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Sample records for chronically infarcted myocardium

  1. Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

    PubMed Central

    Neubauer, S; Horn, M; Naumann, A; Tian, R; Hu, K; Laser, M; Friedrich, J; Gaudron, P; Schnackerz, K; Ingwall, J S

    1995-01-01

    The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress. PMID:7883957

  2. Complement Component 3 is Necessary to Preserve Myocardium and Myocardial Function in Chronic Myocardial Infarction

    PubMed Central

    Wysoczynski, Marcin; Solanki, Mitesh; Borkowska, Sylwia; van Hoose, Patrick; Brittian, Kenneth R.; Prabhu, Sumanth D.; Ratajczak, Mariusz Z.; Rokosh, Gregg

    2014-01-01

    Activation of the complement cascade (CC) with myocardial infarction (MI) acutely initiates immune cell infiltration, membrane attack complex formation on injured myocytes, and exacerbates myocardial injury. Recent studies implicate the CC in mobilization of stem/progenitor cells and tissue regeneration. Its role in chronic MI is unknown. Here, we consider complement component C3, in the chronic response to MI. C3 knockout (KO) mice were studied after permanent coronary artery ligation. C3 deficiency exacerbated myocardial dysfunction 28 days after MI compared to WT with further impaired systolic function and LV dilation despite similar infarct size 24 hours post-MI. Morphometric analysis 28 days post-MI showed C3 KO mice had more scar tissue with less viable myocardium within the infarct zone which correlated with decreased c-kitpos cardiac stem/progenitor cells (CPSC), decreased proliferating Ki67pos CSPCs and decreased formation of new BrdUpos/α-sarcomeric actinpos myocytes and increased apoptosis compared to WT. Decreased CSPCs and increased apoptosis were evident 7 days post-MI in C3 KO hearts. The inflammatory response with MI was attenuated in the C3 KO and was accompanied by attenuated hematopoietic, pluripotent, and cardiac stem/progenitor cell mobilization into the peripheral blood 72 hours post-MI. These results are the first to demonstrate the CC, through C3, contributes to myocardial preservation and regeneration in response to chronic MI. Responses in the C3 KO infer that C3 activation in response to MI expands the resident CSPC population, increases new myocyte formation, increases and preserves myocardium, inflammatory response, and bone marrow stem/progenitor cell mobilization to preserve myocardial function. PMID:24806427

  3. Complement component 3 is necessary to preserve myocardium and myocardial function in chronic myocardial infarction.

    PubMed

    Wysoczynski, Marcin; Solanki, Mitesh; Borkowska, Sylwia; van Hoose, Patrick; Brittian, Kenneth R; Prabhu, Sumanth D; Ratajczak, Mariusz Z; Rokosh, Gregg

    2014-09-01

    Activation of the complement cascade (CC) with myocardial infarction (MI) acutely initiates immune cell infiltration, membrane attack complex formation on injured myocytes, and exacerbates myocardial injury. Recent studies implicate the CC in mobilization of stem/progenitor cells and tissue regeneration. Its role in chronic MI is unknown. Here, we consider complement component C3, in the chronic response to MI. C3 knockout (KO) mice were studied after permanent coronary artery ligation. C3 deficiency exacerbated myocardial dysfunction 28 days after MI compared to WT with further impaired systolic function and LV dilation despite similar infarct size 24 hours post-MI. Morphometric analysis 28 days post-MI showed C3 KO mice had more scar tissue with less viable myocardium within the infarct zone which correlated with decreased c-kit(pos) cardiac stem/progenitor cells (CPSC), decreased proliferating Ki67(pos) CSPCs and decreased formation of new BrdU(pos) /α-sarcomeric actin(pos) myocytes, and increased apoptosis compared to WT. Decreased CSPCs and increased apoptosis were evident 7 days post-MI in C3 KO hearts. The inflammatory response with MI was attenuated in the C3 KO and was accompanied by attenuated hematopoietic, pluripotent, and cardiac stem/progenitor cell mobilization into the peripheral blood 72 hours post-MI. These results are the first to demonstrate that CC, through C3, contributes to myocardial preservation and regeneration in response to chronic MI. Responses in the C3 KO infer that C3 activation in response to MI expands the resident CSPC population, increases new myocyte formation, increases and preserves myocardium, inflammatory response, and bone marrow stem/progenitor cell mobilization to preserve myocardial function. © 2014 AlphaMed Press.

  4. Angiogenesis in the Infarcted Myocardium

    PubMed Central

    Cochain, Clement; Channon, Keith M.

    2013-01-01

    Abstract Significance: Proangiogenic therapy appeared a promising strategy for the treatment of patients with acute myocardial infarction (MI), as de novo formation of microvessels, has the potential to salvage ischemic myocardium at early stages after MI, and is also essential to prevent the transition to heart failure through the control of cardiomyocyte hypertrophy and contractility. Recent Advances: Exciting preclinical studies evaluating proangiogenic therapies for MI have prompted the initiation of numerous clinical trials based on protein or gene transfer delivery of growth factors and administration of stem/progenitor cells, mainly from bone marrow origin. Nonetheless, these clinical trials showed mixed results in patients with acute MI. Critical Issues: Even though methodological caveats, such as way of delivery for angiogenic growth factors (e.g., protein vs. gene transfer) and stem/progenitor cells or isolation/culture procedure for regenerative cells might partially explain the failure of such trials, it appears that delivery of a single growth factor or cell type does not support angiogenesis sufficiently to promote cardiac repair. Future Directions: Optimization of proangiogenic therapies might include stimulation of both angiogenesis and vessel maturation and/or the use of additional sources of stem/progenitor cells, such as cardiac progenitor cells. Experimental unraveling of the mechanisms of angiogenesis, vessel maturation, and endothelial cell/cardiomyocyte cross talk in the ischemic heart, analysis of emerging pathways, as well as a better understanding of how cardiovascular risk factors impact endogenous and therapeutically stimulated angiogenesis, would undoubtedly pave the way for the development of novel and hopefully efficient angiogenesis targeting therapeutics for the treatment of acute MI. Antioxid. Redox Signal. 18, 1100–1113. PMID:22870932

  5. Phenotypically heterogeneous podoplanin-expressing cell populations are associated with the lymphatic vessel growth and fibrogenic responses in the acutely and chronically infarcted myocardium

    PubMed Central

    Cimini, Maria; Cannatá, Antonio; Pasquinelli, Gianandrea; Rota, Marcello

    2017-01-01

    Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of LYVE-1-negative cells dispersed between myocytes, predominantly in the vicinity of the infarcted region. Podoplanin-carrying populations displayed a mesenchymal progenitor marker PDGFRα, and intermittently expressed Prox-1, a master regulator of the lymphatic endothelial fate. At the stages of scar formation and maturation, concomitantly with the enlargement of lymphatic network in the injured myocardium, the podoplanin-rich LYVE-1-negative multicellular assemblies were apparent in the fibrotic area, aligned with extracellular matrix deposits, or located in immediate proximity to activated blood vessels with high VEGFR-2 content. Of note, these podoplanin-containing cells acquired the expression of PDGFRβ or a hematoendothelial epitope CD34. Although Prox-1 labeling was abundant in the area affected by MI, the podoplanin-presenting cells were not consistently Prox-1-positive. The concordance of podoplanin with VEGFR-3 similarly varied. Thus, our data reveal previously unknown phenotypic and structural heterogeneity within the podoplanin-positive cell compartment in the infarcted heart, and suggest an alternate ability of podoplanin-presenting cardiac cells to generate lymphatic endothelium and pro

  6. Cardiac Telocytes in Regeneration of Myocardium After Myocardial Infarction.

    PubMed

    Zhaofu, Liao; Dongqing, Cai

    2016-01-01

    Recent research progress has revealed that a novel type of interstitial cells termed cardiac telocytes (CTs) is found in the interstitium of the heart. We demonstrated that CTs are distributed both longitudinally and within the cross network in the myocardium and that the density of CTs in the atrium-atria and base of the myocardium is higher than that in the middle of the myocardium, while the density of CTs in the epicardium is higher than that in the endocardium. In addition, we documented, for the first time, that the network of CTs in the infarct zone of the myocardium is destroyed during myocardial infarction (MI). This fact shows that, in addition to the death of cardiac myocytes, the previously unrecognized death of CTs is an important mechanism that contributes to the structural damage and poor healing and regeneration observed in the infarcted myocardium. Furthermore, we demonstrated, for the first time, that transplantation of CTs in cases of MI decreases the infarct size and improves myocardial function. The mechanisms behind the beneficial effects of CT transplantation are increased angiogenesis at the infarct site and the border zone, decreased fibrosis in the infarct and non-infarct zones, improved pathological reconstruction of the left ventricle, and increased regeneration of CTs in the infarct zone. Our findings reveal that CTs can be specifically identified by the following characteristics: very small cell bodies, extreme prolongation with some dilation, predisposition to cell death under ischemia, and expression of molecular markers such as c-Kit, CD34, vimentin, and PDGFR-β. CTs act as a structural and functional niche microenvironment in the myocardium and play an essential role in maintaining the integrity of the myocardium and in the regeneration of damaged myocardium.

  7. Engineering and visualization of bacteria for targeting infarcted myocardium.

    PubMed

    Le, Uyenchi N; Kim, Hyung-Seok; Kwon, Jin-Sook; Kim, Mi Yeon; Nguyen, Vu H; Jiang, Sheng Nan; Lee, Byeong-Il; Hong, Yeongjin; Shin, Myung Geun; Rhee, Joon Haeng; Bom, Hee-Seung; Ahn, Youngkeun; Gambhir, Sanjiv S; Choy, Hyon E; Min, Jung-Joon

    2011-05-01

    Optimization of the specific affinity of cardiac delivery vector could significantly improve the efficiency of gene/protein delivery, yet no cardiac vectors to date have sufficient target specificity for myocardial infarction (MI). In this study, we explored bacterial tropism for infarcted myocardium based on our previous observations that certain bacteria are capable of targeting the hypoxic regions in solid tumors. Out of several Escherichia coli or Salmonella typhimurium strains, the S. typhimurium defective in the synthesis of ppGpp (ΔppGpp S. typhimurium) revealed accumulation and selective proliferation in the infarcted myocardium without spillover to noncardiac tissue. The Salmonellae that were engineered to express a variant of Renilla luciferase gene (RLuc8), under the control of the E. coli arabinose operon promoter (P(BAD)), selectively targeted and delivered RLuc8 in the infarcted myocardium only upon injection of L-arabinose. An examination of the infarct size before and after infection, and estimations of C-reactive protein (CRP) and procalcitonin indicated that intravenous injection of ΔppGpp S. typhimurium did not induce serious local or systemic immune reactions. This current proof-of-principle study demonstrates for the first time the capacity of Salmonellae to target infarcted myocardium and to serve as a vehicle for the selective delivery of therapeutic agents in MI.

  8. Engineering and Visualization of Bacteria for Targeting Infarcted Myocardium

    PubMed Central

    Le, Uyenchi N; Kim, Hyung-Seok; Kwon, Jin-Sook; Kim, Mi Yeon; Nguyen, Vu H; Jiang, Sheng Nan; Lee, Byeong-Il; Hong, Yeongjin; Shin, Myung Geun; Rhee, Joon Haeng; Bom, Hee-Seung; Ahn, Youngkeun; Gambhir, Sanjiv S; Choy, Hyon E; Min, Jung-Joon

    2011-01-01

    Optimization of the specific affinity of cardiac delivery vector could significantly improve the efficiency of gene/protein delivery, yet no cardiac vectors to date have sufficient target specificity for myocardial infarction (MI). In this study, we explored bacterial tropism for infarcted myocardium based on our previous observations that certain bacteria are capable of targeting the hypoxic regions in solid tumors. Out of several Escherichia coli or Salmonella typhimurium strains, the S. typhimurium defective in the synthesis of ppGpp (ΔppGpp S. typhimurium) revealed accumulation and selective proliferation in the infarcted myocardium without spillover to noncardiac tissue. The Salmonellae that were engineered to express a variant of Renilla luciferase gene (RLuc8), under the control of the E. coli arabinose operon promoter (PBAD), selectively targeted and delivered RLuc8 in the infarcted myocardium only upon injection of -arabinose. An examination of the infarct size before and after infection, and estimations of C-reactive protein (CRP) and procalcitonin indicated that intravenous injection of ΔppGpp S. typhimurium did not induce serious local or systemic immune reactions. This current proof-of-principle study demonstrates for the first time the capacity of Salmonellae to target infarcted myocardium and to serve as a vehicle for the selective delivery of therapeutic agents in MI. PMID:21364539

  9. Magnetic resonance imaging dynamic contrast enhancement (DCE) characteristics of healed myocardial infarction differ from viable myocardium.

    PubMed

    Goldfarb, James W; Zhao, Wenguo

    2014-12-01

    To determine whether healed myocardial infarction alters dynamic contrast-enhancement (DCE) curve shapes as well as late gadolinium-enhancement (LGE). Twenty patients with chronic myocardial infarction underwent MR imaging at 1.5 T with blood and myocardial T1 measurements before and after contrast administration for forty minutes. Viable and infarcted myocardial partition coefficients were calculated using multipoint slope methods for ten different DCE sampling intervals and windows. Partition coefficients and coefficients of determination were compared with paired statistical tests to assess the linearity of DCE curve shapes over the 40 min time period. Calculated partition coefficients did not vary significantly between methods (p=0.325) for viable myocardium but did differ for infarcted myocardium (p<0.001), indicating a difference in infarcted DCE. There was a significant difference between viable and infarcted myocardial partition coefficients estimates for all methods with the exception of methods that included measurements during the first 10 min after contrast agent administration. Myocardial partition coefficients calculated from a slope calculation vary in healed myocardial infarction based on the selection of samples due to non-linear DCE curve shapes. Partition coefficient calculations are insensitive to data sampling effects in viable myocardium due to linear DCE curve shapes. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Melatonin-induced glycosaminoglycans augmentation in myocardium remote to infarction.

    PubMed

    Drobnik, J; Tosik, D; Piera, L; Szczepanowska, A; Olczak, S; Zielinska, A; Liberski, P P; Ciosek, J

    2013-12-01

    Elevated levels of collagen as well as transient increases of glycosaminoglycans (GAG) have been shown in the myocardium remote to the infarction. The aim of the study is to observe the effect of melatonin on the accumulation of collagen and GAG in the left ventricle wall, remote to the infarction. A second aim is to determine whether the effect of the pineal indole is mediated by the membrane melatonin receptors of heart fibroblasts. Rats with myocardial infarction induced by ligation of the left coronary artery were treated with melatonin at a dose of 60 μg/100 g b.w. or vehicle (2% ethanol in 0.9% NaCl). The results were compared with an untreated control. In the second part of the study, the fibroblasts from the non-infarcted part of myocardium were isolated and cultured. Melatonin at a range of concentrations from 10(-8) M to 10(-6) M was applied to the fibroblast cultures. In the final part of the study, the influence of luzindole (10(-6) M), the melatonin membrane receptor inhibitor, on melatonin-induced GAG augmentation was investigated. Both collagen and GAG content were measured in the experiment. Melatonin elevated GAG content in the myocardium remote to the infarcted heart. Collagen level was not changed by pineal indoleamine. Fibroblasts isolated from the myocardium varied in shape from fusiform to spindle-shaped. Moreover, the pineal hormone (10(-7)M and 10(-6)M) increased GAG accumulation in the fibroblast culture. Luzindole inhibited melatonin-induced elevation of GAG content at 10(-6)M. Melatonin increased GAG content in the myocardium remote to infarction. This effect was dependent on the direct influence of the pineal indole on the heart fibroblasts. The melatonin-induced GAG elevation is blocked by luzindole, the melatonin membrane receptors inhibitor, indicating a direct effect of this indole.

  11. The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction.

    PubMed

    Wang, Yiming; Liu, Xingde; Zhang, Dongfeng; Chen, Jianhui; Liu, Shuzheng; Berk, Michael

    2013-02-08

    There is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear. Our previous study demonstrated an increase in pro-apoptotic pathways in the myocardium and hippocampus in MDD, which was reversed by venlafaxine. This study aimed to attempt to confirm the effects of apoptosis vulnerability markers on the myocardium in a model of depression after myocardial infarction. Rats were divided into four groups: sham (N = 8), depression (N = 8, chronic mild unpredictable stress and separation were used in the depression group), MI (N = 13) and post-MI depression (N = 7). The rats in all four groups underwent the same open field and sucrose preference behavioral tests. Evan Blue staining was used to determine the area at risk of myocardial infarction in the left ventricle, and 2,3,5-triphenyl tetrazolium chloride (1.5% TTC) dye was used to detect the size of the myocardial infarction. The expression of bax and bcl-2 protein in the myocardium was investigated by immunohistochemistry, and the mRNA expression of bax, bcl-2 and caspase-3 in the myocardium was investigated by real time RT-PCR. Apoptosis was estimated in the myocardium by measuring the Bax:Bcl-2 ratio. In the depression and post-MI depression rats, there were significantly decreased movements and total sucrose consumption, modeling behavioral deficits and an anhedonic-like state. In terms of myocardial infarction size, no difference was seen between the MI and post-MI depression groups. There was an up-regulated Bax:Bcl-2 ratio in the depression, MI and post-MI depression groups. Furthermore, in the latter group, there was a greater up-regulated Bax:Bcl-2 ratio. However, caspase-3 did not differ among the four groups. These results of this animal model suggest that active pro-apoptotic pathways may be involved in the nexus between myocardial infarction and depression. This mechanism may be

  12. The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction

    PubMed Central

    2013-01-01

    Background There is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear. Our previous study demonstrated an increase in pro-apoptotic pathways in the myocardium and hippocampus in MDD, which was reversed by venlafaxine. This study aimed to attempt to confirm the effects of apoptosis vulnerability markers on the myocardium in a model of depression after myocardial infarction. Methods Rats were divided into four groups: sham (N = 8), depression (N = 8, chronic mild unpredictable stress and separation were used in the depression group), MI (N = 13) and post-MI depression (N = 7). The rats in all four groups underwent the same open field and sucrose preference behavioral tests. Evan Blue staining was used to determine the area at risk of myocardial infarction in the left ventricle, and 2,3,5-triphenyl tetrazolium chloride (1.5% TTC) dye was used to detect the size of the myocardial infarction. The expression of bax and bcl-2 protein in the myocardium was investigated by immunohistochemistry, and the mRNA expression of bax, bcl-2 and caspase-3 in the myocardium was investigated by real time RT-PCR. Apoptosis was estimated in the myocardium by measuring the Bax:Bcl-2 ratio. Results In the depression and post-MI depression rats, there were significantly decreased movements and total sucrose consumption, modeling behavioral deficits and an anhedonic-like state. In terms of myocardial infarction size, no difference was seen between the MI and post-MI depression groups. There was an up-regulated Bax:Bcl-2 ratio in the depression, MI and post-MI depression groups. Furthermore, in the latter group, there was a greater up-regulated Bax:Bcl-2 ratio. However, caspase-3 did not differ among the four groups. Conclusions These results of this animal model suggest that active pro-apoptotic pathways may be involved in the nexus between myocardial

  13. 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

  14. Differential MR delayed enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media.

    PubMed

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

    2015-01-01

    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. 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. 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. 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

  15. Large myocardial infarction with myocardium calcium deposits associated with reperfusion injury.

    PubMed

    Rios, Elisabete; Mancio, Jennifer; Rodrigues-Pereira, Pedro; Magalhães, Domingos; Bartosch, Carla

    2014-01-01

    The clinical and autopsy findings of a 66-year-old man with myocardial infarction complicated by reperfusion injury are described, highlighting the presence of large myocardium calcium deposits. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Effects of myocardial infarction on the distribution and transport of nutrients and oxygen in porcine myocardium.

