.001), and CFRthermo after PCI (2.6 +/- 0.7 vs. 2.0 +/- 0.4, P < 0.001). When only parameters evaluated before PCI were taken into account, FFR before angioplasty (P = 0.001) and dobutamine-assessed viability (P = 0.006) were the most significant multivariate predictors of myocardial recovery. When all significant univariate parameters were evaluated, the most significant independent predictors for improvement in myocardial function were the improvement of CFRthermo during angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002). Simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI. However, the evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization and may be used as an alternative to non-invasive testing.

Early Left and Right Ventricular Response to Aortic Valve Replacement.

PubMed

Duncan, Andra E; Sarwar, Sheryar; Kateby Kashy, Babak; Sonny, Abraham; Sale, Shiva; Alfirevic, Andrej; Yang, Dongsheng; Thomas, James D; Gillinov, Marc; Sessler, Daniel I

2017-02-01

The immediate effect of aortic valve replacement (AVR) for aortic stenosis on perioperative myocardial function is unclear. Left ventricular (LV) function may be impaired by cardioplegia-induced myocardial arrest and ischemia-reperfusion injury, especially in patients with LV hypertrophy. Alternatively, LV function may improve when afterload is reduced after AVR. The right ventricle (RV), however, experiences cardioplegic arrest without benefiting from improved loading conditions. Which of these effects on myocardial function dominate in patients undergoing AVR for aortic stenosis has not been thoroughly explored. Our primary objective is thus to characterize the effect of intraoperative events on LV function during AVR using echocardiographic measures of myocardial deformation. Second, we evaluated RV function. In this supplementary analysis of 100 patients enrolled in a clinical trial (NCT01187329), 97 patients underwent AVR for aortic stenosis. Of these patients, 95 had a standardized intraoperative transesophageal echocardiographic examination of systolic and diastolic function performed before surgical incision and repeated after chest closure. Echocardiographic images were analyzed off-line for global longitudinal myocardial strain and strain rate using 2D speckle-tracking echocardiography. Myocardial deformation assessed at the beginning of surgery was compared with the end of surgery using paired t tests corrected for multiple comparisons. LV volumes and arterial blood pressure decreased, and heart rate increased at the end of surgery. Echocardiographic images were acceptable for analysis in 72 patients for LV strain, 67 for LV strain rate, and 54 for RV strain and strain rate. In 72 patients with LV strain images, 9 patients required epinephrine, 22 required norepinephrine, and 2 required both at the end of surgery. LV strain did not change at the end of surgery compared with the beginning of surgery (difference: 0.7 [97.6% confidence interval, -0.2 to 1.5]%; P = 0.07), whereas LV systolic strain rate improved (became more negative) (-0.3 [-0.4 to -0.2] s; P < 0.001). In contrast, RV systolic strain worsened (became less negative) at the end of surgery (difference: 4.6 [3.1 to 6.0]%; P < 0.001) although RV systolic strain rate was unchanged (0.0 [97.6% confidence interval, -0.1 to 0.1]; P = 0.83). LV function improved after replacement of a stenotic aortic valve demonstrated by improved longitudinal strain rate. In contrast, RV function, assessed by longitudinal strain, was reduced.

[Retrospective analysis of effects of metacarpus and phalanx traction on correction of scar contracture of hand after burn on the palm side].

PubMed

Chunsheng, Hou; Qingye, Liu; Hongfei, Hao; Yuying, Dong; Feng, Wang; Jin, Lei

2015-06-01

To analyze the effects of metacarpus and phalanx traction on correction of scar contracture of hand after burn on the palm side retrospectively. A total of 32 patients with 39 affected hands with scar contracture on the palm side after burn were hospitalized from May 2010 to December 2014. Method of treatment: scar contracture was conservatively released followed by skin grafting, which was referred to as method A; Kirschner wire was inserted into the middle or distal phalanx of finger with contracture and the corresponding metacarpus in the shape of U for 2 to 7 weeks' traction, which was referred to as method B; traction frame was built based on the traction pile and anchor formed by Kirschner wire inserted through the second to the fifth metacarpus and distal phalanx of finger with contracture, and then the affected fingers were pulled into a straight position with rubber bands for 2 to 6 months, which was referred to as method C. Method A was used in patients who would be treated with thorough release of scar followed by skin grafting routinely. Method B was used in patients who would be treated with intramedullary Kirschner wire fixation after release of scar contracture and skin transplantation routinely. Method C was further used in patients when methods A and B failed to accomplish the expected result. Method C was used in the first place followed by method A in whom there might be vascular decompensation or exposure of tendon and bone after scar release, and those who failed to meet the expectation were treated with method C in addition. Patients who were unwilling to undergo surgery were treated with method C exclusively. During the course of treatment, the presence or absence of infection and slipping of Kirschner wire or its slitting through soft tissue were observed. The presence or absence of tendency of recurrence of scar contracture within 1 to 2 weeks after treatment was observed. The length of palmar skin measuring from the root of finger with contracture to wrist crease was measured before treatment, at the termination of treatment, and 1 month after the termination of treatment. Scar condition was assessed with the Vancouver Scar Scale (VSS) before treatment and 1, 3, and 6 month(s) after the termination of treatment. Before treatment and 1 month after the termination of treatment, the range of motion was measured with the Total Active Movement (TAM) method; band function was evaluated by the Jebsen Test of Hand Function (JTHF), and the completion time was recorded. Data were processed with analysis of variance, LSD-t test, and t test. Twenty-four patients with 27 affected hands were treated with scheme A + B; 5 patients with 7 affected hands were treated with method C exclusively; 2 patients with 3 affected hands were treated with scheme A + B + C; 1 patient with 2 affected hands were treated with scheme C + A + C. During the course of treatment, no complication such as infection or slicing of tissue was observed, but there was a slight shifting of U-shaped Kirschner wire in 14 affected hands of 13 patients. Tendency of recurrence of scar contracture was observed in 11 affected hands of 10 patients, but the scar contracture did not reoccur after treatment with orthosis. The skin length of palmar side was respectively (131.8 ± 9.8) and (127.6 ± 7.5) mm at the termination of treatment and 1 month after, and they were both significantly longer than that before treatment [(114.5 ± 2.4) mm, with values respectively 10.71 and 10.39, P values below 0.001]. The score of VSS was respectively (9.8 ± 2.4), (9.7 ± 1.7), (9.3 ± 0.8), and (7.7 ± 0.5) points before treatment and 1, 3, and 6 month(s) after the termination of treatment. Only the score at 6 months after the termination of treatment was significantly lower than that before treatment (t = 3.28, P < 0.01). The ratio of excellent and good results according to method TAM was respectively 2.6% (1/39) and 94.9% (37/39) before treatment and 1 month after the termination of treatment. The time for JTHF measurement was (13.9 ± 4.1) min before treatment, and it was shortened to (11.0 ± 2.8) min 1 month after the termination of treatment (t = 3.65, P < 0.001). Single application of metacarpus and phalanx traction or its combination with skin transplantation after scar release in correcting scar contracture of the palm of hand after burn can lengthen the contracted tissue, and it is beneficial for the restoration of function and appearance of affected hand.

The Prevalence, Correlates, and Impact on Cardiac Mortality of Right Ventricular Dysfunction in Nonischemic Cardiomyopathy.

PubMed

Pueschner, Andreas; Chattranukulchai, Pairoj; Heitner, John F; Shah, Dipan J; Hayes, Brenda; Rehwald, Wolfgang; Parker, Michele A; Kim, Han W; Judd, Robert M; Kim, Raymond J; Klem, Igor

2017-10-01

This study sought to determine the prevalence, correlates, and impact on cardiac mortality of right ventricular (RV) dysfunction in nonischemic cardiomyopathy. Current heart failure guidelines place little emphasis on RV assessment due to limited available data on determinants of RV function, mechanisms leading to its failure, and relation to outcomes. We prospectively studied 423 patients with cardiac magnetic resonance (CMR). The pre-specified study endpoint was cardiac mortality. In 100 patients, right heart catheterization was performed as clinically indicated. During a median follow-up time of 6.2 years (interquartile range: 2.9 to 7.6 years), 101 patients (24%) died of cardiac causes. CMR right ventricular ejection fraction (RVEF) was a strong independent predictor of cardiac mortality after adjustment for age, heart failure-functional class, blood pressure, heart rate, serum sodium, serum creatinine, myocardial scar, and left ventricular ejection fraction (LVEF). Patients with the lowest quintile of RVEF had a nearly 5-fold higher cardiac mortality risk than did patients with the highest quintile (hazard ratio: 4.68; 95% confidence interval [CI]: 2.43 to 9.02; p < 0.0001). RVEF was positively correlated with LVEF (r = 0.60; p < 0.0001), and inversely correlated with right atrial pressure (r = -0.32; p = 0.001), pulmonary artery pressure (r = -0.34; p = 0.0005), transpulmonary gradient (r = -0.28; p = 0.006) but not with pulmonary wedge pressure (r = -0.15; p = 0.13). In multivariable logistic regression analysis of CMR, clinical, and hemodynamic data the strongest predictors of right ventricular dysfunction were LVEF (odds ratio [OR]: 0.85; 95% CI: 0.78 to 0.92; p < 0.0001), transpulmonary gradient (OR: 1.20; 95% CI: 1.09 to 1.32; p = 0.0003), and systolic blood pressure (OR: 0.97; 95% CI: 0.94 to 0.99; p = 0.02). CMR assessment of RVEF provides important prognostic information independent of established risk factors and LVEF in heart failure patients with nonischemic cardiomyopathy. Right ventricular dysfunction is strongly associated with both indices of intrinsic myocardial contractility and increased afterload from pulmonary vascular dysfunction. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A Prospective Study of Ripple Mapping the Post-Infarct Ventricular Scar to Guide Substrate Ablation for Ventricular Tachycardia.

PubMed

Luther, Vishal; Linton, Nick W F; Jamil-Copley, Shahnaz; Koa-Wing, Michael; Lim, Phang Boon; Qureshi, Norman; Ng, Fu Siong; Hayat, Sajad; Whinnett, Zachary; Davies, D Wyn; Peters, Nicholas S; Kanagaratnam, Prapa

2016-06-01

Post-infarct ventricular tachycardia is associated with channels of surviving myocardium within scar characterized by fractionated and low-amplitude signals usually occurring late during sinus rhythm. Conventional automated algorithms for 3-dimensional electro-anatomic mapping cannot differentiate the delayed local signal of conduction within the scar from the initial far-field signal generated by surrounding healthy tissue. Ripple mapping displays every deflection of an electrogram, thereby providing fully informative activation sequences. We prospectively used CARTO-based ripple maps to identify conducting channels as a target for ablation. High-density bipolar left ventricular endocardial electrograms were collected using CARTO3v4 in sinus rhythm or ventricular pacing and reviewed for ripple mapping conducting channel identification. Fifteen consecutive patients (median age 68 years, left ventricular ejection fraction 30%) were studied (6 month preprocedural implantable cardioverter defibrillator therapies: median 19 ATP events [Q1-Q3=4-93] and 1 shock [Q1-Q3=0-3]). Scar (<1.5 mV) occupied a median 29% of the total surface area (median 540 points collected within scar). A median of 2 ripple mapping conducting channels were seen within each scar (length 60 mm; initial component 0.44 mV; delayed component 0.20 mV; conduction 55 cm/s). Ablation was performed along all identified ripple mapping conducting channels (median 18 lesions) and any presumed interconnected late-activating sites (median 6 lesions; Q1-Q3=2-12). The diastolic isthmus in ventricular tachycardia was mapped in 3 patients and colocated within the ripple mapping conducting channels identified. Ventricular tachycardia was noninducible in 85% of patients post ablation, and 71% remain free of ventricular tachycardia recurrence at 6-month median follow-up. Ripple mapping can be used to identify conduction channels within scar to guide functional substrate ablation. © 2016 American Heart Association, Inc.

Outcomes of Cutaneous Scar Revision During Surgical Implant Removal in Children with Cerebral Palsy.

PubMed

Davids, Jon R; Diaz, Kevin; Leba, Thu-Ba; Adams, Samuel; Westberry, David E; Bagley, Anita M

2016-08-17

Children who have had surgery involving the placement of an implant frequently undergo a subsequent surgery for hardware removal. The cosmesis of surgical scars following initial and subsequent surgeries is unpredictable. Scar incision (subsequent surgical incision through the initial scar) or excision (around the initial scar) is selected on the basis of the quality of the initial scar. The outcomes following these techniques have not been determined. This prospective, consecutive case series was designed to compare outcomes following surgical scar incision versus excision at the time of implant removal in children with cerebral palsy. Photographs of the scars were made preoperatively and at 6 and 12 months following implant removal and were graded for scar quality utilizing the modified Stony Brook Scar Evaluation Scale (SBSES). Parental assessment of scar appearance was performed at the same time points utilizing a visual analog cosmetic scale (VACS). The scars that were selected for incision had significantly worse SBSES scores at 6 and 12 months following the second surgery compared with preoperative values. However, parents' VACS scores of the incised scars, although worse at 6 months, were comparable with preoperative scores at 12 months. Scars that were selected for excision had significantly worse SBSES scores at 6 months but scores that were comparable with preoperative values at 12 months. VACS scores for the excised scars were comparable at the 3 time points. Surgical incisions that initially healed with good scar quality generally healed well (from the parents' perspective) following subsequent incision through the previous scar. Surgical incisions that initially healed with poor scar quality did not heal better following excision of the previous scar. In such situations, surgical excision of the existing scar should occur in conjunction with additional adjuvant therapies to improve cosmesis. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

The dermatology life quality index as a means to assess life quality in patients with different scar types.