    PubMed

    Davis, Bryce H; Morimoto, Yoshihisa; Sample, Chris; Olbrich, Kevin; Leddy, Holly A; Guilak, Farshid; Taylor, Doris A

    2012-10-01

    One of the primary limitations of cell therapy for myocardial infarction is the low survival of transplanted cells, with a loss of up to 80% of cells within 3 days of delivery. The aims of this study were to investigate the distribution of nutrients and oxygen in infarcted myocardium and to quantify how macromolecular transport properties might affect cell survival. Transmural myocardial infarction was created by controlled cryoablation in pigs. At 30 days post-infarction, oxygen and metabolite levels were measured in the peripheral skeletal muscle, normal myocardium, the infarct border zone, and the infarct interior. The diffusion coefficients of fluorescein or FITC-labeled dextran (0.3-70 kD) were measured in these tissues using fluorescence recovery after photobleaching. The vascular density was measured via endogenous alkaline phosphatase staining. To examine the influence of these infarct conditions on cells therapeutically used in vivo, skeletal myoblast survival and differentiation were studied in vitro under the oxygen and glucose concentrations measured in the infarct tissue. Glucose and oxygen concentrations, along with vascular density were significantly reduced in infarct when compared to the uninjured myocardium and infarct border zone, although the degree of decrease differed. The diffusivity of molecules smaller than 40 kD was significantly higher in infarct center and border zone as compared to uninjured heart. Skeletal myoblast differentiation and survival were decreased stepwise from control to hypoxia, starvation, and ischemia conditions. Although oxygen, glucose, and vascular density were significantly reduced in infarcted myocardium, the rate of macromolecular diffusion was significantly increased, suggesting that diffusive transport may not be inhibited in infarct tissue, and thus the supply of nutrients to transplanted cells may be possible. in vitro studies mimicking infarct conditions suggest that increasing nutrients available to

  17. Pathological Mechanism for Delayed Hyperenhancement of Chronic Scarred Myocardium in Contrast Agent Enhanced Magnetic Resonance Imaging

    PubMed Central

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

    2014-01-01

    Objectives To evaluate possible mechanism for delayed hyperenhancement of scarred myocardium by investigating the relationship of contrast agent (CA) first pass and delayed enhancement patterns with histopathological changes. Materials and Methods Eighteen pigs underwent 4 weeks ligation of 1 or 2 diagonal coronary arteries to induce chronic infarction. The hearts were then removed and perfused in a Langendorff apparatus. The hearts firstly experienced phosphorus 31 MR spectroscopy. The hearts in group I (n = 9) and II (n = 9) then received the bolus injection of Gadolinium diethylenetriamine pentaacetic acid (0.05 mmol/kg) and gadolinium-based macromolecular agent (P792, 15 µmol/kg), respectively. First pass T2* MRI was acquired using a gradient echo sequence. Delayed enhanced T1 MRI was acquired with an inversion recovery sequence. Masson's trichrome and anti- von Willebrand Factor (vWF) staining were performed for infarct characterization. Results Wash-in of both kinds of CA caused the sharp and dramatic T2* signal decrease of scarred myocardium similar to that of normal myocardium. Myocardial blood flow and microvessel density were significantly recovered in 4-week-old scar tissue. Steady state distribution volume (ΔR1 relaxation rate) of Gd-DTPA was markedly higher in scarred myocardium than in normal myocardium, whereas ΔR1 relaxation rate of P792 did not differ significantly between scarred and normal myocardium. The ratio of extracellular volume to the total water volume was significantly greater in scarred myocardium than in normal myocardium. Scarred myocardium contained massive residual capillaries and dilated vessels. Histological stains indicated the extensively discrete matrix deposition and lack of cellular structure in scarred myocardium. Conclusions Collateral circulation formation and residual vessel effectively delivered CA into scarred myocardium. However, residual vessel without abnormal hyperpermeability allowed Gd-DTPA rather than

  18. [The application of hemoreologic indicators in prognosis of complications of acute myocardium infarction].

    PubMed

    Pakhrova, O A; Kudriashova, M V; Grineva, M R; Mishina, I E

    2015-02-01

    The sampling of 60 patients with acute myocardium infarction underwent a complex study of hemoreologic indicators with purpose to establish predictors of development of early complications of diseases to substantiate additions to algorithm of examination and to differentiate treatment regimens. It is established that under acute myocardium infarction the blood viscosity increases on low velocity of shifting and plasma. Also, the process of aggregation of erythrocytes increases and number of normocytes decreases without significant alterations of blood viscosity on high velocity of shift and capacity of erythrocytes to be distorted. At the same time, the mentioned above alterations in patients with acute myocardium infarction does not result in decreasing of effectiveness oftransportation of oxygen to tissues. Against the background of development the hemoreologic disorders have more apparent character and result in progressive decreasing of tissue perfusion. The most significant prognostic indicator concerning complications of acute myocardium infarction is a time parameter of increment of aggregation of erythrocytes surpassing 2.80 in 89% of patients with complications. The expedience of inclusion of detection of reologic blood indicators fir their subsequent correction in the complex of examination ofpatients with acute myocardium infarction.

  19. Classification of normal and infarcted myocardium based on statistical analysis of high-frequency intracardiac ultrasound rf signal

    NASA Astrophysics Data System (ADS)

    Hao, Xiaohui; Bruce, Charles; Pislaru, Cristina; Greenleaf, James F.

    2002-04-01

    Myocardial structural changes caused by infarction / reperfusion may result in increased scatterer density and variation of scatterer arrangement in ultrasound imaging. Homodyned K (HD_K) distribution is employed in this paper to model the backscattered signal from both normal and reperfused infarcted myocardium and is used to characterize them. Statistical testing showed that among the Rayleigh, K, Nakagami and Homodyned K distributions, the Homodyned K distribution is the best model to describe ultrasound signal backscattered from both normal and infarcted reperfused myocardium. Using HD_K distribution, in vivo demodulated RF data (8.5MHz) from anterior myocardial wall, as imaged from both left and right ventricle at baseline and after infarction/reperfusion, were analyzed. Significant increase of scatterer density in reperfused infarcted myocardium has been found compared to the normal myocardium. We concluded that HD_K distribution has potential to distinguish reperfused infarcted myocardium from normal using high frequency ultrasound imaging, irrespective of LV or RV data acquisition.

  20. Collateral circulation formation determines the characteristic profiles of contrast-enhanced MRI in the infarcted myocardium of pigs

    PubMed Central

    Wang, Jian; Xiang, Bo; Lin, Hung-yu; Liu, Hong-yu; Freed, Darren; Arora, Rakesh C; Tian, Gang-hong

    2015-01-01

    Aim: To investigate the relationship between the collateral circulation and contrast-enhanced MR signal change for myocardial infarction (MI) in pigs. Methods: Pigs underwent permanent ligation of two diagonal branches of the left anterior descending artery. First-pass perfusion (FPP) MRI (for detecting myocardial perfusion abnormalities) and delayed enhancement (DE) MRI (for estimating myocardial infarction) using Gd-DTPA were performed at 2 h, 7 d and 4 weeks after the coronary occlusion. Myocardial blood flow (MBF) was evaluated using nonradioactive red-colored microspheres. Histological examination was performed to characterize the infarcts. Results: Acute MI performed at 2 h afterwards was characterized by hypoenhancement in both FPP- and DE-MRI, with small and almost unchanged FPP-signal intensity (SI) and DE-SI due to negligible MBF. Subacute MI detected 7 d afterwards showed small but significantly increaseing FPP-SI, and was visible as a sluggish hyperenhancement in DE-MRI with considerably higher DE-SI compared to the normal myocardium; the MBF approached the half-normal value. Chronic MI detected at 4 weeks afterwards showed increasing FPP-SI comparable to the normal myocardium, and a rapid hyperenhancement in DE-MRI with even higher DE-SI; the MBF was close to the normal value. The MBF was correlated with FPP-SI (r=+0.94, P<0.01) and with the peak DE-SI (r=+0.92, P<0.01) at the three MI stages. Remodeled vessels were observed at intra-infarction and peri-infarction zones during the subacute and chronic periods. Conclusion: Progressive collateral recovery determines the characteristic profiles of contrast-enhanced MRI in acute, subacute and chronic myocardial infarction in pigs. The FPP- and DE-MRI signal profiles not only depend on the loss of tissue viability and enlarged interstitial space, but also on establishing a collateral circulation. PMID:25832427

  1. Collateral circulation formation determines the characteristic profiles of contrast-enhanced MRI in the infarcted myocardium of pigs.

    PubMed

    Wang, Jian; Xiang, Bo; Lin, Hung-yu; Liu, Hong-yu; Freed, Darren; Arora, Rakesh C; Tian, Gang-hong

    2015-04-01

    To investigate the relationship between the collateral circulation and contrast-enhanced MR signal change for myocardial infarction (MI) in pigs. Pigs underwent permanent ligation of two diagonal branches of the left anterior descending artery. First-pass perfusion (FPP) MRI (for detecting myocardial perfusion abnormalities) and delayed enhancement (DE) MRI (for estimating myocardial infarction) using Gd-DTPA were performed at 2 h, 7 d and 4 weeks after the coronary occlusion. Myocardial blood flow (MBF) was evaluated using nonradioactive red-colored microspheres. Histological examination was performed to characterize the infarcts. Acute MI performed at 2 h afterwards was characterized by hypoenhancement in both FPP- and DE-MRI, with small and almost unchanged FPP-signal intensity (SI) and DE-SI due to negligible MBF. Subacute MI detected 7 d afterwards showed small but significantly increaseing FPP-SI, and was visible as a sluggish hyperenhancement in DE-MRI with considerably higher DE-SI compared to the normal myocardium; the MBF approached the half-normal value. Chronic MI detected at 4 weeks afterwards showed increasing FPP-SI comparable to the normal myocardium, and a rapid hyperenhancement in DE-MRI with even higher DE-SI; the MBF was close to the normal value. The MBF was correlated with FPP-SI (r=+0.94, P<0.01) and with the peak DE-SI (r=+0.92, P<0.01) at the three MI stages. Remodeled vessels were observed at intra-infarction and peri-infarction zones during the subacute and chronic periods. Progressive collateral recovery determines the characteristic profiles of contrast-enhanced MRI in acute, subacute and chronic myocardial infarction in pigs. The FPP- and DE-MRI signal profiles not only depend on the loss of tissue viability and enlarged interstitial space, but also on establishing a collateral circulation.

  2. Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction.

    PubMed

    Aoki, Hirofumi; Matsunari, Ichiro; Nomura, Yusuke; Fujita, Wataru; Komatsu, Ryoko; Miyazaki, Yoshiharu; Nekolla, Stephan G; Kajinami, Kouji

    2013-07-01

    The purpose of this study was to investigate the relationship between sympathetic innervation, contractile function, and the oxidative metabolism of the non-infarcted myocardium in patients with prior myocardial infarction. In 19 patients (14 men, 5 women, 65 ± 9 years) after prior myocardial infarction, sympathetic innervation was assessed by (11)C-hydroxyephedrine (HED) positron emission tomography (PET). Oxidative metabolism was quantified using (11)C-acetate PET. Left ventricular systolic function was measured by echocardiography with speckle tracking technique. The (11)C-HED retention was positively correlated with left ventricular ejection fraction (LVEF) (r = 0.566, P < 0.05), and negatively with peak longitudinal strain in systole in the non-infarcted myocardium (r = -0.561, P < 0.05). Kmono, as an index of oxidative metabolism, was significantly correlated with rate pressure product (r = 0.649, P < 0.01), but not with (11)C-HED retention (r = 0.188, P = 0.442). Furthermore, there was no significant correlation between Kmono and LVEF (r = 0.106, P = 0.666) or peak longitudinal strain in systole (r = -0.256, P = 0.291) in the non-infarcted myocardium. When the patients were divided into two groups based on the median value of left ventricular end-systolic volume index (LVESVI) (41 mL), there were no significant differences in age, sex, and rate pressure product between the groups. However, the large LVESVI group (>41 mL) was associated with reduced (11)C-HED retention and peak longitudinal strain in systole, whereas Kmono was similar between the groups. This study indicates that remodeled LV after myocardial infarction is associated with impaired sympathetic innervation and function even in the non-infarcted myocardial tissue. Furthermore, oxidative metabolism in the non-infarcted myocardium seems to be operated by normal regulatory mechanisms rather than pre-synaptic sympathetic neuronal function.

  3. VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium

    PubMed Central

    Zhao, Tieqiang; Zhao, Wenyuan; Meng, Weixin; Liu, Chang; Chen, Yuanjian; Gerling, Ivan C; Weber, Karl T; Bhattacharya, Syamal K; Kumar, Rahul; Sun, Yao

    2015-01-01

    Background: Numerous studies have shown that in addition to angio/lymphangiogenesis, the VEGF family is involved in other cellular actions. We have recently reported that enhanced VEGF-C and VEGFR-3 in the infarcted rat myocardium, suggesting the paracrine/autocrine function of VEGF-C on cardiac remodeling. The current study was designed to test the hypothesis that VEGF-C regulates cardiomyocyte growth and survival in the infarcted myocardium. Methods and results: Gene profiling and VEGFR-3 expression of cardiomyocytes were assessed by laser capture microdissection/microarray and immunohistochemistry in the normal and infarcted myocardium. The effect of VEGF-C on myocyte hypertrophy and apoptosis during normoxia and hypoxia was detected by RT-PCR and western blotting in cultured rat neonatal cardiomyocytes. VEGFR-3 was minimally expressed in cardiomyocytes of the normal and noninfarcted myocardium, while markedly elevated in the surviving cardiomyocytes of the infarcted myocardium and border zone. Genes altered in the surviving cardiomyocytes were associated with the networks regulating cellular growth and survival. VEGF-C significantly increased the expression of atrial natriuretic factor (ANP), brain natriuretic factor (BNP), and β-myosin heavy chain (MHC), markers of hypertrophy, in neonatal cardiomyocytes. Hypoxia caused neonatal cardiomyocyte atrophy, which was prevented by VEGF-C treatment. Hypoxia significantly enhanced apoptotic mediators, including cleaved caspase 3, 8, and 9, and Bax in neonatal cardiomyocytes, which were abolished by VEGF-C treatment. Conclusion: Our findings indicate that VEGF-C/VEGFR-3 pathway exerts a beneficial role in the infarcted myocardium by promoting compensatory cardiomyocyte hypertrophy and survival. PMID:26064438

  4. Ultrasmall superparamagnetic particles of iron oxide (USPIO) MR imaging of infarcted myocardium in pigs.

    PubMed

    Kroft, L J; Doornbos, J; van der Geest, R J; van der Laarse, A; van der Meulen, H; de Roos, A

    1998-09-01

    The purpose of this study is to assess the potential value of ultrasmall superparamagnetic iron oxide (USPIO) for the detection of acute myocardial infarction by magnetic resonance (MR) imaging. Spin-echo magnetic resonance imaging of the heart was performed before, immediately after, and approximately 35 and 90 min after 30 micromol Fe/kg of USPIO administration in seven pigs with surgically induced myocardial infarction. Gradient-echo sequences were used to identify contraction abnormalities at the site of infarction. Myocardial signal intensities were measured using region-of-interest analysis in normal and infarcted myocardium. In addition, liver and lung signal intensities were measured. Pathologic correlation was performed after sacrificing the animals. The infarct area was located with wall-motion analysis. The site of infarction was confirmed at pathologic examination. The signal-intensity ratio between infarcted and normal myocardium was not significantly changed after USPIO administration at equilibrium stages (immediately after injection p = 0.64, at 35 min p = 0.32, at 90 min p = 0.73). The signal intensity of the liver decreased significantly after contrast administration (p < 0.05). For the lung, the change in signal intensity after USPIO administration was not significant. This pig model is well suited to study wall motion abnormalities after induction of acute myocardial infarction. USPIO-enhanced magnetic resonance imaging does not improve the visualization of acute myocardial infarction at equilibrium stage.

  5. Acute myocardial infarction: estimation of at-risk and salvaged myocardium at myocardial perfusion SPECT 1 month after infarction.

    PubMed

    Romero-Farina, Guillermo; Aguadé-Bruix, Santiago; Candell-Riera, Jaume; Pizzi, M Nazarena; Pineda, Victor; Figueras, Jaume; Cuberas, Gemma; de León, Gustavo; Castell-Conesa, Joan; García-Dorado, David

    2013-11-01

    To estimate at-risk and salvaged myocardium by using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging after acute myocardial infarction (AMI). The study was approved by the hospital's Ethical Committee on Clinical Trials (trial register number, PR(HG)36/2000), and all patients gave informed consent. Forty patients (mean age, 61.78 years; eight women) with a first AMI underwent two gated SPECT examinations--one before percutaneous coronary intervention (PCI) and one 4-5 weeks after PCI. Myocardium at risk was estimated by assessing the perfusion defect at the first gated SPECT examination, and salvaged myocardium was estimated by assessing the risk area minus necrosis at the second examination. Myocardium at risk was estimated by determining the discordance between the areas of left ventricular (LV) wall motion and perfusion at the second examination. Concordance between tests was analyzed by means of linear regression analysis, the Pearson correlation, the intraclass correlation coefficient, and Bland-Altman analysis. An improvement in perfusion, wall motion, wall thickening, and LV ejection fraction (P < .001) was observed at 1 month. At 1 month, the area with abnormal wall motion was greater than the area of altered perfusion (35.47 vs 23.1 cm(2); P = .007). The extent of myocardium at risk estimated from this discordance correlated well with myocardium at risk measured at the first gated SPECT examination and with salvaged myocardium between both studies (Pearson correlation: 0.78 and 0.6, respectively). Concordance for correct classification of patients with salvaged myocardium of 50% or greater was 83% (κ = 0.65). Myocardial perfusion gated SPECT performed 1 month after early PCI in a first AMI provides potentially useful information on at-risk and salvaged myocardium. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122324/-/DC1. RSNA, 2013

  6. Sympathetic denervation of peri-infarct myocardium requires the p75 neurotrophin receptor.

    PubMed

    Lorentz, Christina U; Parrish, Diana C; Alston, Eric N; Pellegrino, Michael J; Woodward, William R; Hempstead, Barbara L; Habecker, Beth A

    2013-11-01

    Development of cardiac sympathetic heterogeneity after myocardial infarction contributes to ventricular arrhythmias and sudden cardiac death. Regions of sympathetic hyperinnervation and denervation appear in the viable myocardium beyond the infarcted area. While elevated nerve growth factor (NGF) is implicated in sympathetic hyperinnervation, the mechanisms underlying denervation are unknown. Recent studies show that selective activation of the p75 neurotrophin receptor (p75(NTR)) in sympathetic neurons causes axon degeneration. We used mice that lack p75(NTR) to test the hypothesis that activation of p75(NTR) causes peri-infarct sympathetic denervation after cardiac ischemia-reperfusion. Wild type hearts exhibited sympathetic denervation adjacent to the infarct 24h and 3 days after ischemia-reperfusion, but no peri-infarct sympathetic denervation occurred in p75(NTR)-/- mice. Sympathetic hyperinnervation was found in the distal peri-infarct myocardium in both genotypes 3 days after MI, and hyperinnervation was increased in the p75(NTR)-/- mice. By 7 days after ischemia-reperfusion, cardiac sympathetic innervation density returned back to sham-operated levels in both genotypes, indicating that axonal pruning did not require p75(NTR). Prior studies revealed that proNGF is elevated in the damaged left ventricle after ischemia-reperfusion, as is mRNA encoding brain-derived neurotrophic factor (BDNF). ProNGF and BDNF preferentially bind p75(NTR) rather than TrkA on sympathetic neurons. Immunohistochemistry using Bdnf-HA mice confirmed the presence of BDNF or proBDNF in the infarct after ischemia-reperfusion. Thus, at least two p75(NTR) ligands are elevated in the left ventricle after ischemia-reperfusion where they may stimulate p75(NTR)-dependent denervation of peri-infarct myocardium. In contrast, NGF-induced sympathetic hyperinnervation in the distal peri-infarct ventricle is attenuated by p75(NTR).