PubMed

Reinholz, M; Poetschke, J; Schwaiger, H; Epple, A; Ruzicka, T; Gauglitz, G G

2015-11-01

Measuring quality of life through questionnaires is a common method to evaluate the impact of different afflictions on the patient's well-being, especially in the field of dermatology where appearance changing afflictions are common. A variety of questionnaires has been used to distinguish different skin conditions like psoriasis, atopic dermatitis and scars. Using the Dermatology Life Quality Index (DLQI), we investigated different scar types regarding their impact on quality of life. We assessed the quality of life in 130 patients presenting to our outpatient scar clinic for the first time using the DLQI. Scars were analysed according to their clinical appearance (physiological scars, keloids, hypertrophic scars, atrophic scars, self-harm scars). Physiological scars were established as a baseline for further comparison between groups. Patients in the physiological scar group scored a mean DLQI score of 2.07 ± 3.56, patients in the keloid-, hypertrophic scar-, atrophic scar- and self-harm scar group scored values of 6.06 ± 4.00, 2.53 ± 2.48, 7.26 ± 6.72 and 12.00 ± 3.85 respectively. When compared to the baseline group the difference in the overall score for keloids was +3.99 (P < 0.001), hypertrophic scars scored +0.45 (ns), atrophic scars +5.19 (P < 0.01) and self-harm scars +9.93 (P < 0.001). Using the DLQI, we could demonstrate that different subsets of pathological scars do affect patients in a different magnitude. The DLQI provides a promising adjunct for quantifying the quality of life in patients suffering from keloids, atrophic- and self-harm scars and may constitute an interesting additional tool for monitoring the progress of scar treatments. © 2015 European Academy of Dermatology and Venereology.

Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.

PubMed

Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia; Diez-Cuñado, Marta; Zhao, Mingming; Maruyama, Sonomi; Zhu, Wenhong; Fajardo, Giovanni; Noseda, Michela; Nakamura, Kazuto; Tian, Xueying; Liu, Qiaozhen; Wang, Andrew; Matsuura, Yuka; Bushway, Paul; Cai, Wenqing; Savchenko, Alex; Mahmoudi, Morteza; Schneider, Michael D; van den Hoff, Maurice J B; Butte, Manish J; Yang, Phillip C; Walsh, Kenneth; Zhou, Bin; Bernstein, Daniel; Mercola, Mark; Ruiz-Lozano, Pilar

2015-09-24

The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans.

Cortistatin Improves Cardiac Function After Acute Myocardial Infarction in Rats by Suppressing Myocardial Apoptosis and Endoplasmic Reticulum Stress.

PubMed

Shi, Zhi-Yu; Liu, Yue; Dong, Li; Zhang, Bo; Zhao, Meng; Liu, Wen-Xiu; Zhang, Xin; Yin, Xin-Hua

2016-04-18

The endoplasmic reticulum (ER) stress-induced apoptotic pathway is associated with the development of acute myocardial infarction (AMI). Cortistatin (CST) is a novel bioactive peptide that inhibits apoptosis-related injury. Therefore, we investigated the cardioprotective effects and potential mechanisms of CST in a rat model of AMI. Male Wistar rats were randomly divided into sham, AMI, and AMI + CST groups. Cardiac function and the degree of infarction were evaluated by echocardiography, cardiac troponin I activity, and 2,3,5-triphenyl-2H-tetrazolium chloride staining after 7 days. The expression of CST, ER stress markers, and apoptotic markers was examined using immunohistochemistry and Western blotting. Compared to the AMI group, the AMI + CST group exhibited markedly better cardiac function and a lower degree of infarction. Electron microscopy and terminal deoxynucleotidyl transferase dUTP nick end labeling confirmed that myocardial apoptosis occurred after AMI. Cortistatin treatment reduced the expression of caspase 3, cleaved caspase 3, and Bax (proapoptotic proteins) and promoted the expression of Bcl-2 (antiapoptotic protein). In addition, the reduced expression of glucose-regulated protein 94 (GRP94), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding proteins homologous protein, and caspase 12 indicated that ER stress and the apoptotic pathway associated with ER stress were suppressed. Exogenous CST has a notable cardioprotective effect after AMI in a rat model in that it improves cardiac function by suppressing ER stress and myocardial apoptosis. © The Author(s) 2016.

Biventricular assist device for scombroid poisoning with refractory myocardial dysfunction: a bridge to recovery.

PubMed

Grinda, Jean-Michel; Bellenfant, Florence; Brivet, François Gilles; Carel, Yvan; Deloche, Alain

2004-09-01

We report the usefulness of biventricular mechanical circulatory support in a 36-yr-old woman with refractory myocardial dysfunction resulting from scombroid poisoning. Case report. Medical and surgical university care units. A previously healthy 36-yr-old woman with severe myocardial dysfunction unresponsive to epinephrine (1.3 microg/kg/min) and dobutamine (18 microg/kg/min) after the ingestion of cooked fresh tuna. Implantation at day 3 of a biventricular assist device consisting of two paracorporeal pneumatic pumps set at 70 beats/min to reach an output of 5.6 L/min during 8 days. The biventricular mechanical circulatory assist device allowed weaning of the inotropic drugs, maintenance of end-organ function, and support of the patient until myocardial recovery. The patient was successfully explanted 11 days after ingestion. Cardiac function had totally recovered, but a stroke was noted. At 3-yrs follow-up, there was no cardiac or neurologic sequela. This report describes severe myocardial dysfunction secondary to scombroid poisoning and demonstrates the usefulness of a mechanical circulatory assist device as a bridge to recovery.

[Oxygen-transporting function of the blood circulation system in sevoflurane anesthesia during myocardial revascularization under extracorporeal circulation].

PubMed

Skopets, A A; Lomivorotov, V V; Karakhalis, N B; Makarov, A A; Duman'ian, E S; Lomivorotova, L V

2009-01-01

The purpose of the study was to evaluate the efficiency of oxygen-transporting function of the circulatory system under sevoflurane anesthesia during myocardial revascularization operations under extracorporeal circulation. Twenty-five patients with coronary heart disease were examined. Mean blood pressure, heart rate, cardiac index, total peripheral vascular resistance index, pulmonary pressure, pulmonary wedge pressure, and central venous pressure were measured. Arterial and mixed venous blood oxygen levels, oxygen delivery and consumption index, arteriovenous oxygen difference, and glucose and lactate concentrations were calculated. The study has demonstrated that sevoflurane is an effective and safe anesthetic for myocardial revascularization operations in patients with coronary heart disease. The use of sevoflurane contributes to steady-state oxygen-transporting function of the circulatory system at all surgical stages.

Relationship of biomarkers of extracellular matrix with myocardial function in Type 2 diabetes mellitus.

PubMed

Liu, Ju-Hua; Chen, Yan; Zhen, Zhe; Ho, Lai-Ming; Tsang, Anita; Yuen, Michele; Lam, Karen; Tse, Hung-Fat; Yiu, Kai-Hang

2017-07-01

The study evaluated the relationship of extracellular matrix and renin angiotensin system with myocardial dysfunction in Type 2 diabetes mellitus. All patients underwent resting and exercise echocardiography, including conventional parameters, E/E' ratio, global longitudinal strain and diastolic function reserve index. Plasma matrix metalloproteinase-1, TIMP-1, amino-terminal propeptide of type I and type III procollagen and renin angiotensin system activity were measured. As patients with diastolic dysfunction had a higher plasma level of TIMP-1 and propeptide of type III procollagen than those with no diastolic dysfunction. After multivariate adjustment, TIMP-1 associated with E/E' (both at rest and stress) and diastolic function reserve index. TIMP-1 is independently associated with myocardial diastolic dysfunction in patients with Type 2 diabetes mellitus.

The role of a structured exercise training program on cardiac structure and function after acute myocardial infarction: study protocol for a randomized controlled trial.

PubMed

Fontes-Carvalho, Ricardo; Sampaio, Francisco; Teixeira, Madalena; Gama, Vasco; Leite-Moreira, Adelino F

2015-03-12

Exercise training is effective in improving functional capacity and quality of life in patients with coronary artery disease, but its effects on left ventricular systolic and diastolic function are controversial. Diastolic dysfunction is a major determinant of adverse outcome after myocardial infarction and, contrary to systolic function, no therapy or intervention has proved to significantly improve diastolic function. Data from animal studies and from patients with diastolic heart failure has suggested that exercise training can have a positive effect on diastolic function parameters. This trial aims to evaluate if a structured exercise training program can improve resting left ventricular diastolic and systolic function in patients who have had an acute myocardial infarction. This is a phase II, prospective, randomized, open-label, blinded-endpoint trial that will include at least 96 consecutive patients who have had an acute myocardial infarction one month previously. Patients will be randomized (1:1) to an exercise training program or a control group, receiving standard of care. At enrolment, and at the end of the follow-up period, patients will be submitted to an echocardiography (with detailed assessment of diastolic and systolic function using recent consensus guidelines), cardiopulmonary exercise testing, an anthropometric assessment, blood testing, and clinical evaluation. Patients randomized to the intervention group will be submitted to an eight-week outpatient exercise program, combining endurance and resistance training, for three sessions per week. The primary endpoint will be the change in lateral E' velocity immediately after the eight-week exercise training program. Secondary endpoints will include other echocardiographic parameters of left ventricular diastolic and systolic function, cardiac structure, metabolic and inflammation biomarkers (high-sensitivity C-reactive protein and pro-BNP), functional capacity (peak oxygen consumption and anaerobic threshold) and anthropometric measurements. New strategies that can improve left ventricular diastolic function are clinically needed. This will be the first trial to evaluate, in patients who have had an acute myocardial infarction, the effects of a structured program of exercise training on diastolic and systolic function, assessed by novel echocardiographic parameters. Registered with ClinicalTrials.gov (reference: NCT02224495 ) on 21 August 2014.

The Role of Echocardiography in Coronary Artery Disease and Acute Myocardial Infarction

PubMed Central

Esmaeilzadeh, Maryam; Parsaee, Mozhgan; Maleki, Majid

2013-01-01

Echocardiography is a non-invasive diagnostic technique which provides information regarding cardiac function and hemodynamics. It is the most frequently used cardiovascular diagnostic test after electrocardiography and chest X-ray. However, in a patient with acute chest pain, Transthoracic Echocardiography is essential both for diagnosing acute coronary syndrome, zeroing on the evaluation of ventricular function and the presence of regional wall motion abnormalities, and for ruling out other etiologies of acute chest pain or dyspnea, including aortic dissection and pericardial effusion. Echocardiography is a versatile imaging modality for the management of patients with chest pain and assessment of left ventricular systolic function, diastolic function, and even myocardial and coronary perfusion and is, therefore, useful in the diagnosis and triage of patients with acute chest pain or dyspnea. This review has focused on the current applications of echocardiography in patients with coronary artery disease and myocardial infarction. PMID:23646042

Quantitative myocardial perfusion from static cardiac and dynamic arterial CT

NASA Astrophysics Data System (ADS)

Bindschadler, Michael; Branch, Kelley R.; Alessio, Adam M.

2018-05-01

Quantitative myocardial blood flow (MBF) estimation by dynamic contrast enhanced cardiac computed tomography (CT) requires multi-frame acquisition of contrast transit through the blood pool and myocardium to inform the arterial input and tissue response functions. Both the input and the tissue response functions for the entire myocardium are sampled with each acquisition. However, the long breath holds and frequent sampling can result in significant motion artifacts and relatively high radiation dose. To address these limitations, we propose and evaluate a new static cardiac and dynamic arterial (SCDA) quantitative MBF approach where (1) the input function is well sampled using either prediction from pre-scan timing bolus data or measured from dynamic thin slice ‘bolus tracking’ acquisitions, and (2) the whole-heart tissue response data is limited to one contrast enhanced CT acquisition. A perfusion model uses the dynamic arterial input function to generate a family of possible myocardial contrast enhancement curves corresponding to a range of MBF values. Combined with the timing of the single whole-heart acquisition, these curves generate a lookup table relating myocardial contrast enhancement to quantitative MBF. We tested the SCDA approach in 28 patients that underwent a full dynamic CT protocol both at rest and vasodilator stress conditions. Using measured input function plus single (enhanced CT only) or plus double (enhanced and contrast free baseline CT’s) myocardial acquisitions yielded MBF estimates with root mean square (RMS) error of 1.2 ml/min/g and 0.35 ml/min/g, and radiation dose reductions of 90% and 83%, respectively. The prediction of the input function based on timing bolus data and the static acquisition had an RMS error compared to the measured input function of 26.0% which led to MBF estimation errors greater than threefold higher than using the measured input function. SCDA presents a new, simplified approach for quantitative perfusion imaging with an acquisition strategy offering substantial radiation dose and computational complexity savings over dynamic CT.

Use of paper for treatment of a peripheral nerve trauma in the rat.

PubMed

Kauppila, T; Jyväsjärvi, E; Murtomäki, S; Mansikka, H; Pertovaara, A; Virtanen, I; Liesi, P

1997-09-29

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

Midcervical scar satisfaction in thyroidectomy patients.

PubMed

Best, Amy R; Shipchandler, Taha Z; Cordes, Susan R

2017-05-01

Assess long-term patient satisfaction with conventional thyroidectomy scars and the impact of thyroidectomy scars on patient quality of life. Validated survey administration and retrospective review of clinical and demographic data. Patients who underwent conventional thyroidectomy through years 2000 to 2010 were identified and administered the validated Patient Scar Assessment Questionnaire. Mean satisfaction, appearance and scar-consciousness scores were determined. Thirty-seven patients also measured the length of their current scar. Patient demographic and operative data were collected retrospectively from the medical record. Data were analyzed with one-way analysis of variance and independent samples t testing. Sixty of 69 patients perceived the appearance of their scar to be "good" or "excellent." Sixty-three patients (91.3%) were satisfied with all scar outcomes; 67 (97.1%) were satisfied with the overall appearance of their scar. Mean total satisfaction score was 17.3 (<26 indicates a high level of satisfaction). Fifty-six (81.2%) were "not at all" self-conscious of their scar; 65 (94.2%) reported no attempt to hide their scar. Seven patients (10.1%) indicated any likelihood of pursuing scar revision. Females had significantly higher total satisfaction scores, consciousness scores, and satisfaction with appearance scores. The effect of perceived scar length was significant for scar-consciousness, not patient satisfaction. The majority of patients were satisfied with their thyroidectomy scar appearance. Few patients reported a desire to hide the scar or pursue revision. Women were more likely to be dissatisfied than men. Length may play a role in scar consciousness. 4 Laryngoscope, 127:1247-1252, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Nuclear medicine in the management of patients with heart failure: guidance from an expert panel of the International Atomic Energy Agency (IAEA)

PubMed Central

Peix, Amalia; Mesquita, Claudio Tinoco; Paez, Diana; Pereira, Carlos Cunha; Felix, Renata; Gutierrez, Claudia; Jaimovich, Rodrigo; Ianni, Barbara Maria; Soares, Jose; Olaya, Pastor; Rodriguez, Ma. Victoria; Flotats, Albert; Giubbini, Raffaele; Travin, Mark

2014-01-01

Heart failure is increasing worldwide at epidemic proportions, resulting in considerable disability, mortality, and increase in healthcare costs. Gated myocardial perfusion single photon emission computed tomography or PET imaging is the most prominent imaging modality capable of providing information on global and regional ventricular function, the presence of intraventricular synchronism, myocardial perfusion, and viability on the same test. In addition, 123I-mIBG scintigraphy is the only imaging technique approved by various regulatory agencies able to provide information regarding the adrenergic function of the heart. Therefore, both myocardial perfusion and adrenergic imaging are useful tools in the workup and management of heart failure patients. This guide is intended to reinforce the information on the use of nuclear cardiology techniques for the assessment of heart failure and associated myocardial disease. PMID:24781009

Emerging Therapies for Scar Prevention

PubMed Central

Block, Lisa; Gosain, Ankush; King, Timothy W.

2015-01-01

Significance: There are ∼12 million traumatic lacerations treated in the United States emergency rooms each year, 250 million surgical incisions created worldwide every year, and 11 million burns severe enough to warrant medical treatment worldwide. In the United States, over $20 billion dollars per year are spent on the treatment and management of scars. Recent Advances: Investigations into the management of scar therapies over the last decade have advanced our understanding related to the care of cutaneous scars. Scar treatment methods are presented including topical, intralesional, and mechanical therapies in addition to cryotherapy, radiotherapy, and laser therapy. Critical Issues: Current treatment options for scars have significant limitations. This review presents the current and emerging therapies available for scar management and the scientific evidence for scar management is discussed. Future Directions: Based upon our new understanding of scar formation, innovative scar therapies are being developed. Additional research on the basic science of scar formation will lead to additional advances and novel therapies for the treatment of cutaneous scars. PMID:26487979

Identification of cardiomyopathy associated circulating miRNA biomarkers in patients with muscular dystrophy using a complementary cardiovascular magnetic resonance and plasma profiling approach.

PubMed

Becker, Svetlana; Florian, Anca; Patrascu, Alexandru; Rösch, Sabine; Waltenberger, Johannes; Sechtem, Udo; Schwab, Matthias; Schaeffeler, Elke; Yilmaz, Ali

2016-05-06

Duchenne and Becker muscular dystrophy (DMD and BMD) are X-chromosomal recessive neuromuscular disorders that are caused by mutations in the dystrophin gene and characterized by cardiac involvement. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers for various cardiovascular diseases. However, circulating miRNAs reflecting the presence and/or disease severity of cardiac involvement in DMD/BMD patients have not been described so far. Sixty-three male patients with known MD and 26 age-matched healthy male controls were prospectively enrolled. All MD patients and controls underwent comprehensive cardiovascular magnetic resonance (CMR) studies as well as venous blood sampling on the same day. An impaired left ventricular (LV) systolic function (defined as LV-EF <55 %) was detected in 29 (46 %) and presence of late gadolinium enhancement (LGE) indicative of myocardial fibrosis in 48 (76 %) MD patients with an exclusively non-ischemic pattern. Whereas no significant differences were observed for the 27 selected circulating miRNAs in MD patients with abnormal CMR findings (comprising structural and/or functional impairments) compared to those with completely normal CMR studies, a significant up-regulation of three miRNAs was observed in LGE-positive MD patients compared to LGE-negative ones: miR-222 (1.8-fold, p = 0.035), miR-26a (2.1-fold, p = 0.03) and miR-378a-5p (2.4-fold, p = 0.026). A signature of these three miRNAs (miR-26a, miR-222 and miR-378a-5p) resulted in an area under the curve (AUC) value of 0.74 for the diagnosis of LGE-positive MD patients. In a multivariable model, three independent predictors for LGE presence were identified comprising not only clinical and laboratory markers (LV-EF: OR 0.47, 95 % CI 0.24-0.89, p = 0.021 and elevated hs-Trop: OR 2559, 95 % CI 2.97-22.04*10(5), p = 0.023) but also the circulating miR-222 (OR 938, 95 % CI 938.46, 3.56-24.73*10(4), p = 0.016). Up-regulation of circulating miRNAs miR-222, miR-26a and miR-378a-5p indicates the presence of myocardial scars in MD patients. Plasma miR-222 appears to be a promising novel biomarker reflecting structural - but not functional - cardiac alterations in MD patients.

The role of massage in scar management: a literature review.

PubMed

Shin, Thuzar M; Bordeaux, Jeremy S

2012-03-01

Many surgeons recommend postoperative scar massage to improve aesthetic outcome, although scar massage regimens vary greatly. To review the regimens and efficacy of scar massage. PubMed was searched using the following key words: "massage" in combination with "scar," or "linear," "hypertrophic," "keloid," "diasta*," "atrophic." Information on study type, scar type, number of patients, scar location, time to onset of massage therapy, treatment protocol, treatment duration, outcomes measured, and response to treatment was tabulated. Ten publications including 144 patients who received scar massage were examined in this review. Time to treatment onset ranged from after suture removal to longer than 2 years. Treatment protocols ranged from 10 minutes twice daily to 30 minutes twice weekly. Treatment duration varied from one treatment to 6 months. Overall, 65 patients (45.7%) experienced clinical improvement based on Patient Observer Scar Assessment Scale score, Vancouver Scar Scale score, range of motion, pruritus, pain, mood, depression, or anxiety. Of 30 surgical scars treated with massage, 27 (90%) had improved appearance or Patient Observer Scar Assessment Scale score. The evidence for the use of scar massage is weak, regimens used are varied, and outcomes measured are neither standardized nor reliably objective, although its efficacy appears to be greater in postsurgical scars than traumatic or postburn scars. Although scar massage is anecdotally effective, there is scarce scientific data in the literature to support it. © 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Scar revision

PubMed Central

Sharma, Mohit; Wakure, Abhijeet

2013-01-01

Most surgical patients end up with a scar and most of these would want at least some improvement in the appearance of the scar. Using sound techniques for wound closure surgeons can, to a certain extent, prevent suboptimal scars. This article reviews the principles of prevention and treatment of suboptimal scars. Surgical techniques of scar revision, i.e., Z plasty, W plasty, and geometrical broken line closure are described. Post-operative care and other adjuvant therapies of scars are described. A short description of dermabrasion and lasers for management of scars is given. It is hoped that this review helps the surgeon to formulate a comprehensive plan for management of scars of these patients. PMID:24516292

Fetal Cortical Transplants in Adult Rats Subjected to Experimental Brain Injury

PubMed Central

Soares, Holly; McIntosh, Tracy K.

1991-01-01

Fetal cortical tissue was injected into injured adult rat brains following concussive fluid percussion (FP) brain injury. Rats subjected to moderate FP injury received E16 cortex transplant injections into lesioned motor cortex 2 days, 1 week, 2 weeks, and 4 weeks post injury. Histological assessment of transplant survival and integration was based upon Nissl staining, glial fibrillary acidic protein (GFAP) immunocytochemistry, and staining for acetylcholinesterase. In addition to histological analysis, the ability of the transplants to attenuate neurological motor deficits associated with concussive FP brain injury was also tested. Three subgroups of rats receiving transplant 1 week, 2 weeks, and 4 weeks post injury Were chosen for evaluation of neurological motor function. Fetal cortical tissue injected into the injury site 4 weeks post injury failed to incorporate with injured host brain, did not affect glial scar formation, and exhibited extensive GFAP immunoreactivity. No improvement in neurological motor function was observed in animals receiving transplants 4 weeks post injury. Conversely, transplants injected 2 days, 1 week, or 2 weeks post injury survived, incorporated with host brain, exhibited little GFAP immunoreactivity, and successfully attenuated glial scarring. However, no significant improvement in motor function was observed at the one week or two week time points. The inability of the transplants to attenuate motor function may indicate inappropriate host/transplant interaction. Our results demonstrate that there exists a temporal window in which fetal cortical transplants can attenuate glial scarring as well as be successfully incorporated into host brains following FP injury. PMID:1782253

Clinical Study of NeuroRegen Scaffold Combined with Human Mesenchymal Stem Cells for the Repair of Chronic Complete Spinal Cord Injury

PubMed Central

Zhao, Yannan; Tang, Fengwu; Xiao, Zhifeng; Han, Guang; Wang, Nuo; Yin, Na; Chen, Bing; Jiang, Xianfeng; Yun, Chen; Han, Wanjun; Zhao, Changyu; Cheng, Shixiang; Zhang, Sai; Dai, Jianwu

2017-01-01

Regeneration of damaged neurons and recovery of sensation and motor function after complete spinal cord injury (SCI) are challenging. We previously developed a collagen scaffold, NeuroRegen, to promote axonal growth along collagen fibers and inhibit glial scar formation after SCI. When functionalized with multiple biomolecules, this scaffold promoted neurological regeneration and functional recovery in animals with SCI. In this study, eight patients with chronic complete SCI were enrolled to examine the safety and efficacy of implanting NeuroRegen scaffold with human umbilical cord mesenchymal stem cells (hUCB-MSCs). Using intraoperative neurophysiological monitoring, we identified and surgically resected scar tissues to eliminate the inhibitory effect of glial scarring on nerve regeneration. We then implanted NeuroRegen scaffold loaded with hUCB-MSCs into the resection sites. No adverse events (infection, fever, headache, allergic reaction, shock, perioperative complications, aggravation of neurological status, or cancer) were observed during 1 year of follow-up. Primary efficacy outcomes, including expansion of sensation level and motor-evoked potential (MEP)-responsive area, increased finger activity, enhanced trunk stability, defecation sensation, and autonomic neural function recovery, were observed in some patients. Our findings suggest that combined application of NeuroRegen scaffold and hUCB-MSCs is safe and feasible for clinical therapy in patients with chronic SCI. Our study suggests that construction of a regenerative microenvironment using a scaffold-based strategy may be a possible future approach to SCI repair. PMID:28185615

A paired comparison analysis of third-party rater thyroidectomy scar preference.