  7. Mesenchymal stem cell-loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium.

    PubMed

    Wang, Qiang-Li; Wang, Hai-Jie; Li, Zhi-Hua; Wang, Yong-Li; Wu, Xue-Ping; Tan, Yu-Zhen

    2017-02-28

    Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tβ4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tβ4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit(+) cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit(+) cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.

  8. Polarization birefringence measurements for characterizing the myocardium, including healthy, infarcted, and stem-cell-regenerated tissues

    NASA Astrophysics Data System (ADS)

    Wood, Michael F. G.; Ghosh, Nirmalya; Wallenburg, Marika A.; Li, Shu-Hong; Weisel, Richard D.; Wilson, Brian C.; Li, Ren-Ke; Vitkin, I. Alex

    2010-07-01

    Myocardial infarction leads to structural remodeling of the myocardium, in particular to the loss of cardiomyocytes due to necrosis and an increase in collagen with scar formation. Stem cell regenerative treatments have been shown to alter this remodeling process, resulting in improved cardiac function. As healthy myocardial tissue is highly fibrous and anisotropic, it exhibits optical linear birefringence due to the different refractive indices parallel and perpendicular to the fibers. Accordingly, changes in myocardial structure associated with infarction and treatment-induced remodeling will alter the anisotropy exhibited by the tissue. Polarization-based linear birefringence is measured on the myocardium of adult rat hearts after myocardial infarction and compared with hearts that had received mesenchymal stem cell treatment. Both point measurement and imaging data show a decrease in birefringence in the region of infarction, with a partial rebound back toward the healthy values following regenerative treatment with stem cells. These results demonstrate the ability of optical polarimetry to characterize the micro-organizational state of the myocardium via its measured anisotropy, and the potential of this approach for monitoring regenerative treatments of myocardial infarction.

  9. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function

    PubMed Central

    Linke, Axel; Müller, Patrick; Nurzynska, Daria; Casarsa, Claudia; Torella, Daniele; Nascimbene, Angelo; Castaldo, Clotilde; Cascapera, Stefano; Böhm, Michael; Quaini, Federico; Urbanek, Konrad; Leri, Annarosa; Hintze, Thomas H.; Kajstura, Jan; Anversa, Piero

    2005-01-01

    The purpose of this study was to determine whether the heart in large mammals contains cardiac progenitor cells that regulate organ homeostasis and regenerate dead myocardium after infarction. We report that the dog heart possesses a cardiac stem cell pool characterized by undifferentiated cells that are self-renewing, clonogenic, and multipotent. These clonogenic cells and early committed progeny possess a hepatocyte growth factor (HGF)–c-Met and an insulin-like growth factor 1 (IGF-1)-IGF-1 receptor system that can be activated to induce their migration, proliferation, and survival. Therefore, myocardial infarction was induced in chronically instrumented dogs implanted with sonomicrometric crystals in the region of the left ventricular wall supplied by the occluded left anterior descending coronary artery. After infarction, HGF and IGF-1 were injected intramyocardially to stimulate resident cardiac progenitor cells. This intervention led to the formation of myocytes and coronary vessels within the infarct. Newly generated myocytes expressed nuclear and cytoplasmic proteins specific of cardiomyocytes: MEF2C was detected in the nucleus, whereas α-sarcomeric actin, cardiac myosin heavy chain, troponin I, and α-actinin were identified in the cytoplasm. Connexin 43 and N-cadherin were also present. Myocardial reconstitution resulted in a marked recovery of contractile performance of the infarcted heart. In conclusion, the activation of resident primitive cells in the damaged dog heart can promote a significant restoration of dead tissue, which is paralleled by a progressive improvement in cardiac function. These results suggest that strategies capable of activating the growth reserve of the myocardium may be important in cardiac repair after ischemic injury. PMID:15951423

  10. Coronary flow reserve in the remote myocardium predicts left ventricular remodeling following acute myocardial infarction.

    PubMed

    Cheng, Rongchao; Wei, Guoqian; Yu, Longhao; Su, Zhendong; Wei, Li; Bai, Xiuping; Tian, Jiawei; Li, Xueqi

    2014-07-01

    Coronary flow reserve (CFR) in the non-infarcted myocardium is often impaired following acute myocardial infarction (AMI). However, the clinical significance of CFR in the non-infarcted myocardium is not fully understood. The objective of the present study was to assess whether a relationship exists between CFR and left ventricular remodeling following AMI. We enrolled 18 consecutive patients undergoing coronary intervention. Heart function was analyzed using real-time myocardial contrast echocardiography at one week and six months after coronary angioplasty. Ten subjects were enrolled as the control group and were examined using the same method at the same time to assess CFR. Cardiac troponin I (cTnI) levels were routinely analyzed to estimate peak concentration. CFR was 1.55±0.11 in the infarcted zone and 2.05±0.31 in the remote zone (p<0.01) at one week following AMI. According to CFR values in the remote zone, all patients were divided into two groups: Group I (CFR <2.05) and Group II (CFR >2.05). The levels of cTnI were higher in Group I compared to Group II on admission (36.40 vs. 21.38, p<0.05). Furthermore, left ventricular end diastolic volume was higher in Group I compared to Group II at six months following coronary angioplasty. Microvascular dysfunction is commonly observed in the remote myocardium. The CFR value accurately predicts adverse ventricular remodeling following AMI.

  11. Mummification of the infarcted myocardium by high dose corticosteroids.

    PubMed

    Kloner, R A; Fishbein, M C; Lew, H; Maroko, P R; Braunwald, E

    1978-01-01

    There is evidence that glucocorticoids reduce infarct size but their use in myocardial infarction remains controversial because of their potential adverse effects on healing of the infarct. To investigate the healing process, rats received either four parenteral doses of 50 mg/kg of methylprednisolone (MP) or saline 5 min, 3,6 and 24 hr after coronary occlusion and their hearts were examined by light and electron microscopy 48 hr and seven days after occlusion. At 48 hr, in five untreated rats, only 12 +/- 7% of injured myocytes showed the persistence of striations and a relatively intact sarcolemma despite loss of nuclei and hence appeared "mummified" whereas in six MP-treated rats 72 +/- 8% of myocytes exhibited this appearance (P less than 0.001). In treated rats there were fewer phagocytes than in controls. At seven days, in seven MP-rats, mummified cells were still more prominent than in five untreated rats and there were fewer phagocytes and less collagen. In conclusion, high dose of MP delays the inflammatory process and retards the disintegration of necrotic myocytes, resulting in impaired healing.

  12. Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction.

    PubMed

    Nakamori, Shiro; Alakbarli, Javid; Bellm, Steven; Motiwala, Shweta R; Addae, Gifty; Manning, Warren J; Nezafat, Reza

    2017-10-01

    To compare remote myocardium native T1 in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T1 in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI. A total of 41 chronic MI (18 anterior MI) patients and 15 age-matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T1 map was performed using a slice interleaved T1 mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass. The remote myocardium native T1 time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P < 0.05). Remote myocardium native T1 moderately correlated with LV volume, mass index, and ejection fraction (r = 0.38, 0.50, -0.49, respectively, all P < 0.05). LGE infarct size had a moderate correlation with reduced LV ejection fraction (r = -0.33, P < 0.05), but there was no significant association between native T1 and infarct size. Native T1 time in the remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (β = -0.34, P = 0.03). In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T1 in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post-MI LV dysfunction. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1073-1081. © 2017 International Society for Magnetic Resonance in Medicine.

  13. Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host

    PubMed Central

    Léobon, Bertrand; Garcin, Isabelle; Menasché, Philippe; Vilquin, Jean-Thomas; Audinat, Etienne; Charpak, Serge

    2003-01-01

    Survival and differentiation of myogenic cells grafted into infarcted myocardium have raised the hope that cell transplantation becomes a new therapy for cardiovascular diseases. The approach was further supported by transplantation of skeletal myoblasts, which was shown to improve cardiac performance in several animal species. Despite the success of myoblast transplantation and its recent trial in human, the mechanism responsible for the functional improvement remains unclear. Here, we used intracellular recordings coupled to video and fluorescence microscopy to establish whether myoblasts, genetically labeled with enhanced GFP and transplanted into rat infarcted myocardium, retain excitable and contractile properties, and participate actively to cardiac function. Our results indicate that grafted myoblasts differentiate into peculiar hyperexcitable myotubes with a contractile activity fully independent of neighboring cardiomyocytes. We conclude that mechanisms other than electromechanical coupling between grafted and host cells are involved in the improvement of cardiac function. PMID:12805561

  14. Pathology of acute ischemic myocardium. Special references to (I) evaluation of morphological methods for detection of early myocardial infarcts, and (II) lipid metabolism in infarcted myocardium.

    PubMed

    Sakurai, I

    1977-09-01

    Morphological changes of early myocardial infarction within 24 hours after the onset of the acute attack were described together with a review of the literatures. For the practical purpose in detecting very early infarcts, enzymatic histochemistry is the most reliable method. Other methods previously reported such as wavy pattern of the muscle fibers and fuchsinophilia are still controvertial. Lipid metabolism in the infarcted myocardium of dogs was studied both morphologically and biochemically. Up to 3 hours, after the coronary ligation, the tissue lipids accumulated in the necrotic areas with a rise of triglyceride, but later than 6 hours the lipids decreased and were lost from the necrotic tissue, while the surrounding living cells were accumulated with neutral lipids. Serum free fatty acids were elevated in the coronary sinus blood in 6 hours after the ligation. Linolic acids were contained in high proportion in both coronary venous blood after 6 hours, and normal myocardial phospholipid. These results may lead to another possible factor in addition to catecholamine activity to elevate serum FFA in acute myocardial infarction that fatty acids may be released partly from tissue phospholipid and once ever accumulated triglyceride.

  15. Rapid initial reduction of hyperenhanced myocardium after reperfused first myocardial infarction suggests recovery of the peri-infarction zone: one-year follow-up by MRI.

    PubMed

    Engblom, Henrik; Hedström, Erik; Heiberg, Einar; Wagner, Galen S; Pahlm, Olle; Arheden, Håkan

    2009-01-01

    The time course and magnitude of infarct involution, functional recovery, and normalization of infarct-related electrocardiographic (ECG) changes after acute myocardial infarction (MI) are not completely known in humans. We sought to explore these processes early after MI and during infarct-healing using cardiac MRI. Twenty-two patients with reperfused first-time MI were examined by MRI and ECG at 1, 7, 42, 182, and 365 days after infarction. Global left ventricular function and regional wall thickening were assessed by cine MRI, and injured myocardium was depicted by delayed contrast-enhanced MRI. Infarct size by ECG was estimated by QRS scoring. The reduction of hyperenhanced myocardium occurred predominantly during the first week after infarction (64% of the 1-year reduction). Furthermore, during the first week the amount of nonhyperenhanced myocardium increased significantly (P<0.001), although the left ventricular mass remained unchanged. Left ventricular ejection fraction increased gradually, whereas the greater the regional transmural extent of hyperenhancement at day 1, the later the recovery of regional wall thickening. Regional wall thickening decreased progressively with increasing initial transmural extent of hyperenhancement (P(trend)<0.0001). The time course and magnitude of decrease in QRS score corresponded with the reduction of hyperenhanced myocardium. The early reduction of hyperenhanced myocardium may reflect recovery of hyperenhanced, reversibly injured myocardium, which must be considered when predicting functional recovery from delayed contrast-enhanced MRI findings early after infarction. Also, the time course and magnitude for reduction of hyperenhanced myocardium were associated with normalization of infarct-related ECG changes.

  16. Coronary Flow Reserve in the Remote Myocardium Predicts Left Ventricular Remodeling Following Acute Myocardial Infarction

    PubMed Central

    Cheng, Rongchao; Wei, Guoqian; Yu, Longhao; Su, Zhendong; Wei, Li; Bai, Xiuping; Tian, Jiawei

    2014-01-01

    Purpose Coronary flow reserve (CFR) in the non-infarcted myocardium is often impaired following acute myocardial infarction (AMI). However, the clinical significance of CFR in the non-infarcted myocardium is not fully understood. The objective of the present study was to assess whether a relationship exists between CFR and left ventricular remodeling following AMI. Materials and Methods We enrolled 18 consecutive patients undergoing coronary intervention. Heart function was analyzed using real-time myocardial contrast echocardiography at one week and six months after coronary angioplasty. Ten subjects were enrolled as the control group and were examined using the same method at the same time to assess CFR. Cardiac troponin I (cTnI) levels were routinely analyzed to estimate peak concentration. Results CFR was 1.55±0.11 in the infarcted zone and 2.05±0.31 in the remote zone (p<0.01) at one week following AMI. According to CFR values in the remote zone, all patients were divided into two groups: Group I (CFR <2.05) and Group II (CFR >2.05). The levels of cTnI were higher in Group I compared to Group II on admission (36.40 vs. 21.38, p<0.05). Furthermore, left ventricular end diastolic volume was higher in Group I compared to Group II at six months following coronary angioplasty. Conclusion Microvascular dysfunction is commonly observed in the remote myocardium. The CFR value accurately predicts adverse ventricular remodeling following AMI. PMID:24954317

  17. Signaling factors in stem cell-mediated repair of infarcted myocardium.

    PubMed

    Vandervelde, S; van Luyn, M J A; Tio, R A; Harmsen, M C

    2005-08-01

    Myocardial infarction leads to scar formation and subsequent reduced cardiac performance. The ultimate therapy after myocardial infarction would pursue stem cell-based regeneration. The aim of stem cell-mediated cardiac repair embodies restoration of cardiac function by regeneration of healthy myocardial tissue, which is accomplished by neo-angiogenesis and cardiogenesis. A major reservoir of adult autologous stem cells distal from the heart is the bone marrow. Adequate regulation of signaling between the bone marrow, the peripheral circulation and the infarcted myocardium is important in orchestrating the process of mobilization, homing, incorporation, survival, proliferation and differentiation of stem cells, that leads to myocardial regeneration. In this review, we discuss key signaling factors, including cytokines, chemokines and growth factors, which are involved in orchestrating the stem cell driven repair process. We focus on signaling factors known for their mobilizing and chemotactic abilities (SDF-1, G-CSF, SCF, IL-8, VEGF), signaling factors that are expressed after myocardial infarction involved in the patho-physiological healing process (TNF-alpha, IL-8, IL-10, HIF-1alpha, VEGF, G-CSF) and signaling factors that are involved in cardiogenesis and neo-angiogenesis (VEGF, EPO, TGF-beta, HGF, HIF-1alpha, IL-8). The future therapeutic application and capacity of secreted factors to modulate tissue repair after myocardial infarction relies on the intrinsic potency of factors and on the optimal localization and timing of a combination of signaling factors to stimulate stem cells in their niche to regenerate the infarcted heart.

  18. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

    PubMed Central

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng

    2015-01-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation. PMID:25432986

  19. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation.

    PubMed

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng; Guo, Changfa; Wang, Chunsheng

    2015-05-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation.

  20. Myocardial infarction causes inflammation and leukocyte recruitment at remote sites in the myocardium and in the renal glomerulus.

    PubMed

    Ruparelia, Neil; Digby, Janet E; Jefferson, Andrew; Medway, Debra J; Neubauer, Stefan; Lygate, Craig A; Choudhury, Robin P

    2013-05-01

    Acute myocardial infarction (AMI) results in the recruitment of leukocytes to injured myocardium. Additionally, myocardium remote to the infarct zone also becomes inflamed and is associated with adverse left ventricular remodelling. Renal ischaemic syndromes have been associated with remote organ inflammation and impaired function. Here, we tested the hypothesis that AMI results in remote organ (renal) inflammation. Mice were subjected to either AMI, sham procedure or no procedure and the inflammatory response in peripheral blood, injured and remote myocardium, and kidneys was studied at 24 h. AMI resulted in increased circulating neutrophils (P < 0.001) and monocytes (P < 0.001). mRNA for inflammatory mediators significantly increased in infarcted myocardium and in remote myocardium. VCAM-1 mRNA was increased in both infarcted and remote myocardium. VCAM-1 protein was also increased in the kidneys of AMI mice (P < 0.05) and immunofluorescence revealed localisation of VCAM-1 to glomeruli, associated with leukocyte infiltration and increased local inflammatory mRNA expression. We conclude that in addition to local inflammation, AMI results in remote organ inflammation evidenced by (1) increased expression of mRNA for inflammatory cytokines, (2) marked upregulation of VCAM-1 in renal glomeruli, and (3) the recruitment and infiltration of leukocytes in the kidney.

  1. Extra-cellular expansion in the normal, non-infarcted myocardium is associated with worsening of regional myocardial function after acute myocardial infarction.

    PubMed

    Garg, Pankaj; Broadbent, David A; Swoboda, Peter P; Foley, James R J; Fent, Graham J; Musa, Tarique A; Ripley, David P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Haaf, Philip; Kidambi, Ananth; Crandon, Saul; Chew, Pei G; van der Geest, R J; Greenwood, John P; Plein, Sven

    2017-09-25

    Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI). Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h-72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre-/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT). From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, -1.78 ± 9%, -2.9 ± 10.9%, respectively; P < 0.001). Normal segments which demonstrated deterioration in wall thickening at follow-up showed significantly increased Δ ECV compared with normal segments with preserved wall thickening at follow up (1.82 ± 6.05% versus -0.10 ± 6.88%, P < 0.05). Following reperfused STEMI, normal myocardium demonstrates subtle expansion of the extracellular volume at 3-month follow up. Segmental ECV expansion of normal myocardium is associated with worsening of contractile function.

  2. Usefulness of residual ischemic myocardium within prior infarct zone for identifying patients at high risk late after acute myocardial infarction

    SciTech Connect

    Brown, K.A.; Weiss, R.M.; Clements, J.P.; Wackers, F.J.

    1987-07-01

    This study examines the prognostic implications of ischemia within the territory of a prior acute myocardial infarction (AMI) vs ischemia at a distance, which develops late after AMI. Sixty-one consecutive patients who underwent both exercise thallium-201 (TI-201) imaging and cardiac catheterization for evaluation of chest pain that developed after discharge from the hospital for AMI form the study group. Mean interval between infarction to the TI-201 study was 10 +/- 17 months. Initial and 2-hour delay TI-201 images were analyzed quantitatively to determine the presence and location (within vs outside the prior infarct zone) of TI-201 redistribution, a marker of ischemic viable myocardium. TI-201 imaging results were separated into 3 groups based on presence and location of TI-201 redistribution: no significant TI-201 redistribution was found in 16 patients; in 29, TI-201 redistribution was confined to the infarct zone; and in 16, TI-201 redistribution was outside the infarct zone. Stepwise multivariate logistic regression analysis was used to examine the comparative ability of TI-201 results and other patient variables to predict cardiac events. For total cardiac events (cardiac death, recurrent nonfatal AMI, unstable angina and coronary revascularization), both the presence of any TI-201 redistribution and multivessel angiographic coronary artery disease were significant predictors. However, when coronary revascularization was excluded as an endpoint, TI-201 redistribution limited to the prior infarct zone was the only significant predictor of cardiac events. All 8 cardiac events occurred in patients with T1-201 redistribution limited to the infart zone.