PubMed

Rajakumar, C; Doyle, P C; Brandt, M G; Moore, C C; Nichols, A; Franklin, J H; Yoo, J; Fung, K

2017-01-01

To determine the length and position of a thyroidectomy scar that is cosmetically most appealing to naïve raters. Images of thyroidectomy scars were reproduced on male and female necks using digital imaging software. Surgical variables studied were scar position and length. Fifteen raters were presented with 56 scar pairings and asked to identify which was preferred cosmetically. Twenty duplicate pairings were included to assess rater reliability. Analysis of variance was used to determine preference. Raters preferred low, short scars, followed by high, short scars, with long scars in either position being less desirable (p < 0.05). Twelve of 15 raters had acceptable intra-rater and inter-rater reliability. Naïve raters preferred low, short scars over the alternatives. High, short scars were the next most favourably rated. If other factors influencing incision choice are considered equal, surgeons should consider these preferences in scar position and length when planning their thyroidectomy approach.

Local sympathetic denervation attenuates myocardial inflammation and improves cardiac function after myocardial infarction in mice

PubMed Central

Ziegler, Karin A; Ahles, Andrea; Wille, Timo; Kerler, Julia; Ramanujam, Deepak; Engelhardt, Stefan

2018-01-01

Abstract Aims Cardiac inflammation has been suggested to be regulated by the sympathetic nervous system (SNS). However, due to the lack of methodology to surgically eliminate the myocardial SNS in mice, neuronal control of cardiac inflammation remains ill-defined. Here, we report a procedure for local cardiac sympathetic denervation in mice and tested its effect in a mouse model of heart failure post-myocardial infarction. Methods and results Upon preparation of the carotid bifurcation, the right and the left superior cervical ganglia were localized and their pre- and postganglionic branches dissected before removal of the ganglion. Ganglionectomy led to an almost entire loss of myocardial sympathetic innervation in the left ventricular anterior wall. When applied at the time of myocardial infarction (MI), cardiac sympathetic denervation did not affect acute myocardial damage and infarct size. In contrast, cardiac sympathetic denervation significantly attenuated chronic consequences of MI, including myocardial inflammation, myocyte hypertrophy, and overall cardiac dysfunction. Conclusion These data suggest a critical role for local sympathetic control of cardiac inflammation. Our model of myocardial sympathetic denervation in mice should prove useful to further dissect the molecular mechanisms underlying cardiac neural control. PMID:29186414

Functional characterization of TRAP1-like protein involved in modulating fibrotic processes mediated by TGF-β/Smad signaling in hypertrophic scar fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, X.; Department of Pediatric Surgery, Shanghai Children’s Medical Center, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127; Chu, J.

2015-03-15

The transforming growth factor-β1 (TGF-β)-mediated signaling pathway is believed to be closely associated with wound healing and scar formation, in which TRAP1-like protein (TLP) plays a role in regulating the balance of Smad2 vs. Smad3 signaling. Our previous study revealed the relation between TLP and collagen synthesis in normal human skin fibroblasts. Here, we present a detailed analysis of the effects of TLP on the process of hypertrophic scar formation and contraction. To explore and verify a contribution of TLP to the pathological mechanism of hypertrophic scar fibroblasts (HSFb), we constructed lentiviral vectors that either overexpressed TLP or encoded smallmore » hairpin RNAs (shRNAs) targeting TLP, then we transfected them into HSFb. TLP knockdown in HSFb resulted in reduced levels of cell contraction, type I and type III collagen mRNA transcripts and protein expression, and higher levels of fibronectin (FN) compared to control groups. In addition, knockdown of TLP promoted the phosphorylation of Smad3 but repressed Smad2 and Erk-1/2 phosphorylation in human hypertrophic scar fibroblasts compared to control groups. The reduction of TLP did not interfere with HSF proliferative ability, but exogenous TLP cooperated with TGF-β1 to increase cell viability. Together, our findings demonstrate evidence for a contribution of TLP expression in hypertrophic scar formation and contraction. - Highlights: • TLP acted different roles in the activating of Smad2- and Smad3-dependent signaling. • TLP may induce TGF-β1-mediated collagens expression through Smad signalings and MAPK signaling. • TLP may enhance HSFb contraction by increasing the expression of α-SMA. • Exogenous TLP can cooperate with TGF-β1 to increase cell viability.« less

Reduction of post-surgical scarring with the use of ablative fractional CO2 lasers: A pilot study using a porcine model.

PubMed

Baca, Marissa E; Neaman, Keith C; Rapp, Derek A; Burton, Michael E; Mann, Robert J; Renucci, John D

2017-01-01

Wound healing inevitably leads to scarring, which leads to functional and cosmetic defects. It is the goal of this study to investigate the immediate use of ablative fractional CO 2 lasers to reduce post-operative scarring secondary to surgical wounds. In this prospective controlled study, 20 surgical incisions were created on each of three pigs. Fifteen of the incisions were treated with an ablative fractional CO 2 laser at one of three laser settings. The remaining five incisions served as a control. Punch biopsies were taken post-operatively over time. Digital photographs were taken of each incisional scar at each time period. Blinded evaluators used a previously verified scoring system to score photographs of the incisional scars taken at the 6 month time period. With regards to the comparison between the three individual laser treatment groups and the control, there were no statistically significant effects for treatment (P = 0.40), time (P = 0.48), or for the interaction of time and treatment (P = 0.57). With regards to the visual assessment tool, there were no statistically significant differences between treatments for Overall Appearance (P = 0.21) or for Total Score (P = 0.24). In the limited setting of this pilot study, treatment of surgical incisions with ablative fractional CO 2 lasers does not significantly lessen scar formation. In addition, photographic analysis was not able to demonstrate a significant difference. Future studies on this topic will need a larger sample size to better answer whether a statistically significant difference may exist. Lasers Surg. Med. 49:122-128, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Scarless wound healing: finding the right cells and signals.

PubMed

Leavitt, Tripp; Hu, Michael S; Marshall, Clement D; Barnes, Leandra A; Lorenz, H Peter; Longaker, Michael T

2016-09-01

From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal adhesion kinase).

A new argon gas-based device for the treatment of keloid scars with the use of intralesional cryotherapy.

PubMed

van Leeuwen, Michiel C E; Bulstra, Anne-Eva J; van Leeuwen, Paul A M; Niessen, Frank B

2014-12-01

Intralesional (IL) cryotherapy is a new promising technique for the treatment of keloid scars, in which the scar is frozen from inside. Multiple devices are available, mostly based on a simple liquid nitrogen Dewar system, which have a limited freezing capacity. Argon gas-based systems ensure accurate and highly controlled freezing and have shown to be effective within the field of oncologic surgery. However, this technique has never been used for the treatment of keloid scars. This prospective study evaluates an argon gas-based system for the treatment of keloids in a patient population including all Fitzpatrick skin types with a 1-year follow-up. Twenty-five patients with 30 keloid scars were included and treated with a device called Seednet (Galil Medical, Yokneam, Israel). Scar quality and possible scar recurrence were assessed before treatment and post treatment (6 and 12 months) with objective devices determining scar color, scar elasticity, scar volume, and patient's skin type. In addition, scars were evaluated using the Patient and Observer Scar Assessment Scale. After 12 months, a significant volume reduction of 62% was obtained, p = 0.05. Moreover, complaints of pain and itching were alleviated and scar quality had improved according to the Patient and Observer Scar Assessment Scale. Scar pigmentation recovered in 62% of all keloid scars within 12 months. Five out of 30 (17%) scars recurred within 12 months, three of which had previously been treated with liquid nitrogen-based IL cryotherapy. Both recurrent and persistent hypopigmentation were mainly seen in Afro-American patients. IL cryotherapy with the use of an argon gas-based system proves to be effective in the treatment of keloid scars, yielding volume reduction and low recurrence rates. Although hypopigmentation recovered in most cases, it is strongly related to non-Caucasian patients. Finally, additional treatment of keloid scars previously unresponsive to IL cryotherapy is predisposed to a high recurrence rate. NCT02063243. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Acne Scarring—Pathogenesis, Evaluation, and Treatment Options

PubMed Central

Connolly, Deirdre; Vu, Ha Linh; Mariwalla, Kavita

2017-01-01

Acne vulgaris is a ubiquitous problem affecting 80 percent of people ages 11 to 30 years, with many patients experiencing some degree of scarring. This review focuses on atrophic scars, the most common type of acne scar. We briefly address the cellular sequelae that lead to scar formation and the initial evaluation of patients with acne scars. We then discuss an algorithmic approach to the treatment of acne scarring based on the classification of scars into erythematous and atrophic types. Lastly, we discuss the future treatment of acne scars and ongoing clinical trials. PMID:29344322

Two-dimensional strain echocardiography technology for evaluation of myocardial strain in swimming athletes after high-intensity exercise.

PubMed

Liang, Chen; Ma, Yun; Gao, Can; Zhang, Jianhong; Yang, Min; Chen, Gen; Fu, Shan; Zhu, Tiangang

2017-02-01

The aim of this study was to investigate the change in myocardial strain in swimming athletes before and after high-intensity exercise using two-dimensional strain echocardiography (2DSE) technology. To assess whether the local and overall myocardial function and myocardial injury are accurately measured using 2DSE technology, 15 swimming athletes were selected as research objects. We applied 2DSE technology to track the 2D ultrasound images of the apical four chambers, the apical two chambers, and the apical long axis before and after high-intensity, increasing-load exercise. We recorded indices such as the left ventricular global strain (GS) and the left ventricular segmental wall longitudinal peak systolic strain (PS) in 18 systoles and analyzed the myocardial strain change before and after exercise. After high-intensity exercise, the overall myocardial strain decreased, especially the strain of the posterior wall, posterior divider, lateral wall, lower wall, and the basal and middle segments of the anterior wall. The influence of exercise on myocardial strain was greater on the basal and middle segments than on the apical segment. One-time intensive exercise negatively affected the myocardial muscle. Myocardial muscles in the apical segment and the myocardial wall were more sensitive to intensive exercise. The 2DSE technology can precisely position the motion-sensitive areas and help locate myocardial injury. © 2017, Wiley Periodicals, Inc.

Pleiotrophin is downregulated in human keloids.

PubMed

Lee, Dong Hun; Jin, Cheng Long; Kim, Yeji; Shin, Mi Hee; Kim, Ji Eun; Kim, Minji; Lee, Min Jung; Cho, Soyun

2016-10-01

Keloid is an abnormal hyperproliferative scarring process with involvement of complex genetic and triggering environmental factors. Previously published dysregulated gene expression profile of keloids includes genes involved in tumor formation. Pleiotrophin (PTN) is a secreted, heparin-binding growth factor which is involved in various biological functions such as cell growth, differentiation, and tumor progression. Although PTN expression was reported to be increased in hypertrophic scars, there is no study on PTN expression in keloids, and previous microarray results are controversial. To clarify differential expression of PTN in keloids, we investigated the expression of PTN and its interacting molecules in keloid and control fibroblasts, and performed immunohistochemical staining of PTN using tissue arrays. The expressions of PTN, its upstream regulator platelet-derived growth factor subunit B (PDGF-B) and corresponding PDGF receptors were significantly downregulated in keloid fibroblasts compared to normal human fibroblasts, and the decreased PTN protein expression was confirmed by immunohistochemistry as well as Western blot. Moreover, functional downstream receptor protein tyrosine phosphatase β/ζ was significantly upregulated in keloid fibroblasts, supporting overall downregulation of PTN signaling pathway. The lowered PTN expression in keloids suggests a different pathomechanism from that of hypertrophic scars.

Role of cardiomyocyte circadian clock in myocardial metabolic adaptation

USDA-ARS?s Scientific Manuscript database

Marked circadian rhythmicities in cardiovascular physiology and pathophysiology exist. The cardiomyocyte circadian clock has recently been linked to circadian rhythms in myocardial gene expression, metabolism, and contractile function. For instance, the cardiomyocyte circadian clock is essential f...

Sense of coherence--a determinant of quality of life over time in older female acute myocardial infarction survivors.