  3. Transplantation of genetically engineered cardiac fibroblasts producing recombinant human erythropoietin to repair the infarcted myocardium

    PubMed Central

    Ruvinov, Emil; Sharabani-Yosef, Orna; Nagler, Arnon; Einbinder, Tom; Feinberg, Micha S; Holbova, Radka; Douvdevani, Amos; Leor, Jonathan

    2008-01-01

    Background Erythropoietin possesses cellular protection properties. The aim of the present study was to test the hypothesis that in situ expression of recombinant human erythropoietin (rhEPO) would improve tissue repair in rat after myocardial infarction (MI). Methods and results RhEPO-producing cardiac fibroblasts were generated ex vivo by transduction with retroviral vector. The anti-apoptotic effect of rhEPO-producing fibroblasts was evaluated by co-culture with rat neonatal cardiomyocytes exposed to H2O2-induced oxidative stress. Annexin V/PI assay and DAPI staining showed that compared with control, rhEPO forced expression markedly attenuated apoptosis and improved survival of cultured cardiomyocytes. To test the effect of rhEPO on the infarcted myocardium, Sprague-Dawley rats were subjected to permanent coronary artery occlusion, and rhEPO-producing fibroblasts, non-transduced fibroblasts, or saline, were injected into the scar tissue seven days after infarction. One month later, immunostaining identified rhEPO expression in the implanted engineered cells but not in controls. Compared with non-transduced fibroblasts or saline injection, implanted rhEPO-producing fibroblasts promoted vascularization in the scar, and prevented cell apoptosis. By two-dimensional echocardiography and postmortem morphometry, transplanted EPO-engineered fibroblasts did not prevent left ventricular (LV) dysfunction and adverse LV remodeling 5 and 9 weeks after MI. Conclusion In situ expression of rhEPO enhances vascularization and reduces cell apoptosis in the infarcted myocardium. However, local EPO therapy is insufficient for functional improvement after MI in rat. PMID:19014419

  4. Acute myocardial infarction in early pregnancy: definition of myocardium at risk with noncontrast T2-weighted cardiac magnetic resonance.

    PubMed

    Zaidi, Ali N; Raman, Subha V; Cook, Stephen C

    2008-03-01

    We report a case of a 34-year-old woman who had a left anterior wall myocardial infarction develop in the first trimester of pregnancy. Despite urgent and successful revascularization, she demonstrated persistent segmental wall motion abnormalities by transthoracic echocardiography. To manage this patient safely through pregnancy with a better definition of myocardium at risk, a cardiac magnetic resonance examination was performed. This identified a large territory of acutely edematous myocardium in addition to providing accurate volumetric measurements of left ventricular size and function. Because of her gravid state, gadolinium was not administered nor was it required to delineate the region of myocardium at risk.

  5. [The rat ventricular myocardium in chronic hypercapnia. Electron microscopic study].

    PubMed

    Reichart, E; Moravec, J; Moravec, M; Marotte, F; Hatt, P Y

    1975-11-01

    An electron microscope study of the left ventricular myocardium from rat acclimatized to chronic hypercapnia was done in order to complete the preceding work concerning general effects of respiratory acidosis. After 15 and 30 days of the acclimatation to 8% CO2 no lesions of the myocardium could be found. The results of the morphometric analysis indicated, however, discrete modifications of heart ultrastructure similar to those found before in hypoxic and failing hearts: namely a decrease of mitochondrial mean diameter and a non significant decrease of mitochondrial fractional volume. The latter was accompanied by a significant decrease of myofibrillar mass. The presence of cellular oedema seems to be suggested by an increase of fractional volume of the cytosol. The mechanism of these changes is not easy to explain. Further work will be necessary to make a choice between two possibilities: (1) depressed contractility related to some direct effect of high pCO2 and (2) tissue hypoxia secondary to local effects of the former.

  6. Molecular MRI of Acute Necrosis with a Novel DNA-Binding Gadolinium Chelate: Kinetics of Cell Death and Clearance in Infarcted Myocardium

    PubMed Central

    Huang, Shuning; Chen, Howard H.; Yuan, Hushan; Dai, Guangping; Schuhle, Daniel T.; Mekkaoui, Choukri; Ngoy, Soeun; Liao, Ronglih; Caravan, Peter; Josephson, Lee; Sosnovik, David E.

    2012-01-01

    Background Current techniques to image cell death in the myocardium are largely non-specific. Here we report the use of a novel DNA-binding gadolinium chelate (Gd-TO) to specifically detect the exposed DNA in acutely necrotic (ruptured) cells in vivo. Methods and Results In vivo MRI was performed in 20 mice with myocardial infarction (MI). The mice were injected with Gd-TO or Gd-DTPA at varying time points post-MI. MRI was performed 2 hours after probe injection, to avoid nonspecific signal from the late gadolinium enhancement effect. Cell rupture (Gd-TO uptake) was present within 2 hours of infarction, but peaked 9–18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R1) in the infarct was seen in mice injected with Gd-TO within 48 hours of MI, but not in those injected more than 72 hours post MI (R1 = 1.24 ± 0.08 and 0.92 ± 0.03 s−1, respectively, p < 0.001). Gd-DTPA, unlike Gd-TO, washed completely out of acute infarcts within 2 hours of injection (p < 0.001). The binding of Gd-TO to exposed DNA in acute infarcts was confirmed with fluorescence microscopy. Conclusions Gd-TO specifically binds to acutely necrotic cells and can be used to image the mechanism and chronicity of cell death in injured myocardium. Cell rupture in acute MI begins early but peaks many hours after the onset of injury. The ruptured cells are efficiently cleared by the immune system and are no longer present in the myocardium 72 hours after injury. PMID:21836081

  7. Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction

    SciTech Connect

    Fujita, M.; Ohno, A.; Wada, O.; Miwa, K.; Nozawa, T.; Yamanishi, K.; Sasayama, S. )

    1991-08-01

    The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 {plus minus} 0.5 (SD), which was significantly higher than the 0.7 {plus minus} 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area.

  8. MicroRNA miR-1 is up-regulated in remote myocardium in patients with myocardial infarction.

    PubMed

    Bostjancic, E; Zidar, N; Stajner, D; Glavac, D

    2010-01-01

    MicroRNAs are small regulatory RNA molecules that mediate regulation of gene expression, thus affecting a variety of physiological, developmental and pathological conditions. They are believed to be new promising therapeutic targets. In recent studies two muscle-specific microRNAs were discovered to contribute to heart diseases and development: miR-1 and miR-133, but there is little data on their expression patterns in human myocardial infarction. We performed simultaneous expression analysis of miR-1, miR-133a, miR-133b in samples of infarcted tissue and remote myocardium from twenty- four patients with acute myocardial infarction. MicroRNA expression was analysed using quantitative real-time PCR and compared to the expression patterns in myocardium of eight healthy adults who died in accidents. We found ~3.8-fold miR-1 up-regulation in remote myocardium when compared to infarcted tissue or healthy adult hearts. As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients. In addition, miR-133a/b down-regulation in infarcted tissue and remote myocardium was observed, indicating miR-133a/b involvement in the heart response to myocardial infarction. We conclude that miR-1 and miR-133 seem to be important regulators of heart adaptation after ischaemic stress.

  9. [Influences of percutaneous coronary intervention on myocardial activity in myocardial infarction patients with different viable myocardium].

    PubMed

    Li, Li-qi; Liu, Xiao-hong; Zhang, Jin; Lai, Chun-lin; He, Ye-xin

    2013-10-01

    To evaluate the effect of percutaneous coronary intervention (PCI) on left ventricular function in patients with different types of myocardial infarction and to explore the correlation factors for the left ventricular function. A total of 43 patients diagnosed as acute myocardial infarction were enrolled in this study. The perfusion and delayed enhancement magnetic resonance imaging (DE-MRI) was applied to observe the following parameters before the PCI and at month 6 after the procedure: infarct mass, left ventricular ejection fraction (LVEF) and abnormal wall motion score. The subjects were divided into the following three groups by the transmural extent of myocardial infarction manifested in the DE-MRI: the transmural enhancement group, the nontransmural group and the mixed group. Laboratory test was done to detect the level of endothelin (ET), matrix metal enzyme 9 (MMP-9) and high sensitive C reactive protein (hsCRP) before PCI and at month 6 after the procedure. The t test was used to compare the differences among the groups and the multiple regression analysis was taken to explore the correlation factors for the left ventricular function. Compared with the parameters before PCI, the infarct mass after PCI significantly decreased in the nontransmural group and the mixed group [(4.0 ± 2.9) g/cm(3) vs (9.8 ± 5.6) g/cm(3) and (6.0 ± 3.5) g/cm(3) vs (11.8 ± 6.2)g/cm(3), all P < 0.05], while LVEF was significantly improved after PCI in both groups [(52.6 ± 15.4)% vs (41.9 ± 16.3)%,(45.6 ± 15.4)% vs (38.9 ± 16.3)%, all P < 0.05]. The infarct mass was an independent correlation factor for LVEF before PCI (RR = 0.318, P < 0.05) and LVEF after PCI (RR = 0.293, P < 0.05) . LVEF before PCI was independently correlated with the level of hsCRP (RR = 0.318, P < 0.05). The effect of PCI on the improvement of left ventricular function differs in patients with different extent of myocardial infarction, which is correlated with the amount of survival myocardium and the

  10. In situ electrostimulation drives a regenerative shift in the zone of infarcted myocardium.

    PubMed

    Spadaccio, Cristiano; Rainer, Alberto; De Marco, Federico; Lusini, Mario; Gallo, Paolo; Sedati, Pietro; Muda, Andrea Onetti; De Porcellinis, Stefano; Gregorj, Chiara; Avvisati, Giuseppe; Trombetta, Marcella; Chello, Massimo; Covino, Elvio; Bull, David A; Patel, Amit N; Genovese, Jorge A

    2013-01-01

    Electrostimulation represents a well-known trophic factor for different tissues. In vitro electrostimulation of non-stem and stem cells induces myogenic predifferentiation and may be a powerful tool to generate cells with the capacity to respond to local areas of injury. We evaluated the effects of in vivo electrostimulation on infarcted myocardium using a miniaturized multiparameter implantable stimulator in rats. Parameters of electrostimulation were organized to avoid a direct driving or pacing of native heart rhythm. Electrical stimuli were delivered for 14 days across the scar site. In situ electrostimulation used as a cell-free, cytokine-free stimulation system, improved myocardial function, and increased angiogenesis through endothelial progenitor cell migration and production of vascular endothelial growth factor (VEGF). In situ electrostimulation represents a novel means to stimulate repair of the heart and other organs, as well as to precondition tissues for treatment with cell-based therapies.

  11. Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction.

    PubMed

    Yang, Yun; Shi, Chunying; Hou, Xianglin; Zhao, Yannan; Chen, Bing; Tan, Bo; Deng, Zongwu; Li, Qingguo; Liu, Jianzhou; Xiao, Zhifeng; Miao, Qi; Dai, Jianwu

    2015-09-10

    Vascular endothelial growth factor (VEGF) promotes angiogenesis and improves cardiac function after myocardial infarction (MI). However, the non-targeted delivery of VEGF decreases its therapeutic efficacy due to an insufficient local concentration in the ischemic myocardium. In this study, we used a specific peptide to modify VEGF and determined that this modified VEGF (IMT-VEGF) localized to the ischemic myocardium through intravenous injection by interacting with cardiac troponin I (cTnI). When IMT-VEGF was used to mediate cardiac repair in a rat model of ischemia-reperfusion (I-R) injury, we observed a decreased scar size, enhanced angiogenesis and improved cardiac function. Moreover, an alternative treatment using the repeated administration of a low-dose IMT-VEGF also promoted angiogenesis and functional recovery. The therapeutic effects of IMT-VEGF were further confirmed in a pig model of MI as the result of the conserved properties of its interacting protein, cTnI. These results suggest a promising therapeutic strategy for MI based on the targeted delivery of IMT-VEGF. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction.

    PubMed

    Kalofoutis, Christos; Mourouzis, Iordanis; Galanopoulos, Georgios; Dimopoulos, Antonios; Perimenis, Philippos; Spanou, Danai; Cokkinos, Dennis V; Singh, Jaipaul; Pantos, Constantinos

    2010-12-01

    It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium. Here, we further explored whether this effect can be preserved in the presence of co-morbidities such as diabetes which accelerates cardiac remodeling and increases mortality after myocardial infarction. Acute myocardial infarction (AMI) was induced by left coronary ligation in rats with type I diabetes (DM) induced by streptozotocin administration (STZ; 35 mg/kg; i.p.) while sham-operated animals served as controls (SHAM). AMI resulted in distinct changes in cardiac function and geometry; EF% was significantly decreased in DM-AMI [37.9 ± 2.0 vs. 74.5 ± 2.1 in DM-SHAM]. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, wall tension index [WTI, the ratio of (Left Ventricular Internal Diameter at diastole)/2*(Posterior Wall thickness)], an index of wall stress, was found to be significantly increased in DM-AMI; 2.27 ± 0.08 versus 1.70 ± 0.05. 2D-Strain echocardiographic analysis showed reduced systolic radial strain in all segments, indicating increased loss of cardiac myocytes in the infarct related area and less compensatory hypertrophy in the viable segments. This response was accompanied by a marked decrease in the expression of TRα1 and TRβ1 receptors in the diabetic myocardium without changes in circulating T3 and T4. Accordingly, the expression of TH target genes related to cardiac contractility was altered; β-MHC and PKCα were significantly increased. TH (L-T4 and L-T3) administration prevented these changes and resulted in increased EF%, normal wall stress and increased systolic radial strain in all myocardial segments. Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.

  13. The role of transforming growth factor (TGF)-β in the infarcted myocardium

    PubMed Central

    2017-01-01

    The adult mammalian heart has negligible regenerative capacity. Following myocardial infarction, sudden necrosis of cardiomyocytes triggers an intense inflammatory reaction that clears the wound from dead cells and matrix debris, while activating a reparative program. A growing body of evidence suggests that members of the transforming growth factor (TGF)-β family critically regulate the inflammatory and reparative response following infarction. Although all three TGF-β isoforms (TGF-β1, -β2 and -β3) are markedly upregulated in the infarcted myocardium, information on isoform-specific actions is limited. Experimental studies have suggested that TGF-β exerts a wide range of actions on cardiomyocytes, fibroblasts, immune cells, and vascular cells. The findings are often conflicting, reflecting the context-dependence of TGF-β-mediated effects; conclusions are often based exclusively on in vitro studies and on associative evidence. TGF-β has been reported to modulate cardiomyocyte survival responses, promote monocyte recruitment, inhibit macrophage pro-inflammatory gene expression, suppress adhesion molecule synthesis by endothelial cells, promote myofibroblast conversion and extracellular matrix synthesis, and mediate both angiogenic and angiostatic effects. This review manuscript discusses our understanding of the cell biological effects of TGF-β in myocardial infarction. We discuss the relative significance of downstream TGF-β-mediated Smad-dependent and -independent pathways, and the risks and challenges of therapeutic TGF-β targeting. Considering the high significance of TGF-β-mediated actions in vivo, study of cell-specific effects and dissection of downstream signaling pathways are needed in order to design safe and effective therapeutic approaches. PMID:28446968

  14. The iron-regulatory peptide hepcidin is upregulated in the ischemic and in the remote myocardium after myocardial infarction.

    PubMed

    Simonis, Gregor; Mueller, Katrin; Schwarz, Peggy; Wiedemann, Stephan; Adler, Guido; Strasser, Ruth H; Kulaksiz, Hasan

    2010-09-01

    Recent evidence suggests that iron metabolism contributes to the ischemic damage after myocardial infarction. Hepcidin, a recently discovered peptide hormone, regulates iron uptake and metabolism, protecting the body from iron overload. In this study we analyzed the regulation of hepcidin in the heart and blood of rats after myocardial infarction. To induce a myocardial infarction in the rats, left anterior descending coronary artery ligation was performed. After 1-24h, biopsies from the ischemic and the non-ischemic myocardium were taken. In these biopsies, the mRNA levels and the protein expression of hepcidin were analyzed by quantitative RT-PCR and immunoblot analysis, respectively. In parallel, the serum levels of prohepcidin were measured by ELISA. Six hours after myocardial infarction, the hepcidin mRNA expression was temporally upregulated in the ischemic and in the non-ischemic myocardium. The upregulation was specific for hepcidin, since other iron-related genes (hemojuvelin, IREG-1) remained unchanged. Furthermore, the alteration of the hepcidin protein expression in the ischemic area was connected to the level of hepcidin in the serum of the infarcted rats, where hepcidin also raised up. Angiotensin receptor blockade with candesartan did not influence the mRNA regulation of hepcidin. Together, these data show a particular upregulation of the iron-regulatory peptide hepcidin in the ischemic and the non-ischemic myocardium after myocardial infarction. It is speculated that upregulation of hepcidin may reduce iron toxicity and thus infarct size expansion in an infarcted heart. Copyright 2010 Elsevier Inc. All rights reserved.

  15. The role of insulin-like and basic fibroblast growth factors on ischemic and infarcted myocardium: a mini review.

    PubMed

    Scheinowitz, M; Abramov, D; Eldar, M

    1997-03-01

    Current therapeutic techniques in acute myocardial infarction (AMI) are inadequate since restoration of blood flow through the obstructed coronary artery does not always preserve the ischemic myocardium. Therefore, deterioration of cardiac function and detrimental left ventricular remodeling may follow. Alternative therapeutic modalities are now being actively sought. Insulin-like growth factor (IGF) and fibroblast growth factor (FGF) are two polypeptides found in wide distribution and high concentrations in the normal myocardium. They play a key role in vascular growth (FGF) and affect the differentiation of cardiac myocytes (IGF). IGF has been found to promote physiological forms of cardiac hypertrophy, and FGF induces neovascularization. During myocardial ischemia and infarction there is a marked elevation in the concentration of these growth promoting factors in the myocardium concomitant with increased coronary collateral blood flow, neovascularization and peri-infarct hypertrophy. In animal models of myocardial infarction, exogenous administration of FGF and IGF induced neovascularization and cardiac hypertrophy thus, preserving cardiac function. We assume that these growth factors may become an additional tool in the future treatment of patients with AMI.

  16. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium.

    PubMed

    Zhang, Dongsheng; Fan, Guo-Chang; Zhou, Xiaoyang; Zhao, Tiemin; Pasha, Zeeshan; Xu, Meifeng; Zhu, Yi; Ashraf, Muhammad; Wang, Yigang

    2008-02-01

    Bone marrow mesenchymal stem cells (MSCs) participate in myocardial repair following myocardial infarction. However, their in vivo reparative capability is limited due to lack of their survival in the infarcted myocardium. To overcome this limitation, we genetically engineered male rat MSCs overexpressing CXCR4 in order to maximize the effect of stromal cell-derived factor-1alpha (SDF-1alpha) for cell migration and regeneration. MSCs were isolated from adult male rats and cultured. Adenoviral transduction was carried out to over-express either CXCR4/green fluorescent protein (Ad-CXCR4/GFP) or Ad-null/GFP alone (control). Flow cytometry was used to identify and isolate GFP/CXCR4 over-expressing MSCs for transplantation. Female rats were assigned to one of four groups (n=8 each) to receive GFP-transduced male MSCs (2 x 10(6)) via tail vein injection 3 days after ligation of the left anterior descending (LAD) coronary artery: GFP-transduced MSCs (Ad-null/GFP-MSCs, group 1) or MSCs over-expressing CXCR4/GFP (Ad-CXCR4/GFP-MSCs, group 2), or Ad-CXCR4/GFP-MSCs plus SDF-1alpha (50 ng/microl) (Ad-CXCR4/GFP-MSCs/SDF-1alpha, group 3), or Ad-miRNA targeting CXCR4 plus SDF-1alpha (Ad-miRNA/GFP-MSCs+SDF-1alpha treatment, group 4). Cardiodynamic data were obtained 4 weeks after induction of regional myocardial infarction (MI) using echocardiography after which hearts were harvested for immunohistochemical studies. The migration of GFP and Y-chromosome positive cells increased significantly in the peri- and infarct areas of groups 2 and 3 compared to control group (p<0.05), or miRNA-CXCR4 group (p<0.01). The number of CXCR4 positive cells in groups 2, 3 was intimately associated with angiogenesis and myogenesis. MSCs engraftment was blocked by pretreatment with miRNA (group 4). Cardiac function was significantly improved in rats receiving MSCs over-expressing CXCR4 alone or with SDF-1alpha. The up-regulation of matrix metalloproteinases (MMPs) by CXCR4 overexpressing MSCs perhaps

  17. 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

  18. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

    PubMed

    Gerbin, Kaytlyn A; Yang, Xiulan; Murry, Charles E; Coulombe, Kareen L K

    2015-01-01

    Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC)-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle) delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz). Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they identify lack of

  19. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts

    PubMed Central

    Gerbin, Kaytlyn A.; Yang, Xiulan; Murry, Charles E.; Coulombe, Kareen L. K.

    2015-01-01

    Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC)-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle) delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300–390 beats per minute (5–6.5 Hz). Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart’s pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they identify lack of

  20. Non-excitatory electrical stimulation attenuates myocardial infarction via homeostasis of calcitonin gene-related peptide in myocardium.

    PubMed

    Guo, Zhi-Jia; Guo, Zheng

    2015-03-01

    Electrical stimulation has been shown protection of brain, retina, optic nerves and pancreatic β-cells but the effect on cardio-protection is still unknown. Calcitonin gene-related peptide (CGRP) participates in the pathology of injury and protection of myocardium but whether or not electrical stimulation modulates endogenous CGRP is not clear. Male Sprague-Dawley rats were divided into 4 groups: (1) control group, without any treatment. (2) I/R group, animals were subjected to 30 min of myocardial ischemia followed by 60 min reperfusion. (3) NES+I/R group, non-excitatory electrical stimulation (NES) was commenced from 15 min before coronary artery occlusion till the end of reperfusion. (4) I/R+CGRP8-37 group, animals were given with CGRP8-37 (an antagonist of CGRP receptor, 10(-7) mol/L, 0.3 ml, i.v.) at 5 min before reperfusion without any electrical stimulation. The hemodynamics and electrocardiogram were monitored and recorded. Infarct size and troponin I were examined and CGRP expression in the myocardium and serum was analyzed. It was found that the infarct size and TnI were significantly reduced in NES+I/R group, by 45% and 58% respectively, accompanied by an obvious fall back of CGRP in myocardium, compared to I/R group (all p<0.05). Treatment with CGRP8-37 resulted in the same protection on myocardium as NES did. No significant difference in hemodynamics or ventricular tachycardia was detected among the groups (all p>0.05). It can be concluded that NES reduced the infarction size after acute myocardial ischemia and reperfusion, for which the underlying mechanism may be associated with modulation of endogenous CGRP in myocardium. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Galectin-3 is expressed in the myocardium very early post-myocardial infarction.

    PubMed

    Hashmi, Satwat; Al-Salam, Suhail

    2015-01-01

    Galectin-3 (GAL-3) plays a regulatory role in several diverse biological processes and disease states. It is associated with heart failure and increased risk of death in a number of studies. We aim to study the direct effects of ischemia on GAL-3 levels in the heart very early in the course of events following myocardial infarction (MI). Male C57B6/J mice were used for permanently ligating the left anterior descending artery of the heart to create ischemia/infarction in the anterior wall of left ventricle (LV). Heart samples were processed for immunohistochemical and immunofluorescent labeling, enzyme-linked immunosorbent assay, and quantitative reverse transcriptase polymerase chain reaction to identify GAL-3 levels in the heart during the first 24 h following MI. GAL-3 mRNA was significantly increased at 60min (P=.032), 4 h (P=.012), and 24 h (P=.00) post-MI groups in the infarcted LV as compared to sham. Thirty minutes post-MI GAL-3 mRNA is higher than the sham and almost reaching statistical significance (P=.056). GAL-3 protein was significantly increased in the LV at 30 min (P=.021), 60 min (P=.029), 4 h (P=.015), and 24 h (P=.01) post-MI compared to corresponding sham-operated mice. Plasma GAL-3 levels are also significantly raised at 24-h post-MI. GAL-3 is colocalized with cardiomyocytes and endothelial cells in the ischemic area of the LV. GAL-3 is also colocalized with hypoxia-inducible factor-1 alpha (HIF-1α). We show for the first time that GAL-3 is increased at both transcriptional and translational levels in the LV in early ischemic period, which can possibly be a part of the prosurvival gene expression profile transcribed by HIF-1α. This is significant because it can help in understanding the mechanism of very early response of the myocardium following acute infarction and help devise ways to save the viable tissue before permanent damage sets in. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. [Emoxipin in reperfusion of ischemic myocardium in dogs: effects on infarct size and plasma creatine kinase activity].

    PubMed

    Konorev, E A; Polumiskov, V Iu; Avilova, O A; Golikova, A P

    1990-09-01

    The effects of synthetic antioxidant emoxypine on infarct size and plasma creatine kinase (CK) activity was studied on open-chest anesthetized dogs with 180-min myocardial ischemia followed by reperfusion. Emoxypine (10 and 40 mg/kg) was injected intravenously, beginning since 120th min of coronary artery occlusion. Emoxypine (10 mg/kg) resulted in infarct size limitation and reduction in plasma CK activity. An increase in dose of emoxypine to 40 mg/kg largely attenuated its protective effect on infarct size. CK activity during post-ischemic reperfusion was even higher in emoxypine (40 mg/kg) group compared with control. Augmented CK leakage from irreversibly injured myocardium to plasma under these experimental conditions may be owing to preservation of microvascular integrity and improving of drainage of infarcted tissue exerted by emoxypine.

  3. Effect of ramipril on the electrophysiological characteristics of ventricular myocardium after myocardial infarction in rabbits.

    PubMed

    Zhong, Ya; Cao, Ping; Tong, Chuanfeng; Li, Xia

    2012-05-01

    The current study aims to explore the effect of ramipril on the occurrence of ventricular arrhythmias and its possible mechanism after myocardial infarction (MI) in rabbits. A total of 24 rabbits were divided into three groups: the sham operation group (SHAM), the MI group, and the ramipril group (RAM). All groups were subjected to thoracotomy under sterile conditions; the MI and RAM groups underwent ligation of the left anterior descending coronary artery. On the second day after surgery, the RAM group was given ramipril (1 mg/kg per day). The rabbits in each group were fed for 12 weeks. The monophasic action potentials of the epicardium, mid-myocardium and endocardium in each group were, respectively, recorded before the MI and at 12 weeks after the MI. Meanwhile, the episodes of ventricular tachycardia or fibrillation (VT/VF) induced by procedure stimulations were counted, and the changes in L-type Ca flux (Ica-L) were recorded by means of the whole-cell patch-clamp technique. The episodes of VT/VF were decreased in the RAM group after MI. At 12 weeks after MI, the transmural dispersion of repolarization (TDR) in the MI group was prolonged significantly compared with the SHAM and RAM groups. The density of Ica-L in the MI group was significantly lower than that any other group. Ramipril manifestly decreases the incidence of VT/VF after MI in rabbits, and the mechanism may be associated with its inhibitory effect on electrical remodeling after MI.

  4. The endothelial nitric oxide synthase cofactor tetrahydrobiopterin shields the remote myocardium from apoptosis after experimental myocardial infarction in vivo.

    PubMed

    Heidrich, Felix M; Jercke, Marcel C; Ritzkat, Anna; Ebner, Annette; Poitz, David M; Pfluecke, Christian; Quick, Silvio; Speiser, Uwe; Simonis, Gregor; Wäßnig, Nadine K; Strasser, Ruth H; Wiedemann, Stephan

    2017-08-23

    Following myocardial infarction (MI), apoptosis occurs early in the remote myocardium and contributes to the processes of myocardial remodeling. Increased nitrosative stress is a well-known and potent inductor of myocardial apoptosis. Excess activation of endothelial nitric oxide synthase (eNOS) increases its uncoupling potential and results in nitrosative stress via formation of peroxynitrite. However, the pathophysiologic role of eNOS signaling in the remote myocardium after MI is as yet undefined. The impact of eNOS activation on pro- and anti-apoptotic signaling in the remote myocardium and the influence of pretreatment with the eNOS cofactor tetrahydrobiopterin (BH4) on eNOS activation, nitrosative stress level and apoptosis induction and execution were studied in a rat myocardial infarction model in vivo. 24 hours after anterior MI, eNOS activity in animals treated with left anterior descending coronary artery ligation (LIG) significantly increased in the posterior left ventricular myocardium as did protein nitrosylation when compared to sham treatment. This was paralleled by induction of apoptosis via both, the extrinsic and intrinsic pathways. Moreover, anti-apoptotic signaling via protein kinase B/Akt and glycogen synthase-kinase 3 beta was suppressed. Notably, pretreatment with the eNOS cofactor BH4 reduced eNOS activation, prevented excess protein nitrosylation, blunted apoptosis induction, facilitated anti-apoptotic signaling and eventually prevented apoptosis execution. Here we showed that 24 hours after experimental MI in rats in vivo, apoptosis was induced in the posterior non-infarcted LV wall. Evidence is presented that pretreatment with the eNOS cofactor BH4 resulted in less nitrosative stress and weakened apoptotic processes, although stabilizers contained did participate in this phenomenon. Because apoptosis is a crucial component of myocardial remodeling, influencing eNOS signaling might be an interesting pharmacological target for the

  5. Effect of exercise training and myocardial infarction on force development and contractile kinetics in isolated canine myocardium.

    PubMed

    Canan, Benjamin D; Haizlip, Kaylan M; Xu, Ying; Monasky, Michelle M; Hiranandani, Nitisha; Milani-Nejad, Nima; Varian, Kenneth D; Slabaugh, Jessica L; Schultz, Eric J; Fedorov, Vadim V; Billman, George E; Janssen, Paul M L

    2016-04-15

    It is well known that moderate exercise training elicits a small increase in ventricular mass (i.e., a physiological hypertrophy) that has many beneficial effects on overall cardiac health. It is also well known that, when a myocardial infarction damages part of the heart, the remaining myocardium remodels to compensate for the loss of viable functioning myocardium. The effects of exercise training, myocardial infarction (MI), and their interaction on the contractile performance of the myocardium itself remain largely to be determined. The present study investigated the contractile properties and kinetics of right ventricular myocardium isolated from sedentary and exercise trained (10-12 wk progressively increasing treadmill running, begun 4 wk after MI induction) dogs with and without a left ventricular myocardial infarction. Exercise training increased force development, whereas MI decreased force development that was not improved by exercise training. Contractile kinetics were significantly slower in the trained dogs, whereas this impact of training was less or no longer present after MI. Length-dependent activation, both evaluated on contractile force and kinetics, was similar in all four groups. The control exercise-trained group exhibited a more positive force-frequency relationship compared with the sedentary control group while both sedentary and trained post-MI dogs had a more negative relationship. Last, the impact of the β-adrenergic receptor agonist isoproterenol resulted in a similar increase in force and acceleration of contractile kinetics in all groups. Thus, exercise training increased developed force but slowed contractile kinetics in control (noninfarcted animals), actions that were attenuated or completely absent in post-MI dogs. Copyright © 2016 the American Physiological Society.

  6. Macrocyclic contrast agents for magnetic resonance imaging of chronic myocardial infarction: intraindividual comparison of gadobutrol and gadoterate meglumine.

    PubMed

    Wagner, Moritz; Schilling, Rene; Doeblin, Patrick; Huppertz, Alexander; Luhur, Reny; Schwenke, Carsten; Maurer, Martin; Hamm, Bernd; Taupitz, Matthias; Durmus, Tahir

    2013-01-01

    To compare 0.15 mmol/kg gadobutrol for late gadolinium enhancement (LGE) imaging of chronic myocardial infarction with a relaxivity-adjusted dose of gadoterate meglumine (Gd-DOTA). Seventeen patients with suspected chronic myocardial infarction underwent LGE imaging at 1.5 T, acquiring an inversion-recovery-prepared gradient echo sequence 15 min after contrast agent administration. Each patient underwent LGE imaging twice, once after administration of 0.15 mmol/kg gadobutrol (r1 = 5.2 l mmol(-1) s(-1)) and after 0.22 mmol/kg Gd-DOTA (r1 = 3.6 l mmol(-1) s(-1)). Two readers independently determined infarct size and contrast-to-noise ratios of infarcted myocardium to remote myocardium (CNR(remote)) and to the left ventricular lumen (CNR(lumen)). LGE was present in 14 patients. Infarct sizes determined after administration of gadobutrol [23.4 ml; 95 % CI (14.4; 32.5)] and Gd-DOTA [22.1 ml; 95 % CI (13.0; 31.1)] were not statistically different (P = 0.22). The CNR(remote) of LGE in infarcted myocardium on gadobutrol- and Gd-DOTA-enhanced images was 44.1 [95 % CI (31.0; 57.1)] and 45.2 [95 % CI (32.2; 58.3)], respectively (P = 0.73). CNR(lumen) was significantly higher on gadobutrol-enhanced LGE images [12.7; 95 % CI (2.5; 23.0) versus 6.8; 95 % CI (-3.5; 17.0); P = 0.02]. At relaxivity-adjusted doses, gadobutrol and Gd-DOTA yielded similar infarct sizes with superior contrast between infarcted myocardium and left ventricular lumen on gadobutrol-enhanced images.

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

    PubMed Central

    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. PMID:25429216

  8. Postinfarct active cardiac-targeted delivery of erythropoietin by liposomes with sialyl Lewis X repairs infarcted myocardium in rabbits.

    PubMed

    Yamada, Yoshihisa; Kobayashi, Hiroyuki; Iwasa, Masamitsu; Sumi, Shohei; Ushikoshi, Hiroaki; Aoyama, Takuma; Nishigaki, Kazuhiko; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi; Kiso, Makoto; Minatoguchi, Shinya

    2013-04-15

    We investigated the effect of cardiac-targeting erythropoietin (EPO)-encapsulated liposomes with sialyl Lewis(X) (SLX) on myocardial infarct (MI) size, left ventricular (LV) remodeling and function, and its molecular mechanism for repairing infarcted myocardium. In rabbits, MI was induced by 30 min of coronary occlusion followed by reperfusion. EPO-encapsulated liposomes with SLX (L-EPO group), EPO-encapsulated liposomes without SLX (L-EPO without SLX group), liposomes with SLX without EPO (L group), or saline (saline group) were intravenously administered immediately after MI. MI sizes and numbers of microvessels were assessed 14 days after MI. Prosurvival proteins and signals were assessed by Western blot analysis 2 and 14 days after MI. Confocal microscopy and electron microscopy showed the specific accumulation of liposomes with SLX in the infarcted myocardium. MI and cardiac fibrosis areas were significantly smaller in the L-EPO group than in the other groups. LV function and remodeling were improved in the L-EPO group. The number of CD31-positive microvessels was significantly greater in the L-EPO group than in the other groups. Higher expressions of EPO receptors, phosphorylated (p)Akt, pERK, pStat3, VEGF, Bcl-2, and promatrix metalloproteinase-1 were observed in the infarct area in the L-EPO group than in the other groups. EPO-encapsulated liposomes with SLX selectively accumulated in the infarct area, reduced MI size, and improved LV remodeling and function through activation of prosurvival signals and by exerting antifibrotic and angiogenic effects. EPO-encapsulated liposomes with SLX may be a promising strategy for active targeting treatment of acute MI.

  9. Prognostic Significance of Remote Myocardium Alterations Assessed by Quantitative Noncontrast T1 Mapping in ST-Segment Elevation Myocardial Infarction.

    PubMed

    Reinstadler, Sebastian J; Stiermaier, Thomas; Liebetrau, Johanna; Fuernau, Georg; Eitel, Charlotte; de Waha, Suzanne; Desch, Steffen; Reil, Jan-Christian; Pöss, Janine; Metzler, Bernhard; Lücke, Christian; Gutberlet, Matthias; Schuler, Gerhard; Thiele, Holger; Eitel, Ingo

    2017-06-09

    This study assessed the prognostic significance of remote zone native T1 alterations for the prediction of clinical events in a population with ST-segment elevation myocardial infarction (STEMI) who were treated by primary percutaneous coronary intervention (PPCI) and compared it with conventional markers of infarct severity. The exact role and incremental prognostic relevance of remote myocardium native T1 mapping alterations assessed by cardiac magnetic resonance (CMR) after STEMI remains unclear. We included 255 consecutive patients with STEMI who were reperfused within 12 h after symptom onset. CMR core laboratory analysis was performed to assess left ventricular (LV) function, standard infarct characteristics, and native T1 values of the remote, noninfarcted myocardium. The primary endpoint was a composite of death, reinfarction, and new congestive heart failure within 6 months (major adverse cardiac events [MACE]). Patients with increased remote zone native T1 values (>1,129 ms) had significantly larger infarcts (p = 0.012), less myocardial salvage (p = 0.002), and more pronounced LV dysfunction (p = 0.011). In multivariable analysis, remote zone native T1 was independently associated with MACE after adjusting for clinical risk factors (p = 0.001) or other CMR variables (p = 0.007). In C-statistics, native T1 of remote myocardium provided incremental prognostic information beyond clinical risk factors, LV ejection fraction, and other markers of infarct severity (all p < 0.05). The addition of remote zone native T1 to a model of prognostic CMR parameters (ejection fraction, infarct size, and myocardial salvage index) led to net reclassification improvement of 0.82 (95% confidence interval: 0.46 to 1.17; p < 0.001) and to an integrated discrimination improvement of 0.07 (95% confidence interval: 0.02 to 0.13; p = 0.01). In STEMI patients treated by PPCI, evaluation of remote zone alterations by quantitative noncontrast T1 mapping provided independent

  10. Reduced microvascular density in non-ischemic myocardium of patients with recent non-ST-segment-elevation myocardial infarction.

    PubMed

    Campbell, Duncan J; Somaratne, Jithendra B; Jenkins, Alicia J; Prior, David L; Yii, Michael; Kenny, James F; Newcomb, Andrew E; Kelly, Darren J; Black, Mary Jane

    2013-08-10

    Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers. We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD. Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients. Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Diagnostic usefulness of the oedema-infarct ratio to differentiate acute from chronic myocardial damage using magnetic resonance imaging.

    PubMed

    Yamada, Kiyoyasu; Isobe, Satoshi; Suzuki, Susumu; Kinoshita, Kousuke; Yokouchi, Kazuhiko; Iwata, Hirokazu; Ohshima, Satoru; Hirai, Makoto; Sawada, Ken; Murohara, Toyoaki

    2012-04-01

    To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. MR can differentiate reversible from irreversible myocardial damage after myocardial infarction. MR is a useful modality to noninvasively differentiate the infarct stages. The O/I is an important index to decide therapeutic strategies.

  12. Adult bone marrow-derived cells do not acquire functional attributes of cardiomyocytes when transplanted into peri-infarct myocardium.