PubMed

Norekvål, Tone M; Fridlund, Bengt; Moons, Philip; Nordrehaug, Jan E; Saevareid, Hans I; Wentzel-Larsen, Tore; Hanestad, Berit R

2010-03-01

To determine the relationships between different sense of coherence levels and quality of life, and in older female myocardial infarction survivors; to investigate how socio-demographic, clinical characteristics, sense of coherence self-reported symptoms and function affect quality of life; and to determine whether sense of coherence and quality of life are stable during a six-month follow-up. Myocardial infraction confers new physical and mental challenges. However, research on sense of coherence and other factors involved in maintaining physical, psychosocial and environmental aspects of quality of life in older female myocardial infraction survivors is scant. Survey. A postal survey was conducted of 145 women, aged 62-80 years, three months to five years after myocardial infarction (T1), with a follow-up after six months (T2). Self-reported socio-demographic and clinical data and hospital medical records data were collected. The sense of coherence scale (SOC-29) and the World Health Organization Quality of Life Instrument Abbreviated (WHOQOL-BREF) were used. We found a significant difference in quality of life between weak, moderate, and strong sense of coherence groups (p<0.001). Sense of coherence contributed to the level of all quality of life domains (p<0.001). Several clinical characteristics contributed to quality of life: (1) physical domain: comorbidities (p<0.001), previous myocardial infarction (p = 0.013), ejection fraction (p<0.011), length of hospital stay (p = 0.005) symptoms and function (p<0.001); (2) psychological domain: previous myocardial infarction (p = 0.031) and symptoms and function (p<0.001); and (3) environmental domain: education (p = 0.033) and symptoms and function (p = 0.003). On group level, both sense of coherence and quality of life were stable. Experiencing specific health changes (p<0.001), not major life events, influenced quality of life during the six-month follow-up. Sense of coherence was an important stable determinant of quality of life domains in female myocardial infarction survivors. Although other factors were identified, further research is needed to elucidate additional determinants of quality of life. These specific factors could guide clinicians in making treatment decisions that optimize the quality of life of their patients. Applying a salutogenic perspective through patient education may be important.

Skin, fascias, and scars: symptoms and systemic connections

PubMed Central

Bordoni, Bruno; Zanier, Emiliano

2014-01-01

Every element or cell in the human body produces substances that communicate and respond in an autocrine or paracrine mode, consequently affecting organs and structures that are seemingly far from each other. The same also applies to the skin. In fact, when the integrity of the skin has been altered, or when its healing process is disturbed, it becomes a source of symptoms that are not merely cutaneous. The skin is an organ, and similar to any other structure, it has different functions in addition to connections with the central and peripheral nervous system. This article examines pathological responses produced by scars, analyzing definitions and differences. At the same time, it considers the subcutaneous fascias, as this connective structure is altered when there is a discontinuous cutaneous surface. The consequence is an ample symptomatology, which is not limited to the body area where the scar is located, such as a postural or trigeminal disorder. PMID:24403836

Quantum scar and breakdown of universality in graphene: A theoretical insight

NASA Astrophysics Data System (ADS)

Iyakutti, Kombiah; Rajeswarapalanichamy, Ratnavelu; Surya, Velappa Jayaraman; Kawazoe, Yoshiyuki

2017-12-01

Graphene has brought forward a lot of new physics. One of them is the emergence of massless Dirac fermions in addition to the electrons and these features are new to physics. In this theoretical study, the signatures for quantum scar and the breakdown of universality in graphene are investigated with reference to the presence of these two types of fermions. Taking the graphene quantum dot (QD) potential as the confining potential, the radial part of Dirac equations are solved numerically. Concentrations of the two component eigen-wavefunctions about classical periodic orbits emerge as the signatures for the quantum scar. The sudden variations, in the ratio of the radial wave-functions (large and small components), R(g/f), with mass ratio κ are the signatures for breakdown of universality in graphene. The breakdown of universality occurs for the states k = -1 and k = 1, and the state k = -1 is more susceptible to the breakdown of universality.

Ultrasound assessed thickness of burn scars in association with laser Doppler imaging determined depth of burns in paediatric patients.

PubMed

Wang, Xue-Qing; Mill, Julie; Kravchuk, Olena; Kimble, Roy M

2010-12-01

This study describes the ultrasound assessment of burn scars in paediatric patients and the association of these scar thickness with laser Doppler imaging (LDI) determined burn depth. A total of 60 ultrasound scar assessments were conducted on 33 scars from 21 paediatric burn patients at 3, 6 and 9 months after-burn. The mean of peak scar thickness was 0.39±0.032 cm, with the thickest at 6 months (0.40±0.036 cm). There were 17 scald burn scars (0.34±0.045 cm), 4 contact burn scars (0.61±0.092 cm), and 10 flame burn scars (0.42±0.058 cm). Each group of scars followed normal distributions. Twenty-three scars had original burns successfully scanned by LDI and various depths of burns were presented by different colours according to blood perfusion units (PU), with dark blue <125, light blue 125-250, and green 250-440 PU. The thickness of these scars was significantly different between the predominant colours of burns, with the thinnest scars for green coloured burns and the thickest for dark blue coloured burns. Within light blue burns, grafted burns healed with significantly thinner scars than non-grafted burns. This study indicates that LDI can be used for predicting the risk of hypertrophic scarring and for guiding burn care. To our knowledge, this is the first study to correlate the thickness of burns scars by ultrasound scan with burn depth determined by LDI. Copyright © 2010 Elsevier Ltd and ISBI. All rights reserved.

Imaging Collagen in Scar Tissue: Developments in Second Harmonic Generation Microscopy for Biomedical Applications

PubMed Central

Mostaço-Guidolin, Leila; Rosin, Nicole L.; Hackett, Tillie-Louise

2017-01-01

The ability to respond to injury with tissue repair is a fundamental property of all multicellular organisms. The extracellular matrix (ECM), composed of fibrillar collagens as well as a number of other components is dis-regulated during repair in many organs. In many tissues, scaring results when the balance is lost between ECM synthesis and degradation. Investigating what disrupts this balance and what effect this can have on tissue function remains an active area of research. Recent advances in the imaging of fibrillar collagen using second harmonic generation (SHG) imaging have proven useful in enhancing our understanding of the supramolecular changes that occur during scar formation and disease progression. Here, we review the physical properties of SHG, and the current nonlinear optical microscopy imaging (NLOM) systems that are used for SHG imaging. We provide an extensive review of studies that have used SHG in skin, lung, cardiovascular, tendon and ligaments, and eye tissue to understand alterations in fibrillar collagens in scar tissue. Lastly, we review the current methods of image analysis that are used to extract important information about the role of fibrillar collagens in scar formation. PMID:28809791

[Establishment of a keloid model by transplanting human keloid onto the backs of nude mice].

PubMed

Philandrianos, C; Gonnelli, D; Andrac-Meyer, L; Bruno, M; Magalon, G; Mordon, S

2014-08-01

Keloid scar is a proliferative healing dysfunction formed by an excessive build-up of collagen fibers on the dermis. It is responsible of aesthetic and functional disabilities. There is no ideal treatment and recurrence occurs very often. Keloid scars occur only to human, that's why animal model needs to be made to study this pathology and new treatments. Few models have been described using human keloid scars implanted into subcutaneous tissue of nude mice or rat. To allow study of topical and laser treatment we have developed a new animal model using human keloid scar fragment with epidermal and dermal tissue implanted into back of nude mice like a full thickness skin graft. Keloid fragments from five donors have been grafted onto 40 nudes mice. Macroscopic and microscopic studies have been made at day 28, 56, 84 and 112. We observed integration of the fragments in all cases. Hyalinized collagen bundles were observed in all implant biopsies confirming the stability of the keloid architecture within 112 days. This model is easily reproducible and allows the study of topical treatment and laser due to the accessibility of the keloid. Copyright © 2012. Published by Elsevier Masson SAS.

Acute myocardial infarction with changing axis deviation.

PubMed

Patanè, Salvatore; Marte, Filippo

2011-07-01

Changing axis deviation has been rarely reported also during atrial fibrillation or atrial flutter. Changing axis deviation has been rarely reported also during acute myocardial infarction associated with atrial fibrillation. Isolated left posterior hemiblock is a very rare finding but the evidence of transient right axis deviation with a left posterior hemiblock pattern has been reported during acute anterior myocardial infarction as related with significant right coronary artery obstruction and collateral circulation between the left coronary system and the posterior descending artery. Left anterior hemiblock development during acute inferior myocardial infarction can be an indicator of left anterior descending coronary artery lesions, multivessel coronary artery disease, and impaired left ventricular systolic function. We present a case of changing axis deviation in a 62-year-old Italian man with acute myocardial infarction. Also this case focuses attention on changing axis deviation during acute myocardial infarction. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Overexpression of Hsp20 Prevents Endotoxin-Induced Myocardial Dysfunction and Apoptosis via Inhibition of NF-κB Activation

PubMed Central

Wang, Xiaohong; Zingarelli, Basilia; Connor, Michael O’; Zhang, Pengyuan; Adeyemo, Adeola; Kranias, Evangelia G.; Wang, Yigang; Fan, Guo-Chang

2009-01-01

The occurrence of cardiovascular dysfunction in sepsis is associated with a significantly increased mortality rate of 70% to 90% compared with 20% in septic patients without cardiovascular impairment. Thus, rectification or blockade of myocardial depressant factors should partly ameliorate sepsis progression. Heat shock protein 20 (Hsp20) has been shown to enhance myocardial contractile function and protect against doxorubicin-induced cardiotoxicity. To investigate the possible role of Hsp20 in sepsis-mediated cardiac injury, we first examined the expression profiles of five major Hsps in response to lipopolysaccharide (LPS) challenge, and observed that only the expression of Hsp20 was downregulated in LPS-treated myocardium, suggesting that this decrease might be one of mechanisms contributing to LPS-induced cardiovascular defects. Further studies using loss-of-function and gain-of function approaches in adult rat cardiomyocytes verified that reduced Hsp20 levels were indeed correlated with the impaired contractile function. In fact, overexpression of Hsp20 significantly enhanced cardiomyocyte contractility upon LPS treatment. Moreover, after administration of LPS (25μg/g) in vivo, Hsp20 transgenic mice (10-fold overexpression) displayed: 1) an improvement in myocardial function; 2) reduced the degree of cardiac apoptosis; and 3) decreased NF-κB activity, accompanied with reduced myocardial cytokines IL-1β and TNF-α production, compared to the LPS-treated non-transgenic littermate controls. Thus, the increases in Hsp20 levels can protect against LPS-induced cardiac apoptosis and dysfunction, associated with inhibition of NF-κB activity, suggesting that Hsp20 may be a new therapeutic agent for the treatment of sepsis. PMID:19501592

Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis.

PubMed

Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdélyi, Katalin; Holovac, Eileen; Liaudet, Lucas; Lee, Wen-Shin; Haskó, György; Mechoulam, Raphael; Pacher, Pál

2015-01-06

Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX's cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury.

Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis

PubMed Central

Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdélyi, Katalin; Holovac, Eileen; Liaudet, Lucas; Lee, Wen-Shin; Haskó, György; Mechoulam, Raphael; Pacher, Pál

2015-01-01

Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX’s cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury. PMID:25569804

Remote ischemic preconditioning and endothelial function in patients with acute myocardial infarction and primary PCI.

PubMed

Manchurov, Vladimir; Ryazankina, Nadezda; Khmara, Tatyana; Skrypnik, Dmitry; Reztsov, Roman; Vasilieva, Elena; Shpektor, Alexander

2014-07-01

Remote ischemic preconditioning by transient limb ischemia reduces myocardial ischemia-reperfusion injury in patients undergoing percutaneous coronary intervention. The aim of the study we report here was to assess the effect of remote ischemic preconditioning on endothelial function in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. Forty-eight patients with acute myocardial infarction were enrolled. All participants were randomly divided into 2 groups. In Group I (n = 23), remote ischemic preconditioning was performed before primary percutaneous coronary intervention (intermittent arm ischemia-reperfusion through 4 cycles of 5-minute inflation and 5-minute deflation of a blood-pressure cuff to 200 mm Hg). In Group II (n = 25), standard percutaneous coronary intervention without preconditioning was performed. We assessed endothelial function using the flow-mediated dilation test on baseline, then within 1-3 hours after percutaneous coronary intervention, and again on days 2 and 7 after percutaneous coronary intervention. The brachial artery flow-mediated dilation results were significantly higher on the first day after primary percutaneous coronary intervention in the preconditioning group (Group I) than in the control group (Group II) (12.1% vs 0.0%, P = .03, and 11.1% vs 6.3%, P = .016, respectively), and this difference remained on the seventh day (12.3% vs 7.4%, P = .0005, respectively). We demonstrated for the first time that remote ischemic preconditioning before primary percutaneous coronary intervention significantly improves endothelial function in patients with acute myocardial infarction, and this effect remains constant for at least a week. We suppose that the improvement of endothelial function may be one of the possible explanations of the effect of remote ischemic preconditioning. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantification of functional results after facial burns by the faciometer.

PubMed

Koller, R; Kargül, G; Giovanoli, P; Meissl, G; Frey, M

2000-12-01

In the present study the faciometer(R) is introduced in order to quantify the ranges of mimic movements observed after surgical treatment of facial burns. This instrument which consists of calipers and an electronic display was introduced in 1994 in order to measure the extent of facial palsy during reconstructive procedures. The study group consisted of 23 patients, who had been operated on for facial burns. The distances between standardised stable and moving points in the face were determined after mimic movements such as lifting of the eyebrows, maximum showing of the teeth and pursing of the lips. These distances were expressed as a percentage of the distance at rest. For comparison the scars were classified according to the Vancouver Scar Scale. In all patients the functional results after burn trauma in the face and, in some cases, asymmetries at rest could be objectified. Depending upon the severity of scarring, the distance between tragus and mouth was shortened between 0 and 19% after maximal showing of the teeth. In general the mouth region showed more functional deficits than the forehead. Comparing different manners of treatment, it could be objectively demonstrated that the results after deep burns requiring skin grafts were worse than those observed after more superficial lesions and other methods of coverage. The application of keratinocytes to close the burn showed highly variable results.

Incremental value of normal adenosine perfusion cardiac magnetic resonance: Long-term outcome.

PubMed

Sozzi, Fabiola B; Iacuzio, Laura; Civaia, Filippo; Canetta, Ciro; Berthier, Frederic; Rusek, Stephane; Rossi, Philippe; Lombardi, Federico; Dreyfus, Gilles; Dor, Vincent

2015-06-01

The purpose of the study was to determine the long-term prognostic value of normal adenosine stress cardiac magnetic resonance imaging (CMR) in patients referred for evaluation of myocardial ischemia. We reviewed 300 consecutive patients (age 65 ± 11 years, 74% male) with suspected or known coronary disease and normal wall motion who had undergone adenosine stress CMR negative for ischemia and scar. Most patients were at intermediate risk of coronary artery disease. The end points studied were all causes of mortality and major adverse cardiac events, including cardiac death, myocardial infarction, revascularization, and hospitalization for unstable angina. During a mean follow-up of 5.5 years (mean = 5.4 ± 1.1), 16 patients died because of various causes (cardiac death in 5 patients). Three patients had a nonfatal myocardial infarction, 7 patients were hospitalized for revascularization, and 11 were medically treated for unstable angina. The annual cardiac event rate was 1.3% (0.78% in the first 3 years and 1.9% between the fourth and sixth years). The predictors of major adverse cardiac events in a multivariate analysis model were as follows: advanced age (hazard ratio [HR] 1.15, 95% confidence interval [95% CI] 1.02-1.30), diabetes (HR 17.5, 95% CI 2.2-140), and the habit of smoking (HR 5.9, 95% CI 1.0-35.5). For all causes of mortality, the only predictor was diabetes (HR 11.4, 95% CI 1.76-74.2). Patients with normal stress CMR had an excellent outcome during the 3 years after the study. The cardiac event rate was higher between the fourth and sixth years. Over a 5.5-year period, a low event rate and excellent prognosis occurred in patients with normal adenosine stress CMR. Low- to intermediate-risk patients with a normal CMR are at low risk for subsequent cardiac events. Copyright © 2015 Elsevier Inc. All rights reserved.

Physical activity and sudden cardiac death in elders--a Croatian study.

PubMed

Duraković, Zijad; Duraković, Marjeta Misigoj; Skavić, Josip; Gojanović, Marija Definis

2011-03-01

The paper deals with the sudden cardiac death in elders due to physical activity in Croatia and to compare it to other population groups who practice physical activity. The data are a part of a retrospective study dealing with 59 sudden death due to physical activity in men in Croatia: from January 1, 1988 to December 31, 2008. Fifteen aged 65 to 82 years were recreationally engaged in physical activity: six in swimming, four in tennis, one in driving a bicycle, one in jogging, two in bowling and one died during sexual act. Only one had symptoms of pectoral angina, two suffered from arterial hypertension, and two had congestive heart failure. Eleven were without symptoms before exercise. At forensic autopsy, fourteen had coronary heart disease, seven had critical coronary artery stenosis, three had occluded left descendens anterior coronary artery and four critical coronary stenosis, four had a recent myocardial infarctions, and eleven had myocardial scars due to previous myocardial infarctions. Twelve of them had left ventricular hypertrophy: 15-25 mm. In Croatia, about 7per cent of the entire male population undertake recreational physical activity, while 13 per cent of them are elders. A sudden cardiac death due to recreational physical activity in elders reached 1.71/100 000 yearly, in the entire male population engaged in recreational physical exercise: 0.75/100 000 (p = 0.05730), in the total male population aged 15-40 engaged in sports and recreational physical exercise: 0.57/100.0000 (p = 0.00387), in young athletes: 0.15/100 000 (p = 0.00000). Medical examination of all elderly persons has to be done before starting of recreational physical activity: by clinical examination, searching for risk factors for atherosclerosis, performing ECG at rest, stress ECG, and echocardiography and to repeat the medical examination at least once a year Physical activity should start with a warm-up period and with a gradually increasing load, and usually not to exceed 6-7 metabolic equivalents (METs).

Early reduced myocardial diastolic function in children and adolescents with type 1 diabetes mellitus a population-based study.

PubMed

Brunvand, Leif; Fugelseth, Drude; Stensaeth, Knut Håkon; Dahl-Jørgensen, Knut; Margeirsdottir, Hanna Dis

2016-05-25

Reduced diastolic myocardial function is an early sign of diabetic cardiomyopathy. The aim of this study was to test the hypothesis that children and adolescents with type 1 diabetes mellitus (T1D), but without other known complications, have early reduced diastolic myocardial function diagnosed with echocardiographic color tissue Doppler imaging (cTDI). cTDI examination was carried out in 173 T1D patients and 62 age-matched controls. The T1D-patients were 8-18 years old with (mean (SD)) diabetes duration of 5.6 (3.4) years and HbA1c of 8.4 (1.3). All were treated with either insulin pumps or 4-6 daily insulin injections. cTDI early (E') and late (A') peak diastolic velocities and systolic peak velocity were measured from the lateral, septal, anterior and posterior mitral annulus and from the lateral tricuspidal annulus. Myocardial diastolic function was reduced in the T1D-patients with higher peak A'-velocity and lower E'/A'-ratio in all registrations. Overall mean (SD) mitral E'/A'-ratio was 2.3 (0.5) in T1D and 2.7 (0.6) in the controls (p < 0001). The overall mitral E'/A'-ratio was negative associated with blood pressure (BP) and body mass index (BMI). Stratifying all participants into three groups according to BMI (<25, 25-75, >75 centile, respectively), the T1D had lower E'/A'-values in all stratified groups, except for in the highest BMI-group where both T1D and controls had the lowest E'/A'-ratio. Systolic function did not differ in any of the measurements. There were no associations with sex, diabetes duration, carotid artery intima-media-thickness, vessel elasticity or HbA1c. Diabetic children and adolescents using modern intensive insulin treatment had echocardiographic signs of reduced diastolic myocardial function despite short duration of disease. The reduced function was associated with higher BP and higher BMI.

Injection of human mesenchymal stem cells improves healing of vocal folds after scar excision--a xenograft analysis.

PubMed

Svensson, Bengt; Nagubothu, Srinivasa R; Cedervall, Jessica; Chan, Roger W; Le Blanc, Katrina; Kimura, Miwako; Ährlund-Richter, Lars; Tolf, Anna; Hertegård, Stellan

2011-10-01

Using a xenograft model the aim was to analyze if injection of human mesenchymal stem cells (hMSC) into the rabbit vocal fold (VF), after excision of an established scar, can improve the functional healing of the VF. Prospective design with an experimental xenograft model. The VFs of 12 New Zealand rabbits were injured by a bilateral localized resection. After 9 weeks the scar after the resection was excised and hMSC were injected into the VFs. After another 10 weeks 10 VFs were dissected and stained for histology. Lamina propria thickness and relative content of collagen type I were measured. Viscoelasticity of 14 VFs at phonatory frequencies was quantified by a simple-shear rheometer. The hMSC survival was determined using a human DNA specific reference probe, that is, FISH analysis. The viscoelastic measurements, that is, dynamic viscosity and elastic shear modulus for the hMSC-treated VFs, were found to be similar to those of normal controls and were significantly lower than those of untreated controls (P < .05). A significant reduction in lamina propria thickness was also shown for the hMSC treated VFs compared with the untreated VFs (P < .05). This histologic finding corresponded with the viscoelastic results. No hMSC survived 10 weeks after the injection. Human mesenchymal stem cells injected into the rabbit VF following the excision of a chronic scar, were found to enhance the functional healing of the VF with reduced lamina propria thickness and restored viscoelastic shear properties. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Optimal placement of a brachioplasty scar: a survey evaluation.

PubMed

Samra, Salem; Samra, Fares; Liu, Yuen-Jong; Sawh-Martinez, Rajendra; Persing, John

2013-10-01

Brachioplasty has become a popular procedure to rejuvenate the upper arm, with its frequency increasing proportionately to the popularity of surgical weight loss procedures. The major complication of the procedure is undesirable, visible scarring. An ongoing, unresolved debate in the brachioplasty literature is the optimal placement of the brachioplasty scar. Some authors advocate a medially based incision along the bicipital groove, whereas others prefer to leave the scar posteriorly in the brachial sulcus. In addition, some advocate a sinusoidal scar over a straight-line closure. This study attempts to resolve the question of where and how to place the scar based on population surveys. Photographs were taken of a model with her arm progressively abducted at the shoulder to a level of 90 degrees, with the elbow progressively flexed to 90 degrees and the arm externally rotated. Anterior and posterior views were included. Using Photoshop, a brachioplasty scar was digitally created and placed on the arm first medially in the bicipital groove, then posteriorly in the brachial sulcus. Straight-line scars and sinusoidal scars were also compared in each position. Before creating a computer-generated image of the scars, the scar lines were marked with a marking pen to ensure they could be followed with movement of the model's arm. An online survey was then created and distributed and included multiple variables: position of the scar, length of scar vs residual deformity, and acceptability based on phase of scar in time (early vs late result). The scale was numerical from 1 to 5, with 1 being a very objectionable scar and 5 being a very acceptable scar. The survey was disseminated among the general public, plastic surgeons, and patients in the Yale Cosmetic Surgery Resident Clinic who were either seen in consultation for brachioplasty or who underwent the procedure. Electronic surveys were distributed to and completed by the general public (n = 117), local plastic surgery residents and attendings (n = 10), and patients who had undergone or were seen in consultation for brachioplasty (n = 9). Among all participants, in the chronic phase, a medial straight scar received an average rating of 4.00, a posterior straight scar received an average rating of 3.14, a posterior sinusoidal scar received an average rating of 2.61, and a medial sinusoidal scar received an average rating of 2.03. Across age groups, gender, plastic surgeons, and patients, the medially based straight brachioplasty scar is more acceptable than the posteriorly based straight scar (4.00 vs 3.14, P < 0.001). If the scar shape is made sinusoidal, a posteriorly based scar is favored over a medial one (2.61 vs 2.03, P < 0.001), yet this is still not as aesthetically pleasing as a medial straight scar (4.00 vs 2.61, P < 0.001). Furthermore, survey participants accepted a longer scar over a residual deformity (58.8% vs 41.2%). Based on the preferences of the populations surveyed, we conclude that the medially based straight scar is the most aesthetically acceptable option when performing a brachioplasty.

Comparison of usefulness of N-terminal pro-brain natriuretic peptide as an independent predictor of cardiac function among admission cardiac serum biomarkers in patients with anterior wall versus nonanterior wall ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Haeck, Joost D E; Verouden, Niels J W; Kuijt, Wichert J; Koch, Karel T; Van Straalen, Jan P; Fischer, Johan; Groenink, Maarten; Bilodeau, Luc; Tijssen, Jan G P; Krucoff, Mitchell W; De Winter, Robbert J

2010-04-15

The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction. The NT-pro-BNP levels were divided into quartiles and correlated with left ventricular function and infarct size measured by CMR imaging at 4 to 6 months. Compared to the lower quartiles, patients with nonanterior wall myocardial infarction in the highest quartile of NT-pro-BNP (> or = 260 pg/ml) more often had a greater left ventricular end-systolic volume (68 vs 39 ml/m(2), p <0.001), a lower left ventricular ejection fraction (42% vs 54%, p <0.001), a larger infarct size (9 vs 4 g/m(2), p = 0.002), and a larger number of transmural segments (11% of segments vs 3% of segments, p <0.001). Multivariate analysis revealed that a NT-pro-BNP level of > or = 260 pg/ml was the strongest independent predictor of left ventricular ejection fraction in patients with nonanterior wall myocardial infarction compared to the other serum biomarkers (beta = -5.8; p = 0.019). In conclusion, in patients with nonanterior wall myocardial infarction undergoing primary percutaneous coronary intervention, an admission NT-pro-BNP level of > or = 260 pg/ml was a strong, independent predictor of left ventricular function assessed by CMR imaging at follow-up. Our findings suggest that NT-pro-BNP, a widely available biomarker, might be helpful in the early risk stratification of patients with nonanterior wall myocardial infarction. Copyright 2010 Elsevier Inc. All rights reserved.