    PubMed

    Scherschel, John A; Soonpaa, Mark H; Srour, Edward F; Field, Loren J; Rubart, Michael

    2008-06-01

    The cardiomyogenic potential of adult bone marrow (BM) cells after being directly transplanted into the ischemically injured heart remains a controversial issue. In this study, we investigated the ability of transplanted BM cells to develop intracellular calcium ([Ca(2+)](i)) transients in response to membrane depolarization in situ. Low-density mononuclear (LDM) BM cells, c-kit-enriched (c-kit(enr)) BM cells, and highly enriched lin(-) c-kit(+) BM cells were obtained from adult transgenic mice ubiquitously expressing enhanced green fluorescent protein (EGFP), and injected into peri-infarct myocardiums of nontransgenic mice. After 9-10 days the mice were killed, and the hearts were removed, perfused in Langendorff mode, loaded with the calcium-sensitive fluorophore rhod-2, and subjected to two-photon laser scanning fluorescence microscopy (TPLSM) to monitor action potential-induced [Ca(2+)](i) transients in EGFP-expressing donor-derived cells and non-expressing host cardiomyocytes. Whereas spontaneous and electrically evoked [Ca(2+)](i) transients were found to occur synchronously in host cardiomyocytes along the graft-host border and in areas remote from the infarct, they were absent in all of the >3,000 imaged BM-derived cells that were located in clusters throughout the infarct scar or peri-infarct zone. We conclude that engrafted BM-derived cells lack attributes of functioning cardiomyocytes, calling into question the concept that adult BM cells can give rise to substantive cardiomyocyte regeneration within the infarcted heart.

  13. Lack of effect of prior training on subsequent ischaemic and infarcting myocardium and collateral development in dogs with normal hearts.

    PubMed

    Cohen, M V; Steingart, R M

    1987-04-01

    To determine whether exercise training in animals with normal coronary arteries has a salutary effect on ischaemic myocardium, 24 dogs were randomly assigned to be either trained or confined to cages for three months. All dogs then underwent left thoracotomy for placement of indwelling right and left atrial and aortic catheters and a loose snare ligature around the proximal left circumflex coronary artery. Three days after operation control scintigrams were recorded after injection of thallous chloride-201 in animals running on a treadmill to achieve exercise heart rates of 220 beats.min-1. Four days later the snares were pulled to occlude the left circumflex artery and infarct size determined by measuring venous activity of creatine phosphokinase. Three days after infarction the first post-ligation scintigram was performed after thallium-201 injection in exercising animals. Exercise scans were repeated at 10 days and 2, 4, and 6 weeks after coronary ligation. During the final exercise study collateral blood flow was measured with radioactive microspheres. There was no difference in mean creatine phosphokinase appearance time, peak creatine phosphokinase activity, or measured infarct size between the trained and sedentary dogs. The ratio of thallium-201 activity in left circumflex artery or ischaemic area to left anterior descending artery or normally perfused myocardium fell from 100% before occlusion to 86.6% in the sedentary animals and 80.6% in the trained dogs three days after coronary ligation. Although these falls were significant (p less than 0.025 and p less than 0.005 respectively), there was no difference between groups. Over the next five and a half weeks the scintigraphic defect shrank as the thallium-201 ratio gradually increased, but changes were again similar in both groups. At six weeks there was little difference in exercise collateral flow to left circumflex artery myocardium and flow to normal myocardial tissue in cage confined and trained dogs

  14. Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

    PubMed

    Choo, Eun Ho; Lee, Jun-Ho; Park, Eun-Hye; Park, Hyo Eun; Jung, Nam-Chul; Kim, Tae-Hoon; Koh, Yoon-Seok; Kim, Eunmin; Seung, Ki-Bae; Park, Cheongsoo; Hong, Kwan-Soo; Kang, Kwonyoon; Song, Jie-Young; Seo, Han Geuk; Lim, Dae-Seog; Chang, Kiyuk

    2017-04-11

    Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases. We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation. In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue-specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival. This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair. © 2017 American Heart Association, Inc.

  15. Improving the efficacy of therapeutic angiogenesis by UTMD-mediated Ang-1 gene delivery to the infarcted myocardium.

    PubMed

    Deng, Qing; Hu, Bo; Cao, Sheng; Song, Hong-Ning; Chen, Jin-Ling; Zhou, Qing

    2015-08-01

    This study aimed to verify the feasibility and efficacy of ultrasound-targeted microbubble destruction (UTMD)-mediated angiopoietin-1 (Ang-1) gene delivery into the infarcted myocardium. Microbubbles carrying anti-intercellular adhesion molecule-1 (ICAM-1) antibody were prepared and identified. The microbubbles carrying anti-ICAM-1 antibody selectively adhered to the interleukin (IL)-1β-stimulated ECV304 cells and to the ischemic vascular endothelium, and the infarct area was examined to evaluate the targeting ability of ICAM-1 microbubbles in vitro and in vivo. The intravenous administration of the Ang-1 gene was carried out by UTMD in rabbits with acute myocardial infarction (AMI). The rabbits were divided into the control (no treatment), non-targeted microbubble destruction (non-TMB) and the ICAM-1 TMB (TMB) group. Gene delivery by direct intramyocardial injection (IMI) served as a reference. Two weeks later, regional myocardial perfusion and cardiac function were evaluated by echocardiography, and Ang-1 gene-mediated angiogenesis was assessed histologically and biochemically. The results revealed that the ICAM-1-targeted microbubbles selectively adhered to the IL-1β-stimulated ECV304 cells in vitro and to the ischemic vascular endothelium in the infarct area of the rabbits with AMI. Two weeks after the delivery of the Ang-1 gene, compared with the non-TMB group, left ventricular function and myocardial perfusion at the infarct area had improved in the TMB and IMI group (p<0.01). Ang-1 gene expression was detectable in the non-TMB, TMB and IMI group, while its expression was higher in the latter 2 groups (all p<0.01). The microvascular density (MVD) of the infarct area in the non-TMB, TMB and IMI group was 65.6 ± 4.4, 96.7 ± 2.1 and 100.7 ± 3.6, respectively (p<0.01). The findings of our study indicate that UTMD-mediated gene delivery may be used to successfully deliver the Ang-1 gene to the infarcted myocardium, thus improving the efficacy of therapeutic

  16. Detection of residual jeopardized myocardium 3 weeks after myocardial infarction by exercise testing with thallium-201 mycardial scintigraphy

    SciTech Connect

    Turner, J.D.; Schwartz, K.M.; Logic, J.R.; Sheffield, L.T.; Kansal, S.; Roitman, D.I.; Mantle, J.A.; Russell, R.O.; Rackley, C.E.; Rogers, W.J.

    1980-04-01

    The usefulness of thallium-201 (Tl-201) exercise myocardial scintigraphy in identifying patients with multivessel coronary artery disease (MVCAD) and residual jeopardized myocardium after myocardial infarction (MI) was evaluated in 32 patients 3 weeks after MI. All patients underwent (1) limited multilead submaximal treadmill testing, (2) thallium-201 (Tl) myocardial scintigraphy at end-exercise and at rest, and (3) coronary and left ventricular angiography. Tl-201 perfusion defects were categorized as either reversible (ischemia) or irreversible (scar). The conventional exercise test was designated positive if there was ST depression > = 1mm and/or angina. Jeopardized myocardium (JEP) was defined angiographically as a segment of myocardium with normal or hypokinetic wall motion supplied by a significantly stenotic major coronary artery. MVCAD was defined as two or more significantly stenotic coronary arteries. Significant coronary stenosis was categorized as either 50 to 69% diameter narrowing or > = 70% diameter narrowing, thereby yielding, respectively, two subgroups each of jeopardized myocardium (JEP-50 and JEP-70) and MVCAD (MV-50 and MV-70). Clinical findings of angina, heart failure or ventricular arrhythmias during the late convalescent period after MI occurred in four of 10 patients (40%) with MV-50, five of 16 (31%) with MV-70, four of 10 (40%) with JEP-50 and five of 18 (28%) with JEP-70, and thus were insensitive for detecting MVCAD and JEP. Reversible ischemia and/or a positive conventional exercise test occurred in five of 10 patients (50%) with MV-50, 13 of 16 (81%) with MV-70, four of 10 (40%) with JEP-50 and 15 of 18 (83%) with JEP-70. All eight patients with both Tl-201 reversible ischemia and a positive conventional exercise test had JEP-70. In 30 of 31 patients (97%) with angiographic asynergy, Tl-201 scar was detected. No complications were associated with exercise testing.

  17. [Effect of medicines for activating blood and reinforcing Qi on angiogenesis in infarcted myocardium edge area of acute myocardial infarction model in rats].

    PubMed

    Zang, Wen-Hua; Yin, Shen-Hua; Tang, De-Cai; Li, Bing-Bing

    2014-03-01

    To study the effect of medicines for activating blood and reinforcing Qi on the number of new micro-vessels and the protein expressions of VEGF and bFGF in the infarcted myocardium edge area of acute myocardial infarction (AMI) model in rats. The AMI model of rats was established. After the successful model establishment, rats were randomly divided into the sham-operated group, the model group, the Danshen-Huangqi (1 : 2) group, the Danshen-Huangqi (1 : 1) group, the Chuanxiong-Huangqi (1 : 2) group, the Danshen group, the Chuanxiong group, the Chishao group and the Shexiang Baoxin pill group, with five rats in each group. Rats in each medicated group were orally administered with drugs as per 13.5 g x kg(-1) x d(-1) once everyday for three weeks. The immunohistochemical SP method was adopted to detect the expression of vWF in myocardial tissues, and count the number of micro-vessels (MVC). The protein expression of VEGF and bFGF in myocardial tissues were determined by Western blot. The new micro-vessels stained by vWF factor could be found in the infarcted myocardium edge area of the sham-operated group, the model group and all of medicated groups. The sham-operated group show unobvious new micro-vessels in myocardial tissues. A small amount of new micro-vessels could be seen in the infarcted myocardium edge area of the model group. Whereas a larger number of micro-vessels could be seen in the infarcted myocardium edge area of all of medicated groups. The differences between the sham-operated group and the model group had statistical significance (P < 0.05). The differences between each medicated group and the model group had statistical significance as well (P < 0.05 or P < 0.01). The lowest protein expression of VEGF and bFGF was found in myocardium of the sham-operated group, with the statistical significance compared with the model group (P < 0.05). Compared with the model group, each medicated group showed significant increase in the protein expression of

  18. Porcine (Sus scrofa) Chronic Myocardial Infarction Model Development

    DTIC Science & Technology

    2015-04-03

    Myocardial Infarction Model Development.” PRINCIPAL INVESTIGATOR (PI) / TRAINING COORDINATOR (TC): Lt Col. Daren Danielson DEPARTMENT: 60MSGS/SGCH...invasively, a myocardial infarction that was isolated to the mid-anterior, left ventricular wall. In doing so, we were able to create an infarct that...be used to investigate new methodologies for treatment of chronic myocardial infarction in individuals afflicted with chronic ischemic

  19. Exercise four hour redistribution thallium-201 single photon emission computed tomography and exercise induced ST segment elevation in detecting the viable myocardium in patients with acute myocardial infarction

    PubMed Central

    Yamagishi, H; Akioka, K; Takagi, M; Tanaka, A; Takeuchi, K; Yoshikawa, J; Ochi, H

    1999-01-01

    Objective—To investigate the specificity and sensitivity of the combination of redistribution in exercise thallium-201 single photon emission computed tomography (SPECT) and exercise induced ST elevation for detecting the viable myocardium in patients with acute myocardial infarction.
Design—37 patients were studied within seven weeks of onset of Q wave myocardial infarction (anterior in 22, inferior in 15). All patients underwent exercise four hour redistribution thallium-201 SPECT and positron emission tomography using fluorine-18-fluorodeoxyglucose (FDG) and nitrogen-13 ammonia under fasting conditions.
Results—Sixteen patients showed exercise induced ST elevation ⩾ 1.5 mm, and 15 of these had increased FDG uptake in the infarct region. Eleven of 16 patients (10 of 11 patients with anterior infarctions) with irreversible thallium-201 defects and increased FDG uptake showed exercise induced ST elevation. The sensitivity, specificity, and predictive accuracy of redistribution, exercise induced ST segment elevation, or both for detecting increased FDG uptake were 82%, 75%, and 67% (94%, 75%, and 91% for anterior infarctions), respectively. 
Conclusions—In patients with acute Q wave myocardial infarction, the combination of redistribution in exercise thallium-201 SPECT and exercise induced ST elevation can detect the viable myocardium in the infarct region with high sensitivity and specificity, especially in patients with anterior infarctions.

 Keywords: acute myocardial infarction;  viability;  exercise induced ST elevation;  exercise thallium-201 SPECT PMID:10220539

  20. Effects of low-dose hydroxychloroquine on expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in peri-infarct myocardium in rats

    PubMed Central

    Zhou, Jing; Li, Gang; Wang, Zhi-Hua; Wang, Li-Ping; Dong, Pu-Jiang

    2013-01-01

    BACKGROUND: Low-dose hydroxychloroquine (HCQ) and ataxia-telangiectasia-mutated (ATM) protein kinase have recently been postulated to be beneficial for the prevention of the age-associated metabolic syndrome including hypertension, hypercholesterolemia and glucose intolerance; however, the effects of low-dose HCQ on the expression of ATM downstream phosphorylated Akt (protein kinase B) and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium remain unclear. OBJECTIVE: To explore the effects of low-dose HCQ on the expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium in a rat model. METHODS: Myocardial infarction (MI) was induced experimentally in a subset of rats, while others underwent sham operation (sham). Three days after operation, surviving Sprague-Dawley male rats were divided into MI+HCQ, MI, sham+HCQ and sham groups. MI+HCQ and sham + HCQ groups were treated with HCQ (3.4 mg/kg); and MI and sham groups were treated with phosphate buffered (ie, physiological) saline (10 mL/kg) by gavage every day for 12 weeks. The expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium was detected by Western blot and terminal deoxynucleotidyl transferase dUTP nick end labelling, respectively. RESULTS: Twelve weeks after treatment, the expression of phosphorylated Akt protein was significantly increased (P<0.05). Expression of phosphorylated p53 protein was not significantly different (P>0.05) in the peri-infarct myocardium of the MI+HCQ group from that in the MI group. The cardiomyocyte apoptosis rate in the peri-infarct myocardium was significantly decreased in the MI+HCQ group compared with the MI group (P<0.05). CONCLUSION: Low-dose HCQ can significantly increase the expression of phosphorylated Akt protein without significantly impacting expression of phosphorylated p53 protein in the peri-infarct myocardium. Accordingly, it can inhibit

  1. Analysis of post-infarction salvaged myocardium by cardiac magnetic resonance. Predictors and influence on adverse ventricular remodeling.

    PubMed

    Monmeneu, José V; Bodí, Vicente; López-Lereu, María P; Sanchis, Juan; Núñez, Julio; Chaustre, Fabián; Husser, Oliver; Merlos, Pilar; Bonanad, Clara; Miñana, Gema; Chorro, Francisco J; Llácer, Angel

    2012-07-01

    To evaluate by cardiovascular magnetic resonance those factors related to the amount of salvaged myocardium after a myocardial infarction and its value in predicting adverse ventricular remodeling. One hundred eighteen patients admitted for a first ST elevation myocardial infarction (primary angioplasty, 65 patients; a pharmacoinvasive strategy, 53 patients) underwent magnetic resonance (6 [5-8] days and 6 months; n=83). The myocardial salvage index was quantitatively assessed as the percentage of area at risk (T2-weighted sequences) not showing late enhancement. Myocardial salvage index >31% (median) was associated with a shorter time to reperfusion (153 min vs 258 min), a lower rate of diabetes (12% vs 32%), shorter time to magnetic resonance, and better cardiovascular parameters (P<.05 for all analyses). There were no significant differences depending on the reperfusion method. In a logistic regression analysis, delayed reperfusion (odds ratio=0.42 [0.29-0.63]; P<.0001), diabetes (odds ratio=0.32 [0.11-0.99]; P<.05) and a longer time to the performance of magnetic resonance (odds ratio=0.86 [0.76-0.97]; P<.05) were independently related to a lower probability of a myocardial salvage index >31%. Predictors of increased left ventricular end-systolic volume at 6 months were the number of segments showing an extent of transmural necrosis >50% (odds ratio =1.51 [1.21-1.90]; P<.0001) and left ventricular end-systolic volume at one week (odds ratio=1.12 [1.06-1.18]; P<.0001). Cardiovascular magnetic resonance enables the quantification of the salvaged myocardium after myocardial infarction. The celerity with which reperfusion therapy is administered constitutes its most important predictor. The possible effect of a delay in the performance of magnetic resonance on myocardial salvage needs to be confirmed. Salvaged myocardium does not improve the value of magnetic resonance for predicting adverse remodeling. Copyright © 2012 Sociedad Española de Cardiolog

  2. Myocardium and microvessel endothelium apoptosis at day 7 following reperfused acute myocardial infarction.

    PubMed

    Kang, Sheng; Yang, Yue-jin; Wu, Yi-ling; Chen, Yu-tong; Li, Li; Tian, Yi

    2010-01-01

    This study was to investigate the salvaged myocardial and microvascular endothelial cells apoptosis at the first week of reperfused acute myocardial infarction (AMI). Sixteen mini swines (20-30 kg) were randomly assigned to the sham-operated group and the AMI group. The acute myocardial infarction and reperfusion model was created, and pathologic myocardial tissue was collected at day 7 following left anterior descending coronary artery reperfusion, and detected by transmission electron microscope, in situ cell apoptosis detection (TUNEL method), Real-time Quantitative Polymerase Chain Reaction and Western blot. In the AMI group, the infarcted area showed the myolysis, fibroblast and injuried endothelial cells under transmission electron microscope. The infarcted area had higher apoptotic index of microvascular endothelial cells than the marginal area, the normal area, and the sham-operated area (all P<0.05). Fas and Bax mRNA expressions in the infarcted area were higher than those in the marginal area, the normal area, and the sham-operated area (all P<0.05), and both protein overexpressions and Bcl-2 low expression in the infarcted and marginal areas compared with the normal area and the sham-operated area. The overexpressions of Fas and Bax or the low expression of Bcl-2 in the infarcted and marginal heart tissue may play an important role in the acceleration of myocardial and endothelial apoptosis at 7th day following reperfused acute myocardial infarction. Copyright 2009 Elsevier Inc. All rights reserved.

  3. Chronic catecholamine depletion switches myocardium from carbohydrate to lipid utilisation.

    PubMed

    Drake-Holland, A J; Van der Vusse, G J; Roemen, T H; Hynd, J W; Mansaray, M; Wright, Z M; Noble, M I

    2001-03-01

    Chronic cardiac transplantation denervation (i.e., global sympathetic denervation with myocardial catecholamine depletion, plus parasympathetic denervation) is known to inhibit myocardial oxidation of glucose. It is not known whether this is due to increased utilization of lactate, lipid or ketone bodies. The purpose of the present study was to test the hypothesis that the extraction and contribution of blood-borne fatty acids (FA) to overall oxidative energy conversion is increased. In anaesthetised dogs (control n = 6, cardiac denervated n = 6), we investigated fatty acid (FA) utilization. The studies were made at least four weeks after surgical cardiac denervation. Measurements were made of total FAs and with a radio-labelled tracer (U-14C palmitate). The contribution of FA utilisation to overall substrate oxidation rose from 31% (control) to 48% (cardiac denervated). The increase in the ratio (%) of CO2 production from palmitate oxidation to total CO2 production increased from 4.0 +/- 1.8 (control) to 10.6 +/- 5.8 (denervated, p = 0.04). The time from uptake of FA to release of CO2 product was unaltered. We conclude that the contribution of FA oxidation to overall energy conversion is increased in chronically denervated hearts, which is postulated to result from a decline in the active form of pyruvate dehydrogenase. This would appear to be a result of chronic catecholamine depletion.