Deficiency of Rac1 Blocks NADPH Oxidase Activation, Inhibits Endoplasmic Reticulum Stress, and Reduces Myocardial Remodeling in a Mouse Model of Type 1 Diabetes

PubMed Central

Li, Jianmin; Zhu, Huaqing; Shen, E; Wan, Li; Arnold, J. Malcolm O.; Peng, Tianqing

2010-01-01

OBJECTIVE Our recent study demonstrated that Rac1 and NADPH oxidase activation contributes to cardiomyocyte apoptosis in short-term diabetes. This study was undertaken to investigate if disruption of Rac1 and inhibition of NADPH oxidase would prevent myocardial remodeling in chronic diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced by injection of streptozotocin in mice with cardiomyocyte-specific Rac1 knockout and their wild-type littermates. In a separate experiment, wild-type diabetic mice were treated with vehicle or apocynin in drinking water. Myocardial hypertrophy, fibrosis, endoplasmic reticulum (ER) stress, inflammatory response, and myocardial function were investigated after 2 months of diabetes. Isolated adult rat cardiomyocytes were cultured and stimulated with high glucose. RESULTS In diabetic hearts, NADPH oxidase activation, its subunits' expression, and reactive oxygen species production were inhibited by Rac1 knockout or apocynin treatment. Myocardial collagen deposition and cardiomyocyte cross-sectional areas were significantly increased in diabetic mice, which were accompanied by elevated expression of pro-fibrotic genes and hypertrophic genes. Deficiency of Rac1 or apocynin administration reduced myocardial fibrosis and hypertrophy, resulting in improved myocardial function. These effects were associated with a normalization of ER stress markers' expression and inflammatory response in diabetic hearts. In cultured cardiomyocytes, high glucose–induced ER stress was inhibited by blocking Rac1 or NADPH oxidase. CONCLUSIONS Rac1 via NADPH oxidase activation induces myocardial remodeling and dysfunction in diabetic mice. The role of Rac1 signaling may be associated with ER stress and inflammation. Thus, targeting inhibition of Rac1 and NADPH oxidase may be a therapeutic approach for diabetic cardiomyopathy. PMID:20522592

Hypothyroidism-induced myocardial damage and heart failure: an overlooked entity.

PubMed

Shuvy, Mony; Shifman, Oshrat E Tayer; Nusair, Samir; Pappo, Orit; Lotan, Chaim

2009-01-01

Hypothyroid state may induce cardiac muscle impairment such as diastolic dysfunction and abnormal relaxation time. Advanced heart failure in hypothyroid patients has been described only in severe symptomatic cases, mostly during myxedematous coma. We describe an unusual case of asymptomatic patient with hypothyroidism who presented with severely reduced cardiac function with elevated cardiac enzymes reflecting significant myocardial injury. Comprehensive evaluation for heart failure was suggestive only for long-standing untreated hypothyroidism. Endomyocadial biopsy demonstrated unique histological findings of mucopolysaccharide accumulation attributed to hypothyroid state. Asymptomatic hypothyroidism may cause severe reduction in cardiac function accompanied with elevated cardiac enzymes. To our knowledge, this is the first description of human myocardial biopsy revealing mucopolysaccharide accumulation attributed to hypothyroid state.

New radionuclide agents for cardiac imaging: Description and application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kahn, J.K.; Pippin, J.J.; Corbett, J.R.

1989-08-01

The introduction of three new radiopharmaceuticals into clinical research and practice has broadened the potential applications and scope of nuclear cardiology examinations. Technetium-99m labeled isonitrile perfusion agents have excellent imaging characteristics allowing the accurate identification of coronary artery disease. Simultaneous assessments of ventricular function are possible with these agents. Iodine-123 phenylpentadecanoic acid myocardial scintigraphy permits assessments of myocardial perfusion and fatty acid metabolism, and permits investigations of myocardial metabolism with conventional imaging equipment. Iodine-123 meta-iodobenzyl-guanidine serves as an indicator of the functional integrity of the sympathetic nervous system and permits evaluations of the effects of various disease states on catecholaminemore » handling by the heart. 58 references.« less

A practical and objective approach to scar colour assessment.

PubMed

Hallam, M J; McNaught, K; Thomas, A N; Nduka, C

2013-10-01

Scarring is a significant clinical problem following dermal injury. However, scars are not a single describable entity and huge phenotypic variability is evident. Quantitative, reproducible inter-observer scar assessment is essential to monitor wound healing and the effect of scar treatments. Scar colour, reflecting the biological processes occurring within a scar, is integral to any assessment. The objective of this study was to analyse scar colour using the non-invasive Eykona® Wound Measurement System (the System) as compared against the Manchester Scar Scale (MSS). Three dimensional images of 43 surgical scars were acquired post-operatively from 35 patients at 3-6 months and the colour difference between the scar and surrounding skin was calculated (giving ΔLab values). The colourimetric results were then compared against subjective MSS gradings. A significant difference in ΔLab values between MSS gradings of "slight mismatch" and "obvious mismatch" (p<0.025) and between "obvious mismatch" and "gross mismatch" (p<0.05) were noted. The System creates objective, reproducible data, without the need for any specialist expertise and compares favourably with the MSS. Greater scar numbers are required to further clinically validate this device--however, with this potential to calculate scar length, width, volume and other characteristics, it could provide a complete, objective, quantitative record of scarring throughout the wound-healing process. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Scar-free cutaneous wound healing in the leopard gecko, Eublepharis macularius.

PubMed

Peacock, Hanna M; Gilbert, Emily A B; Vickaryous, Matthew K

2015-11-01

Cutaneous wounds heal with two possible outcomes: scarification or near-perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue-level events characterising wounds that spontaneously heal scar-free, particularly in non-foetal amniotes. Here, a spatiotemporal investigation of scar-free cutaneous wound healing following full-thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell-rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar-free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar-free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar-free wound healing the newly formed blood vessels are typically perivascular cell-supported. Immunohistochemistry revealed widespread expression of both the pro-angiogenic factor vascular endothelial growth factor A and the anti-angiogenic factor thrombospondin-1 within the healing wound. It was found that scar-free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar-free wound healing. © 2015 Anatomical Society.

Scar-free cutaneous wound healing in the leopard gecko, Eublepharis macularius

PubMed Central

Peacock, Hanna M; Gilbert, Emily A B; Vickaryous, Matthew K

2015-01-01

Cutaneous wounds heal with two possible outcomes: scarification or near-perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue-level events characterising wounds that spontaneously heal scar-free, particularly in non-foetal amniotes. Here, a spatiotemporal investigation of scar-free cutaneous wound healing following full-thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell-rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar-free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar-free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar-free wound healing the newly formed blood vessels are typically perivascular cell-supported. Immunohistochemistry revealed widespread expression of both the pro-angiogenic factor vascular endothelial growth factor A and the anti-angiogenic factor thrombospondin-1 within the healing wound. It was found that scar-free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar-free wound healing. PMID:26360824

Integrins as Modulators of Transforming Growth Factor Beta Signaling in Dermal Fibroblasts During Skin Regeneration After Injury.

PubMed

Boo, Stellar; Dagnino, Lina

2013-06-01

Abnormal wound repair results from disorders in granulation tissue remodeling, and can lead to hypertrophic scarring and fibrosis. Excessive scarring can compromise tissue function and decrease tissue resistance to additional injuries. The development of potential therapies to minimize scarring is, thus, necessary to address an important clinical problem. It has been clearly established that multiple cytokines and growth factors participate in the regulation of cutaneous wound healing. More recently, it has become apparent that these factors do not necessarily activate isolated signaling pathways. Rather, in some cases, there is cross-modulation of several cellular pathways involved in this process. Two of the key pathways that modulate each other during wound healing are activated by transforming growth factor-β and by extracellular matrix proteins acting through integrins. The pathogenesis of excessive scarring upon wound healing is not fully understood, as a result of the complexity of this process. However, the fact that many pathways combine to produce fibrosis provides multiple potential therapeutic targets. Some of them have been identified, such as focal adhesion kinase and integrin-linked kinase. Currently, a major challenge is to develop pharmacological inhibitors of these proteins with therapeutic value to promote efficient wound repair. The ability to better understand how different pathways crosstalk during wound repair and to identify and pharmacologically modulate key factors that contribute to the regulation of multiple wound-healing pathways could potentially provide effective therapeutic targets to decrease or prevent excessive scar formation and/or development of fibrosis.

Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring.

PubMed

Li, Zhonghua; Wang, Haiqin; Yang, Bo; Sun, Yukai; Huo, Ran

2015-12-01

The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing. Copyright © 2015 Elsevier B.V. All rights reserved.

Detection of small subendocardial infarction using speckle tracking echocardiography in a rat model.

PubMed

Bachner-Hinenzon, Noa; Shlomo, Liron; Khamis, Hanan; Ertracht, Offir; Vered, Zvi; Malka, Assaf; Binah, Ofer; Adam, Dan

2016-10-01

It is challenging to detect small nontransmural infarcts visually or automatically. As it is important to detect myocardial infarction (MI) at early stages, we tested the hypothesis that small nontransmural MI can be detected using speckle tracking echocardiography (STE) at the acute stage. Minimal nontransmural infarcts were induced in 18 rats by causing recurrent ischemia-reperfusion of the left anterior descending (LAD) coronary artery, followed by a 30-min ligation and by reperfusion. A week later, the scar size was measured by histological analysis. Each rat underwent three echocardiography measurements: at baseline, 1 day post-MI, and 1 week post-MI. To measure the peak circumferential strain (CS), peak systolic CS, radial strain (RS), and time-to-peak (TTP) of the CS, short-axis view of the apex was analyzed by a STE program. The TTP was normalized by the duration of the heart cycle to create percent change of heart cycle. Histological analysis after 1 week showed scar size of 4±6% at the anterior wall. At 24 h post-MI, the peak CS, peak systolic CS, and RS were reduced compared to baseline at the anterior wall due to the MI, and at the adjacent segments-the anterior septum and lateral wall, due to stunning (P<.05). However, only the anterior wall, the genuine damaged segment, showed prolonged TTP vs baseline (baseline 36%, 24 h 48%, P<.05). The TTP of the CS can distinguish between regions adjacent to MI (stunned or tethered) and MI, even in small nontransmural infarcts. © 2016, Wiley Periodicals, Inc.

Morphologic and Histologic Comparison of Hypertrophic Scar in Nude Mice, T-Cell Receptor, and Recombination Activating Gene Knockout Mice.

PubMed

Momtazi, Moein; Ding, Jie; Kwan, Peter; Anderson, Colin C; Honardoust, Dariush; Goekjian, Serge; Tredget, Edward E

2015-12-01

Proliferative scars in nude mice have demonstrated morphologic and histologic similarities to human hypertrophic scar. Gene knockout technology provides the opportunity to study the effect of deleting immune cells in various disease processes. The authors' objective was to test whether grafting human skin onto T-cell receptor (TCR) αβ-/-γδ-/-, recombination activating gene (RAG)-1-/-, and RAG-2γ-/-c-/- mice results in proliferative scars consistent with human hypertrophic scar and to characterize the morphologic, histologic, and cellular changes that occur after removing immune cells. Nude TCRαβ-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice (n = 20 per strain) were grafted with human skin and euthanized at 30, 60, 120, and 180 days. Controls (n = 5 per strain) were autografted with mouse skin. Scars and normal skin were harvested at each time point. Sections were stained with hematoxylin and eosin, Masson's trichrome, and immunohistochemistry for anti-human leukocyte antigen-ABC, α-smooth muscle actin, decorin, and biglycan. TCRαβ-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice grafted with human skin developed firm, elevated scars with histologic and immunohistochemical similarities to human hypertrophic scar. Autografted controls showed no evidence of pathologic scarring. Knockout animals demonstrated a capacity for scar remodeling not observed in nude mice where reductions in α-smooth muscle actin staining pattern and scar thickness occurred over time. Human skin transplanted onto TCRαβ-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice results in proliferative scars with morphologic and histologic features of human hypertrophic scar. Remodeling of proliferative scars generated in knockout animals is analogous to changes in human hypertrophic scar. These animal models may better represent the natural history of human hypertrophic scar.

Inflammatory responses, matrix remodeling, and re-epithelialization after fractional CO2 laser treatment of scars.