  4. Angiographic validation of magnetic resonance assessment of myocardium at risk in non-ST-elevation myocardial infarction.

    PubMed

    Buckert, Dominik; Mariyadas, Manuela; Walcher, Thomas; Rasche, Volker; Wöhrle, Jochen; Rottbauer, Wolfgang; Bernhardt, Peter

    2013-08-01

    In the setting of acute myocardial ischemia, the hypoperfused portion of the myocardium is in danger of becoming irreversibly injured. This portion is called the area at risk (AAR). It is of clinical interest to be able to estimate the AAR for further evaluation and improvement of different revascularization strategies. The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) has been shown to be a jeopardy score with a good performance for angiographic assessment of the myocardium supplied by a coronary vessel, representing the AAR. Recently, cardiac magnetic resonance imaging (CMR) has been demonstrated to also provide good results in determining the AAR, especially in the setting of acute ST-elevation infarction patients. Therefore, the aim of our trial was to compare T2-weighted CMR imaging for assessment of AAR in patients with non-ST-elevation myocardial infarction (NSTEMI) and to validate this approach against the angiographic APPROACH-score. We enrolled sixty-four patients presenting with acute NSTEMI that underwent coronary X-ray angiography within 72 h of symptom onset. Two blinded readers performed offline angiographic AAR assessment using the modified APPROACH-score, as being described elsewhere. Furthermore, with the use of a semi-automatic T2w-CMR approach, the AAR was quantified by two fully blinded readers. The resulting mean AAR determined by the modified APPROACH-score was 28.6 ± 10.0 %. The mean CMR derived AAR was 27.6 ± 12.7 %. CMR assessment tended to slightly underestimate the AAR in comparison to angiographic scoring (difference -0.09 ± 7.6 %). There is a good correlation between the AAR assessed by CMR and by angiography (r = 0.65, p < 0.001). T2-weigthed CMR is able to quantify the AAR with very good correlation to the angiographic APPROACH-score in NSTEMI patients.

  5. Towards on line monitoring the evolution of the myocardium infarction scar with an implantable electrical impedance spectrum monitoring system.

    PubMed

    Sanchez, B; Guasch, A; Bogonez, P; Galvez, C; Puig, V; Prat, C; Semino, C E; Bayes-Genis, A; Bragos, R

    2012-01-01

    The human heart tissue has a limited capacity for regeneration. Tissue and cellular therapies based on the use of stem cells may be useful alternatives to limit the size of myocardial infarction. In this paper, the preliminary results from an experimental campaign for on-line monitoring of myocardium scar infarction are presented. This study has been carried out under a research project that has as main objective the development and application of a bioactive patch implant for regeneration of myocardial infarction. Electrical Impedance Spectroscopy (EIS) has been chosen as a tissue state monitoring technique. What is presented in this communication is the first results of an implantable EIS measurement system which has been implanted in a subset of the animals corresponding to the control group, along one month. In all the animals, the myocardial infarction was induced by the ligation of the first circumflex marginal artery. In the animal group presented, the bioactive patch scaffold and the electrodes were implanted without the stem cells load. The scaffold is a piece of decellularized human pericardium, lyophilized and rehydrated with hydrogel RAD16-I. Nanogold particles were also placed near the electrodes to improve the electrode area conductivity. The results presented correspond to the subset of animals (n = 5), which had implanted the bioimpedance system monitoring the electrical impedance spectrum in vivo during 1 month. Two electrodes were connected to the bioactive patch implant. A total of 14 logarithmically spaced frequencies were measured every 5 minutes, from 100 Hz to 200 kHz. Results show a convergence of low-frequency and high frequency impedance magnitudes along the measurement period, which is coherent with the scar formation.

  6. Genetic modification of stem cells for improved therapy of the infarcted myocardium.

    PubMed

    Haider, Husnain Kh; Mustafa, Anique; Feng, Yuliang; Ashraf, Muhammad

    2011-10-03

    The conventional treatment modalities for ischemic heart disease only provide symptomatic relief to the patient without repairing and regenerating the damaged myocardium. Stem cell transplantation has emerged as a promising alternative therapeutic approach for cardiovascular diseases. Stem cells possess the potential of differentiation to adopt morphofunctional cardiac and vasculogenic phenotypes to repopulate the scar tissue and restore regional blood flow in the ischemic myocardium. These beneficial therapeutic effects make stem cell transplantation the method of choice for the treatment of ischemic heart disease. The efficacy of stem cell transplantation may be augmented by genetic manipulation of the cells prior to transplantation. Not only will insertion of therapeutic transgene(s) into the stem cells support the survival and differentiation of cells in the unfavorable microenvironment of the ischemic myocardium, but also the genetically manipulated stem cells will serve as a source of the transgene expression product in the heart for therapeutic benefits. We provide an overview of the extensively studied stem cell types for cardiac regeneration, the various methods in which these cells have been genetically manipulated and rationale of genetic modification of stem cells for use in regenerative cardiovascular therapeutics.

  7. Effects of xuesetong soft capsules on angiogenesis and VEGF mRNA expression in ischemic myocardium in rats with myocardial infarction.

    PubMed

    Wang, Zhen-Tao; Zhang, Shu-Juan; Han, Li-Hua; Chai, Song-Bo

    2012-03-01

    To observe the effects of Xuesetong Soft Capsules, Notoginseng total saponin) on angiogenesis and vascular endothelial growth factor (VEGF) mRNA expression in ischemic myocardium of rats with myocardial infarction. The left coronary artery of rats was ligated to establish the animal model of acute myocardial infarction. Rats were randomly divided into Xuesetong Soft Capsule, Shexiangbaoxin Pill (positive control), model (negative control) and sham operation groups. After 6 weeks, microvessel count (MVC), microvessel density (MVD) and VEGF mRNA expression in ischemic myocardium were evaluated. MVC and MVD in the myocardial infarct border area in model, Shexiangbaoxin Pill and Xuesetong Soft Capsule groups significantly increased compared with those of the sham operation group (P < 0.05). MVC and MVD in the myocardial infarct border area in Xuesetong Soft Capsule and Shexiangbaoxin Pill groups significantly increased compared with those of the model group (P < 0.05). No significant differences between Xuesetong Soft Capsule and Shexiangbaoxin Pill groups were observed (P > 0.05). The model group showed significantly higher VEGF mRNA expression than that in the sham operation group (P < 0.05). Xuesetong Soft Capsule and Shexiangbaoxin Pill groups showed significantly higher VEGF mRNA expression than that of the model group (P < 0.05). No significant difference between Xuesetong Soft Capsule and the Shexiangbaoxin Pill groups was observed (P > 0.05). Xuesetong Soft Capsules promote angiogenesis in ischemic myocardium after myocardial infarction and the mechanism may be associated with VEGF mRNA expression.

  8. uPA, uPAR and TGFβ₁ expression during early and late post myocardial infarction period in rat myocardium.

    PubMed

    Stavropoulou, Anastasia; Philippou, Anastassios; Halapas, Antonios; Sourla, Antigone; Pissimissis, Nikolaos; Koutsilieris, Michael

    2010-01-01

    The expression patterns of transforming growth factor beta 1 (TGFβ₁), urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) were analysed after artery ligation-induced myocardial infarction (MI) in the rat myocardium. uPA and uPAR expressions were significantly increased both at transcriptional and protein level during early phase post MI period (uPA at 1 hour and uPAR at 24 hours post infarction). TGFβ1 mRNA expression profile revealed a significant increase of TGFβ1 expression from day 4 up to 8 weeks post infarction. These data suggest that the need for an increasing TGFβ₁ bioavailability during the post-infarction period in rat myocardium is achieved in the early post MI period by an increased expression of uPA/uPAR proteolytic system (indirect activation of latent TGFβ₁) and in the late post MI period by direct regulation of TGFβ₁ expression. It is therefore concluded that differential regulation of the TGFβ₁ bioavailability may be a crucial step of the repair mechanisms during the post MI infarction period in the rat myocardium.

  9. Effects of acute and chronic uremia on active cation transport in rat myocardium

    SciTech Connect

    Druml, W.; Kelly, R.A.; England, B.K.; O'Hara, D.S.; Mitch, W.E. )

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  10. Blockade of spinal nerves inhibits expression of neural growth factor in the myocardium at an early stage of acute myocardial infarction in rats.

    PubMed

    Yue, W; Guo, Z

    2012-09-01

    Neural growth factor (NGF) is required for healing and sprouting of cardiac sympathetic and sensory nerves and plays important roles in cardiac protection, sustaining cardiac function and regeneration in ischaemic heart disease. The overexpression or lack of the NGF could be harmful to the heart. In this study, we examined the role of spinal nerves in the modulation of expression of the NGF in the myocardium at risk of ischaemia soon after acute myocardial infarction in rats. Coronary artery occlusion (CAO) was carried out in anaesthetized rats with and without preconditioning of blockade of the spinal nerves. The expression of the NGF protein and mRNA in the myocardium at risk of ischaemia was examined using immunohistochemical assay, enzyme-linked immunosorbent assay, and real-time quantitative reverse transcription polymerase chain reaction assay. In the left ventricle, immunoreactive cells and fibre-like structures were mainly located in the myocardium and in the epicardium. The NGF protein expression was increased by two-fold in the myocardium at risk of ischaemia during the 60 min of CAO, while the NGF mRNA was up-regulated three-fold, at 360 min after acute myocardial infarction. The blockade of the spinal nerves completely abolished the up-regulation of the NGF in the myocardium (P<0.05). The spinal nerves innervating the heart may play an important role in sustaining the up-regulation of the NGF in the myocardium early after acute myocardial infarction, an effect which can be inhibited by the blockade of these nerves.

  11. Remodeling of myocardium in rat with chronic dyslipidemia and under conditions of verapamil treatment.

    PubMed

    Klinnikova, M G; Yuzhik, E I; Pichigin, V I; Lushnikova, E L

    2014-11-01

    The type and intensity of remodeling (structural reorganization) of the myocardium in Wistar rats were studied under conditions of experimental chronic dyslipidemia and verapamil treatment. Long (64 days) atherogenic diet caused dyslipidemia and led to reduction of the heart percent weight. The cytopathic effect of dyslipidemia manifested in more intense lytic injuries of cardiomyocytes, development of diffuse and small focal cardiosclerosis under conditions of manifest circulatory disorders. Remodeling of the myocardium during various periods of the experiment manifested in a higher connective tissue/cardiomyocyte volume ratio (by 74% after 30 days and by 58-62% after 64 days of experiment). Verapamil injection promoted attenuation of lytic changes in cardiomyocytes and in fibroplastic reactions of the stroma, but failed to prevent them completely.

  12. Downregulated protein expression of transcriptional activator ELK-1 in atrial myocardium of chronic AF patients.

    PubMed

    Zeng, Xiangjun; Xiao, Xuejun; Wu, Yueheng; Huang, Huanlei

    2015-01-01

    The structural alterations in atrial myocytes appear to be an adaptive response of dedifferentiation during chronic atrial fibrillation (AF). Transcriptional activator ELK-1, one of the members of ETS family, has been shown to play an important role in regulating cell differentiation, It is reasonable to presume that ELK-1 participate in the molecular and structural remodeling by which AF is sustained. To prove this hypothesis, the expression of ELK-1 protein in chronically fibrillating atria compared to that in normal rhythmic atria was detected. Right atrial myocardium were obtained from twenty-four patients undergoing valve replacement surgery, twelve patients were in chronic AF (>6 months), whereas the others were in sinus rhythm (SR). The protein expression level of ELK-1 was quantified by Western blot analysis, and the cellular localization and expression pattern of ELK-1 was examined by immunohistochemical staining and indirect immunofluorescence. Western blot analysis showed that the protein expression of ELK-1 was significantly reduced in the atrial tissue of chronic AF patients compared to that in the controls. Immunohistochemistry showed that ELK-1 immunostaining occurred in both cytosolic and nuclear compartments of atrial myocardium. Indirect immunofluorescence showed that the nuclei of normal rhythmic atrial cells were densely labeled, whereas the nuclei in chronically fibrillating atrial cells were very faintly labeled. Our results suggest that the downregulated expression of transcriptional activator ELK-1 may play an important role in the pathogenesis of AF.

  13. Discrepancy between myocardial perfusion and fatty acid metabolism following acute myocardial infarction for evaluating the dysfunctional viable myocardium.

    PubMed

    Biswas, Shankar K; Sarai, Masayoshi; Toyama, Hiroshi; Hishida, Hitoshi; Ozaki, Yukio

    2012-01-01

    Following acute myocardial infarction (AMI) the area of myocardial perfusion and metabolism mismatch is designated as dysfunctional viable myocardium. (123)I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) is clinically very useful for evaluating myocardial fatty acid metabolism, and (99)mTc-Tetrofosmin (TF) is a widely used tracer for myocardial perfusion. This study was designed to evaluate the degree of discrepancy between BMIPP and TF at the subacute state of AMI. Fifty-two patients (aged 59 ± 10 years; mean 46 years) with AMI were enrolled, and all of them underwent percutaneous coronary intervention (PCI). Patients were classified according to ST-T change and PCI timing. (123)I-beta-methyl iodophenyl pentadecanoic acid and TF cardiac scintigraphy were performed on 7 ± 3.5 days of admission using a dual headed gamma camera. Perfusion and fatty acid metabolism defect were scored on a 17 segments model. The mean BMIPP defect score on early and delayed images were 16.67 ± 10.19 and 16.25 ± 10.40, respectively. The mean TF defect score was 10 ± 7.69. Defect score of BMIPP was significantly higher than that of the TF (P < 0.0001; 95% CI 4.32-7.02), and there was a strong correlation between perfusion and metabolism defect score (r = 0.89, P < 0.00001). Forty-seven (90%) patients showed mismatched defect (BMIPP > TF), and 5 (10%) patients showed matched defect (BMIPP = TF). Mismatched defect score (MMDS) was significantly higher in patients with ST-segment elevation myocardial infarction (STEMI) than that of non-ST-segment elevation myocardial infarction (NSTEMI) (P < 0.041; 95% CI 0.11-5.19). At the subacute state of AMI, most of the patients showed perfusion-metabolism mismatch, which represents the dysfunctional viable myocardium, and patients with STEMI showed higher mismatch. Copyright © 2012 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  14. Embryonic Stem Cell Grafting in Normal and Infarcted Myocardium: Serial Assessment with MR Imaging and PET Dual Detection

    PubMed Central

    Qiao, Hui; Zhang, Hualei; Zheng, Yuanjie; Ponde, Datta E.; Shen, Dinggang; Gao, Fabao; Bakken, Ashley B.; Schmitz, Alexander; Kung, Hank F.; Ferrari, Victor A.; Zhou, Rong

    2009-01-01

    Purpose: To use magnetic resonance (MR) imaging and positron emission tomography (PET) dual detection of cardiac-grafted embryonic stem cells (ESCs) to examine (a) survival and proliferation of ESCs in normal and infarcted myocardium, (b) host macrophage versus grafted ESC contribution to serial MR imaging signal over time, and (c) cardiac function associated with the formation of grafts and whether improvement in cardiac function is related to cardiac differentiation of ESCs. Materials and Methods: All animal procedures were approved by the institutional animal care and use committee. Murine ESCs were stably transfected with a mutant version of herpes simplex virus type 1 thymidine kinase, HSV1-sr39tk, and also were labeled with superparamagnetic iron oxide (SPIO) particles. Cells were injected directly in the border zone of the infarcted heart or in corresponding regions of normal hearts in athymic rats. PET and MR imaging were performed longitudinally for 4 weeks in the same animals. Results: ESCs survived and underwent proliferation in the infarcted and normal hearts, as demonstrated by serial increases in 9-(4-[18F]fluoro-3-hydroxymethylbutyl) guanine PET signals. In parallel, the hypointense areas on MR images at the injection sites decreased over time. Double staining for host macrophages and SPIO particles revealed that the majority of SPIO-containing cells were macrophages at week 4 after injection. Left ventricular ejection fraction increased in the ESC-treated rats but decreased in culture media–treated rats, and border-zone function was preserved in ESC-treated animals; however, cardiac differentiation of ESCs was less than 0.5%. Conclusion: Dual-modality imaging permits complementary information in regard to cell survival and proliferation, graft formation, and effects on cardiac function. © RSNA, 2009 PMID:19244049

  15. Mathematically-Engineered Stromal Cell-Derived Factor 1alpha Stem Cell Cytokine Analogue Enhances Mechanical Properties of Infarcted Myocardium

    PubMed Central

    Jr, John W. MacArthur; Trubelja, Alen; Shudo, Yasuhiro; Hsiao, Philip; Fairman, Alex; Yang, Elaine; Hiesinger, William; Atluri, Pavan; Woo, Y Joseph

    2014-01-01

    Background The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilation, loss of contractile function, abnormal stress patterns and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell derived factor 1alpha analogue(ESA), improves mechanical properties of the heart post-infarction. Methods Male rats (n=54) underwent either sham surgery (n=17) with no coronary artery ligation or ligation of the LAD (n=37). Rats in the MI group were then randomized to receive either saline (0.1cc, n=18) or ESA (6μg/kg, n=19) injected into the myocardium at 4 predetermined spots around the borderzone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated utilizing custom image acquisition software, Digi-Velpo, and analyzed in MATLAB. Results Compared to the saline control group at 4 weeks, the ESA injected hearts had higher ejection fractions (71.8% ± 9.0 vs. 55.3% ± 12.6, p= 0.0004) smaller end-diastolic left ventricular internal dimensions (0.686cm ± 0.110 vs. 0.763cm ± 0.160, p= 0.04), higher cardiac output (36ml/min ± 11.6 vs. 26.9ml/min ± 7.3, p= 0.05) and the tensile modulus was lower(251kPa ± 56 vs. 301kPa ± 81, p= 0.04). The tensile modulus for the sham group was 195kPa ± 56, indicating ESA injection results in a less stiff ventricle. Conclusions Direct injection of ESA alters the biomechanical response to MI, improving the mechanical properties in the post-infarct heart. PMID:23244259

  16. Segmenting high-frequency intracardiac ultrasound images of myocardium into infarcted, ischemic, and normal regions.

    PubMed

    Hao, X; Bruce, C J; Pislaru, C; Greenleaf, J F

    2001-12-01

    Segmenting abnormal from normal myocardium using high-frequency intracardiac echocardiography (ICE) images presents new challenges for image processing. Gray-level intensity and texture features of ICE images of myocardium with the same structural/perfusion properties differ. This significant limitation conflicts with the fundamental assumption on which existing segmentation techniques are based. This paper describes a new seeded region growing method to overcome the limitations of the existing segmentation techniques. Three criteria are used for region growing control: 1) Each pixel is merged into the globally closest region in the multifeature space. 2) "Geographic similarity" is introduced to overcome the problem that myocardial tissue, despite having the same property (i.e., perfusion status), may be segmented into several different regions using existing segmentation methods. 3) "Equal opportunity competence" criterion is employed making results independent of processing order. This novel segmentation method is applied to in vivo intracardiac ultrasound images using pathology as the reference method for the ground truth. The corresponding results demonstrate that this method is reliable and effective.