PubMed

DeBruler, Danielle M; Blackstone, Britani N; Baumann, Molly E; McFarland, Kevin L; Wulff, Brian C; Wilgus, Traci A; Bailey, J Kevin; Supp, Dorothy M; Powell, Heather M

2017-09-01

Fractional CO 2 laser therapy has been used to improve scar pliability and appearance; however, a variety of treatment protocols have been utilized with varied outcomes. Understanding the relationship between laser power and extent of initial tissue ablation and time frame for remodeling could help determine an optimum power and frequency for laser treatment. The characteristics of initial injury caused by fractional CO 2 laser treatment, the rates of dermal remodeling and re-epithelialization, and the extent of inflammation as a function of laser stacking were assessed in this study in a porcine scar model. Full-thickness burn wounds were created on female Red Duroc pigs followed by immediate excision of the eschar and split-thickness autografting. Three months after injury, the resultant scars were treated with a fractional CO 2 laser with 70 mJ of energy delivered as either a single pulse or stacked for three consecutive pulses. Immediately prior to laser treatment and at 1, 24, 96, and 168 hours post-laser treatment, transepidermal water loss (TEWL), erythema, and microscopic characteristics of laser injury were measured. In addition, markers for inflammatory cytokines, extracellular matrix proteins, and re-epithelialization were quantified at all time points using qRT-PCR. Both treatments produced erythema in the scar that peaked 24 hours after treatment then decreased to basal levels by 168 hours. TEWL increased after laser treatment and returned to normal levels between 24 and 96 hours later. Stacking of the pulses did not significantly increase the depth of ablated wells or extend the presence of erythema. Interleukin 6 and monocyte chemoattractant protein-1 were found to increase significantly 1 hour after treatment but returned to baseline by 24 hours post laser. In contrast, expression of transforming growth factor β1 and transforming growth factor β3 increased slowly after treatment with a more modest increase than interleukin 6 and monocyte chemoattractant protein-1. In the current study, the properties of the ablative zones were not directly proportional to the total amount of energy applied to the porcine scars with the use of triple stacking, resulting in only minor increases to microthermal zone (MTZ) depth and width versus a single pulse. Re-epithelialization and re-establishment of epidermal barrier function were observed in laser treated scars by 48 hours post therapy. Finally, many of the inflammatory genes up-regulated by the laser ablation returned to baseline within 1 week. As a whole, these results suggest that microthermal zones created by FXCO 2 treatment re-epithelialize rapidly with the inflammatory response to the laser induced injury largely resolved within 1 week post treatment. Further study is needed to understand the relationship between laser stacking and MTZ properties in human scars in order to evaluate the clinical applicability of the stacking technique. Lasers Surg. Med. 49:675-685, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

PROSPECTIVE EVALUATION OF 18F-FDG UPTAKE IN POST-ISCHEMIC MYOCARDIUM BY SIMULTANEOUS PET/MRI AS A PROGNOSTIC MARKER OF FUNCTIONAL OUTCOME

PubMed Central

Rischpler, Christoph; Dirschinger, Ralf J.; Nekolla, Stephan G.; Kossmann, Hans; Nicolosi, Stefania; Hanus, Franziska; van Marwick, Sandra; Kunze, Karl P.; Meinicke, Alexander; Götze, Katharina; Kastrati, Adnan; Langwieser, Nicolas; Ibrahim, Tareq; Nahrendorf, Matthias; Schwaiger, Markus; Laugwitz, Karl-Ludwig

2016-01-01

Background The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by 18F-FDG PET/MRI in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI 18F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of 18F-FDG-PET/MRI in patients after AMI as a biosignal for left ventricular functional outcome. Methods and Results We prospectively enrolled 49 patients with STEMI and performed 18F-FDG-PET/MRI 5 days after PCI and follow-up cardiac MRI after 6–9 months. In a subset of patients, 99mTc-sestamibi-SPECT was performed with tracer injection prior to revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of 18F-FDG-uptake and LGE showed substantial overlap (κ=0.66), while quantitative analysis demonstrated that 18F-FDG extent exceeded LGE extent (33.2±16.2 %LV vs. 20.4±10.6 %LV, p<0.0001) and corresponded to the area-at-risk (r=0.87, p<0.0001). The peripheral blood count of CD14high/CD16+ monocytes correlated with the infarction size and 18F-FDG signal extent (r=0.53, p<0.002 and r=0.42, p<0.02, respectively). 18F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar and the SUVmean was associated with left ventricular functional outcome independent of infarct size (ΔEF: p<0.04, ΔEDV: p<0.02, ΔESV: p<0.005). Conclusions In the current study, the intensity of 18F-FDG uptake in the myocardium after AMI correlated inversely with functional outcome at 6 months. Thus, 18F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. PMID:27056601

High-Intensity Training Improves Global and Segmental Strains in Severe Congestive Heart Failure.

PubMed

Blumberg, Yair; Ertracht, Offir; Gershon, Itai; Bachner-Hinenzon, Noa; Reuveni, Tali; Atar, Shaul

2017-05-01

High-intensity training (HIT) is superior to moderate aerobic training (MAT) for improving quality of life in congestive heart failure (CHF) patients. Speckle-tracking echocardiography (STE) has recently been suggested for estimation of left ventricle global and regional function. We evaluated the utility of STE for characterizing differences in cardiac function following MAT or HIT in a CHF rat model. After baseline physiologic assessment, CHF was induced by means of coronary artery ligation in Sprague-Dawley rats. Repeated measurements confirmed the presence of CHF (ejection fraction 52 ± 10%, global circumferential strain (GCS) 10.5 ± 4, and maximal oxygen uptake (V˙O 2 max ) 71 ± 11 mL⋅min -1 ⋅kg -1 ; P < .001 vs baseline for all). Subsequently, rats were divided into training protocols: sedentary (SED), MAT, or HIT. After the training period, rats underwent the same measurements and were killed. Training intensity improved V˙O 2 max (73 ± 13 mL⋅min -1 ⋅kg -1 in MAT [P < .01 vs baseline] and 82 ± 6 mL⋅min -1 ⋅kg -1 in HIT [P < .05 vs baseline or SED] and ejection fraction (50 ± 21% in MAT [P < .001 vs baseline] and 66 ± 7% in HIT [P > .05 vs baseline]). In addition, strains of specific segments adjacent to the infarct zone regained basal values (P > .05 vs baseline), whereas global cardiac functional parameters as assessed with the use of 2-dimensional echocardiography did not improve. High-intensity exercise training improved function in myocardial segments remote from the scar, which resulted in compensatory cardiac remodeling. This effect is prominent, yet it could be detected only with the use of STE. Copyright © 2017 Elsevier Inc. All rights reserved.

Transient myocardial tissue and function changes during a marathon in less fit marathon runners.

PubMed

Gaudreault, Valerie; Tizon-Marcos, Helena; Poirier, Paul; Pibarot, Philippe; Gilbert, Philippe; Amyot, Marc; Rodés-Cabau, Josep; Després, Jean-Pierre; Bertrand, Olivier; Larose, Eric

2013-10-01

Although regular physical activity improves health, strenuous exercise might transiently increase cardiac risk. Training and fitness might provide protection. We prospectively studied 20 recreational marathon runners without known cardiovascular disease or symptoms: at peak training before, immediately after, and 3 months after a 42.2-km marathon. Changes in global/segmental myocardial function, edema, resting perfusion, and fibrosis were measured. At peak training, runners exercised 8.1 ± 2.3 hours and 62 ± 18 km per week with mean maximal oxygen consumption (VO2max) of 53.2 ± 8.3 mL/kg/min. In response to the marathon, global left ventricular and right ventricular ejection fraction decreased in half of the runners; these runners had poorer peak training distance, training time, and fitness level. Change in global left ventricular ejection fraction was associated with VO2max. Overall, 36% of segments developed edema, 53% decreased function, and 59% decreased perfusion. Significant agreement was observed between segment decreasing function, decreasing perfusion, and developing edema. Myocardial changes were reversible at 3 months. Completing a marathon leads to localized myocardial edema, diminished perfusion, and decreased function occurring more extensively in less trained and fit runners. Although reversible, these changes might contribute to the transient increase in cardiac risk reported during sustained vigorous exercise. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

An objective long-term evaluation of Integra (a dermal skin substitute) and split thickness skin grafts, in acute burns and reconstructive surgery.

PubMed

Nguyen, Dai Q A; Potokar, Tom S; Price, Patricia

2010-02-01

The field of wound healing and tissue repair has advanced rapidly in the last decade, with this there is an increasing emphasis on the importance of the functional and cosmetic outcomes following injury. Integra artificial skin is the most widely used synthetic skin substitute and is reported to have better outcomes in relation to the appearance and elasticity when compared to split thickness skin grafting (SSG). A review of the literature reveals very few trials that are based on an objective evaluation of Integra treated scars as compared to SSGs. This research aimed to provide objective data on the long-term outcome of Integra. All adult patients from the Welsh Burns Centre who had been successfully treated with Integra+/-SSG were invited to attend a clinic for a follow up provided they had been healed for greater than one year. The hypothesis that Integra scars are more pliable than skin grafts was tested objectively using the Cutometer, a suction device which measures skin elasticity. Of the 13 patients eligible, six were available for assessment. The results of this study suggest that Integra treated sites correlate well with normal skin as measured by the Cutometer. This was statistically significant for the parameters Ur/Ue (elastic function) and Ur/Uf (gross elasticity). On the other hand there was no correlation seen between the patients SSG sites and the patient's normal skin. With advances in medicine we are increasingly able to modulate wound healing and the resultant scars. In order to assess new and often costly treatments the need for objective scar measurement tools have become apparent. Integra has been advocated to improve scarring from injury. However, there have been few studies to evaluate the long-term outcome of Integra as compared to traditional methods such as SSG. In the past scar evaluation has been based on subjective scores by patients and clinicians. Now the mechanical properties of the skin can be evaluated using simple bioengineering methods such as the Cutometer Suction Device. Using this device our study has objectively demonstrated that the elastic properties of areas treated with Integra is comparable to normal skin. Copyright (c) 2009 Elsevier Ltd and ISBI. All rights reserved.

Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction

PubMed Central

Russell, Richard O.; Rackley, Charles E.; Pombo, Jaoquin; Hunt, David; Potanin, Constantine; Dodge, Harold T.

1970-01-01

Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function. Images PMID:5431663

What can we learn about treating heart failure from the heart's response to acute exercise? Focus on the coronary microcirculation.

PubMed

Heinonen, Ilkka; Sorop, Oana; de Beer, Vincent J; Duncker, Dirk J; Merkus, Daphne

2015-10-15

Coronary microvascular function and cardiac function are closely related in that proper cardiac function requires adequate oxygen delivery through the coronary microvasculature. Because of the close proximity of cardiomyocytes and coronary microvascular endothelium, cardiomyocytes not only communicate their metabolic needs to the coronary microvasculature, but endothelium-derived factors also directly modulate cardiac function. This review summarizes evidence that the myocardial oxygen balance is disturbed in the failing heart because of increased extravascular compressive forces and coronary microvascular dysfunction. The perturbations in myocardial oxygen balance are exaggerated during exercise and are due to alterations in neurohumoral influences, endothelial function, and oxidative stress. Although there is some evidence from animal studies that the myocardial oxygen balance can partly be restored by exercise training, it is largely unknown to what extent the beneficial effects of exercise training include improvements in endothelial function and/or oxidative stress in the coronary microvasculature and how these improvements are impacted by risk factors such as diabetes, obesity, and hypercholesterolemia. Copyright © 2015 the American Physiological Society.

MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction.

PubMed

Chen, Yueqiu; Zhao, Yunfeng; Chen, Weiqian; Xie, Lincen; Zhao, Zhen-Ao; Yang, Junjie; Chen, Yihuan; Lei, Wei; Shen, Zhenya

2017-11-25

Our study aim was to evaluate the therapeutic efficacy and mechanisms of miR-133-overexpressing mesenchymal stem cells (MSCs) on acute myocardial infarction. Rat MSCs were isolated and purified by whole bone marrow adherent culturing. After transfection with the agomir or antagomir of miR-133, MSCs were collected for assay of cell vitality, apoptosis, and cell cycle progression. At the same time, exosomes were isolated from the supernatant to analyze the paracrine miR-133. For in-vivo studies, constitutive activation of miR-133 in MSCs was achieved by lentivirus-mediated miR-133 overexpression. A rat myocardial infarction model was created by ligating the left anterior descending coronary artery, while control MSCs (vector-MSCs) or miR-133-overexpressed MSCs (miR-133-MSCs) were injected into the zone around the myocardial infarction. Subsequently, myocardial function was evaluated by echocardiography on days 7 and 28 post infarction. Finally the infarcted hearts were collected on days 7 and 28 for myocardial infarct size measurement and detection of snail 1 expression. Hypoxia-induced apoptosis of MSCs obviously reduced, along with enhanced expression of total poly ADP-ribose polymerase protein, after miR-133 agomir transfection, while the apoptosis rate increased in MSCs transfected with miR-133 antagomir. However, no change in cell viability and cell-cycle distribution was observed in control, miR-133-overexpressed, and miR-133-interfered MSCs. Importantly, rats transplanted with miR-133-MSCs displayed more improved cardiac function after acute myocardial infarction, compared with those that received vector-MSC injection. Further studies indicated that cardiac expression of snail 1 was significantly repressed by adjacent miR-133-overexpressing MSCs, and both the inflammatory level and the infarct size decreased in miR-133-MSC-injected rat hearts. miR-133-MSCs obviously improved cardiac function in a rat model of myocardial infarction. Transplantation of miR-133-overexpressing MSCs provides an effective strategy for cardiac repair and modulation of cardiac-related diseases.