  17. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Shida, Takuya; Ohori, Takashi; Suzuki, Takayuki; Matsuki, Akira; Inoue, Hiroshi

    2011-08-01

    Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

  18. Identification of Angiogenesis Rich-Viable Myocardium using RGD Dimer based SPECT after Myocardial Infarction

    PubMed Central

    Lee, Min Su; Park, Hyun Soo; Lee, Byung Chul; Jung, Jae Ho; Yoo, Jung Sun; Kim, Sang Eun

    2016-01-01

    Cardiac healing after myocardial ischemia is a complex biological process. Advances in understanding of wound healing response have paved the way for clinical testing of novel molecular imaging to improve clinical outcomes. A key factor for assessing myocardial viability after ischemic injury is the evaluation of angiogenesis accompanying increased expression of integrin αvβ3. Here, we describe the capability of an αvβ3 integrin-targeting SPECT agent, 99mTc-IDA-D-[c(RGDfK)]2, for identification of ischemic but viable myocardium, i.e., hibernating myocardium which is crucial to predict functional recovery after revascularization, the standard care of cardiovascular medicine. In vivo SPECT imaging of rat models with transient coronary occlusion showed significantly high uptake of 99mTc-IDA-D-[c(RGDfK)]2 in the ischemic region. Comparative measurements with 201Tl SPECT and 18F-FDG PET, then, proved that such prominent uptake of 99mTc-IDA-D-[c(RGDfK)]2 exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of 99mTc-IDA-D-[c(RGDfK)]2 was non-inferior to that of 18F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of 99mTc-IDA-D-[c(RGDfK)]2 corresponded to the vibrant angiogenic events with elevated expression of αvβ3 integrin. Together, these results establish that 99mTc-IDA-D-[c(RGDfK)]2 SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization. PMID:27283041

  19. Stem cells cardiac patch from decellularized umbilical artery improved heart function after myocardium infarction.

    PubMed

    Li, Na; Huang, RanRan; Zhang, XiaoXia; Xin, Yi; Li, Jia; Huang, YiMin; Cui, Wei; Stoltz, Jean-Francois; Zhou, YuJie; Kong, QingYu

    2017-01-01

    The construction of the high biocompatible biomaterials pretreated with MSC offers a promising strategy to improve the effects of stem cell therapy for the myocardial infarction (MI). However, assembling vascularized three-dimensional (3-D) myocardial tissues remains an enormous challenge. In this study, we optimized the decellularization protocol with the umbilical artery to construct microporous 3-D scaffold which is suitable for the stem cells (SC) proliferation. The SD rats underwent proximal left coronary ligation and a 5-mm diameter microporous SC patch was implanted directly on the infarct area (SC patch group). The LV contractile function, regional myocardial wall compliance, and tissue histology were assessed 4 weeks after patch implantation. The MSC patch integrated to the local heart tissue and the neo-vessels have been observed in the MSC patch. The vessels in the MSC patch were positive for the CD31 (marker for the mature endothelial cells). The left ventricle wall was thicker in the MSC patch group than the control group (p<0.05 vs. empty patch group). And the LVEF has been improved in the MSC patch group than empty patch group (59±6.7% vs. 31±4.5%, p<0.05). Our results showed that the implantation of the MSC patch improved cardiac contractile function in heart infarction rat model. The construction of artificial tissue from the decellularized umbilical artery and the MSC may open a promising perspective for the tissue therapy for MI.

  20. Effects of purified herbal extract of Salvia miltiorrhiza on ischemic rat myocardium after acute myocardial infarction.

    PubMed

    Sun, Jian; Huang, Shan Hong; Tan, Benny K-H; Whiteman, Matt; Zhu, Yi Chun; Wu, Ya Jun; Ng, Yeekong; Duan, Wei; Zhu, Yi Zhun

    2005-04-29

    In the current study, we compared purified Salvia miltiorrhiza extract (PSME) with Angiotensin-converting enzyme inhibitor, Ramipril, in in vitro experiments and also in vivo using animal model of myocardial infarction. PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals. PSME could also prevent pyrogallo red bleaching and DNA damage. After 2 weeks treatment with PSME or Ramipril, survival rates of rats with experimental myocardial infarction were marginally increased (68.2% and 71.4%) compared with saline (61.5%). The ratios of infarct size to left ventricular size in both PSME-and Ramipril-treated rats were significantly less than that in the saline-treated group. Activity of cardiac antioxidant enzyme superoxide dismutase (SOD) was significant higher while level of Thiobarbituric acid-reactive substances (TBARs) was lower in the PSME treated group. Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease.

  1. Cell therapy in reperfused acute myocardial infarction does not improve the recovery of perfusion in the infarcted myocardium: a cardiac MR imaging study.

    PubMed

    Robbers, Lourens F H J; Nijveldt, Robin; Beek, Aernout M; Hirsch, Alexander; van der Laan, Anja M; Delewi, Ronak; van der Vleuten, Pieter A; Tio, René A; Tijssen, Jan G P; Hofman, Mark B M; Piek, Jan J; Zijlstra, Felix; van Rossum, Albert C

    2014-07-01

    To investigate the effects of cell therapy on myocardial perfusion recovery after treatment of acute myocardial infarction (MI) with primary percutaneous coronary intervention (PCI). In this HEBE trial substudy, which was approved by the institutional review board (trial registry number ISRCTN95796863), the authors assessed the effects of intracoronary infusion with bone marrow-derived mononuclear cells (BMMCs) or peripheral blood-derived mononuclear cells (PBMCs) on myocardial perfusion recovery by using cardiac magnetic resonance (MR) imaging after revascularization. In 152 patients with acute MI treated with PCI, cardiac MR imaging was performed after obtaining informed consent-before randomization to BMMC, PBMC, or standard therapy (control group)-and repeated at 4-month follow-up. Cardiac MR imaging consisted of cine, rest first-pass perfusion, and late gadolinium enhancement imaging. Perfusion was evaluated semiquantitatively with signal intensity-time curves by calculating the relative upslope (percentage signal intensity change). The relative upslope was calculated for the MI core, adjacent border zone, and remote myocardium. Perfusion differences among treatment groups or between baseline and follow-up were assessed with the Wilcoxon signed rank or Mann-Whitney U test. At baseline, myocardial perfusion differed between the MI core (median, 6.0%; interquartile range [IQR], 4.1%-8.0%), border zone (median, 8.4%; IQR, 6.4%-10.2%), and remote myocardium (median, 12.2%; IQR, 10.5%-15.9%) (P < .001 for all), with equal distribution among treatment groups. These interregional differences persisted at follow-up (P < .001 for all). No difference in perfusion recovery was found between the three treatment groups for any region. After revascularization of ST-elevation MI, cell therapy does not augment the recovery of resting perfusion in either the MI core or border zone. © RSNA, 2014.

  2. Mathematically engineered stromal cell-derived factor-1α stem cell cytokine analog enhances mechanical properties of infarcted myocardium.

    PubMed

    MacArthur, John W; Trubelja, Alen; Shudo, Yasuhiro; Hsiao, Philip; Fairman, Alexander S; Yang, Elaine; Hiesinger, William; Sarver, Joseph J; Atluri, Pavan; Woo, Y Joseph

    2013-01-01

    The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction. Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB. Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle. Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  3. CXCR3-independent actions of the CXC chemokine CXCL10 in the infarcted myocardium and in isolated cardiac fibroblasts are mediated through proteoglycans

    PubMed Central

    Saxena, Amit; Bujak, Marcin; Frunza, Olga; Dobaczewski, Marcin; Gonzalez-Quesada, Carlos; Lu, Bao; Gerard, Craig; Frangogiannis, Nikolaos G.

    2014-01-01

    Aims The CXC chemokine CXCL10 is up-regulated in the infarcted myocardium and limits cardiac fibrosis by inhibiting growth factor-mediated fibroblast migration. CXCL10 signals by binding to its receptor CXCR3; however, recently CXCR3-independent CXCL10 actions have been suggested. Our study explores the role of CXCR3 signalling in myocardial infarction and investigates its involvement in mediating the anti-fibrotic effects of CXCL10. Methods and results Wild-type and CXCR3 null mice underwent reperfused infarction protocols. CXCL10 was markedly induced in the infarct; in contrast, expression of the other two CXCR3 ligands, CXCL9 and CXCL11 was extremely low. CXCR3 loss did not affect scar size, geometric ventricular remodelling, collagen deposition, and systolic dysfunction of the infarcted heart. CXCR3 null mice had increased peak neutrophil recruitment and delayed myofibroblast infiltration in the infarcted heart, but exhibited comparable myocardial expression of pro-inflammatory cytokines and chemokines. In vitro, CXCL10 did not modulate Transforming Growth Factor (TGF)-β signalling, but inhibited basic fibroblast growth factor (bFGF)-induced cardiac fibroblast migration in both wild-type and CXCR3 null cells. Treatment of fibroblasts with heparinase and chondroitinase to cleave glycosaminoglycan chains abrogated the inhibitory effects of CXCL10 on cell migration. Conclusion CXCR3 signalling does not critically regulate cardiac remodelling and dysfunction following myocardial infarction. The anti-fibrotic effects of CXCL10 in the healing infarct and in isolated cardiac fibroblasts are CXCR3-independent and may be mediated through proteoglycan signalling. Thus, administration of CXCR3-defective forms of CXCL10 may be an effective anti-fibrotic strategy in the remodelling myocardium without activating a potentially injurious, CXCR3-driven T cell response. PMID:24891401

  4. The effect of chronic digitoxin administration on the contractile state of normal and nonfailing hypertrophied myocardium.

    PubMed Central

    Williams, J F; Potter, R D

    1975-01-01

    To determine the effect of prolonged digitoxin administration on contractile function of nonfailing myocardium, right ventricular papillary muscle mechanics were examined after 6 or 24 wk of glycoside administration to control and pulmonary artery banded cats. Resting length-tension relations were not affected by digitoxin; however, isometrically developed force and the maximal rate of force development at the peak of the length-tension curve were increased in all treated groups. In untreated animals, banding resulted in a 28% incidence of deaths from heart failure. 6 wk after constriction, contractile function was depressed whereas normal function was observed 24 wk after banding. Digitoxin significantly reduced mortality from heart failure and enhanced the recovery of contractile function; contractile function in the 6 wk banded treated group approached that of untreated control and 24-wk banded groups. The long-term effects of digitoxin on contractile function were not importantly related to the temporal association between banding and institution of glycoside administration. Development of myocardial hypertrophy was comparable in treated and untreated banded groups.These results demonstrate that a significant positive inotropic effect persists in both normal and nonfailing hypertrophied myocardium during chronic digitoxin administration. PMID:124747

  5. The detection of viable myocardium by low-dose dobutamine stress speckle tracking echocardiography in patients with old myocardial infarction.

    PubMed

    Li, Liang; Wang, Fengli; Xu, Tongda; Chen, Junhong; Wang, Chaofan; Wang, Xiaoping; Li, Dongye

    2016-11-12

    To explore the significance and value of speckle-tracking echocardiography (STE) associated with low-dose dobutamine stress echocardiography (LDDSE) for the detection of viable myocardium (VM) in patients with old myocardial infarction (OMI). We performed STE with LDDSE in 33 hospitalized patients with OMI and left ventricular systolic dysfunction. QLAB software was used to analyze strain (S) and strain rate (Sr). Percutaneous coronary intervention (PCI) was subsequently performed. The movement of each wall segment was observed by routine echocardiography before and after 1, 3, and 6 months of PCI, and improvement was regarded as the gold standard for diagnosing VM. Compared with semi-quantitative wall-motion analysis combined with LDDSE, the sensitivity, specificity, and accuracy of c-STE (combining the three directions of S and Sr) at LDDSE were 91.6%, 79.5%, and 87.5%, respectively (p < 0.02). Among the deformation parameters, longitudinal strain (LS) and longitudinal strain rate (LSr) had the highest sensitivity, specificity, and accuracy. Upon combining LS and LSr at LDDSE to parallel tests, the sensitivity, specificity, and accuracy were 91.7%, 90%, and 90.6%, respectively. Compared with baseline, LVEF after PCI increased from 43.3% ± 2.6% to 47.3% ± 2.9% (p < 0.001). Global strain at LDDSE is superior to semi-quantitative wall-motion analysis with LDDSE for the assessment of VM. When the multivariable analysis and the parallel tests are combined, LS combined with LSr can be considered an independent predictor of VM. LVEF is improved after PCI in patients with VM and OMI. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:545-554, 2016. © 2016 Wiley Periodicals, Inc.

  6. Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction.

    PubMed

    Soraya, Hamid; Clanachan, Alexander S; Rameshrad, Maryam; Maleki-Dizaji, Nasrin; Ghazi-Khansari, Mahmoud; Garjani, Alireza

    2014-08-15

    Acute treatment with metformin has a protective effect in myocardial infarction by suppression of inflammatory responses due to activation of AMP-activated protein kinase (AMPK). In the present study, the effect of chronic pre-treatment with metformin on cardiac dysfunction and toll-like receptor 4 (TLR4) activities following myocardial infarction and their relation with AMPK were assessed. Male Wistar rats were randomly assigned to one of 5 groups (n=6): normal control and groups were injected isoproterenol after chronic pre-treatment with 0, 25, 50, or 100mg/kg of metformin twice daily for 14 days. Isoproterenol (100mg/kg) was injected subcutaneously on the 13th and 14th days to induce acute myocardial infarction. Isoproterenol alone decreased left ventricular systolic pressure and myocardial contractility indexed as LVdp/dtmax and LVdp/dtmin. The left ventricular dysfunction was significantly lower in the groups treated with 25 and 50mg/kg of metformin. Metfromin markedly lowered isoproterenol-induced elevation in the levels of TLR4 mRNA, myeloid differentiation protein 88 (MyD88), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) in the heart tissues. Similar changes were also seen in the serum levels of TNF-α and IL-6. However, the lower doses of 25 and 50mg/kg were more effective than 100mg/kg. Phosphorylated AMPKα (p-AMPK) in the myocardium was significantly elevated by 25mg/kg of metformin, slightly by 50mg/kg, but not by 100mg/kg. Chronic pre-treatment with metformin reduces post-myocardial infarction cardiac dysfunction and suppresses inflammatory responses, possibly through inhibition of TLR4 activities. This mechanism can be considered as a target to protect infarcted myocardium.

  7. Myocardial Infarct Size Measurement in the Mouse Chronic Infarction Model: Comparison of Area- and Length-Based Approaches

    PubMed Central

    Takagawa, Junya; Zhang, Yan; Wong, Maelene L.; Sievers, Richard E.; Kapasi, Neel K.; Wang, Yan; Yeghiazarians, Yerem; Lee, Randall J.; Grossman, William; Springer, Matthew L.

    2009-01-01

    Efficacy of potential treatments for myocardial infarction (MI) is commonly assessed by histological measurement of infarct size in rodent models. In experiments involving an acute MI setting, measurement of the infarcted area in tissue sections of the left ventricle (LV) is a standard approach to determine infarct size. This approach has also been used in the chronic infarct setting to measure infarct area several weeks post-MI. We tested the hypothesis that due to wall thinning that is known to occur in the chronic setting, the area measurement approach would be less appropriate. We compared infarct measurements in tissue sections based on (1) infarct area, (2) epicardial and endocardial infarct arc lengths, and (3) midline infarct arc length. Infarct size from all three measurement approaches correlated significantly with LV ejection fraction (LVEF) and wall motion abnormality. However, the infarct size values derived from area measurement were significantly smaller than those from the other measurements, and the range of values obtained was compressed 0.4-fold. The midline method was able to detect the expected size differences between infarcts of variable severity resulting from proximal vs. distal ligation of the coronary artery. Segmental infarct size was correlated with segmental wall motion abnormality. We conclude that both area- and length-based measurements can determine relative infarct size over a wide range of severity but the area-based measurements are substantially more compressed due to wall thinning, and that the estimation of infarct midlines is a simple, reliable approach to infarct size assessment. PMID:17347379

  8. Acute myocardial infarction associated with single vessel coronary artery disease: an analysis of clinical outcome and the prognostic importance of vessel patency and residual ischemic myocardium

    SciTech Connect

    Wilson, W.W.; Gibson, R.S.; Nygaard, T.W.; Craddock, G.B. Jr.; Watson, D.D.; Crampton, R.S.; Beller, G.A.

    1988-02-01

    The long-term outcome and the significance of residual ischemic myocardium, as assessed by predischarge exercise thallium scintigraphy and vessel patency, were studied in 97 patients with single vessel coronary artery disease by angiography 12 +/- 4 days after uncomplicated myocardial infarction. During a mean follow-up period of 39 +/- 17 months, no patients died, 6 (6%) had a recurrent nonfatal infarction and 25 (26%) experienced rapidly progressive angina requiring hospitalization. Although neither exercise-induced angina nor ST segment depression was predictive of a recurrent cardiac event, the mean number of infarct zone scan segments showing thallium redistribution (1.0 +/- 1.0 versus 0.5 +/- 0.8, p = 0.01) and the percent of patients with infarct zone redistribution (61 versus 39%, p = 0.05) were greater in those patients who experienced a late ischemic event. Kaplan-Meier analysis demonstrated a lower event-free survival rate in patients with redistribution (n = 45) than in those without redistribution (n = 52) (p = 0.019). Although no patient received immediate thrombolytic therapy, the infarct-related vessel was angiographically patent in 40 patients (41%). Vessel patency did not influence event-free survival, although a patent vessel, as compared with an occluded vessel, was associated with a greater prevalence of non-Q wave infarction (58 versus 21%, p less than 0.001), fewer persistent infarct zone thallium defects (1.2 +/- 1.1 versus 2.0 +/- 1.2, p = 0.001), more reversible infarct zone thallium defects (1.0 +/- 1.0 versus 0.5 +/- 0.9, p = 0.02) and a trend toward a higher left ventricular ejection fraction (53 +/- 10% versus 49 +/- 12%, p = 0.07).

  9. Resveratrol enhances neovascularization in the infarcted rat myocardium through the induction of thioredoxin-1, heme oxygenase-1 and vascular endothelial growth factor.

    PubMed

    Kaga, Shigeaki; Zhan, Lijun; Matsumoto, Masahiko; Maulik, Nilanjana

    2005-11-01

    We have previously shown that resveratrol possesses cardioprotective effect, which may be attributed to its ability to (i) stimulate nitric oxide production and (ii) free radical scavenging activity. Since resveratrol is one of the major components of certain varieties of red grapes, these events may underlie the cardioprotective effects thought to be obtained from moderate red wine consumption. Here we report resveratrol enhanced myocardial angiogenesis both in vivo and in vitro by induction of vascular endothelial growth factor (VEGF), which was regulated by thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO-1). Human coronary arteriolar endothelial cells exposed to resveratrol or Trx-1 on Matrigel demonstrated significantly accelerated tubular morphogenesis with induction of HO-1 and VEGF expression. This angiogenic response was repressed by tin-protoporphyrin IX (SnPP), an HO-1 inhibitor, along with downregulation of VEGF expression. However Trx-1 expression was not affected by SnPP. Again, rat neonatal cardiomyocytes treated with resveratrol significantly expressed Trx-1, HO-1 as well as VEGF. Rats were orally administered with resveratrol (1 mg/kg per day) for 14 days and then underwent permanent left anterior descending coronary artery (LAD) occlusion to document similar pro-angiogenic effect. Our results demonstrated that pretreatment with resveratrol markedly reduced infarct size 24 h after myocardial infarction (MI) and increased capillary density in the peri-infarct myocardium along with better left ventricular function 4 days after MI compared with vehicle-treated control. Concomitantly, resveratrol-treated myocardium after MI significantly induced Trx-1, HO-1 and VEGF expression. This effect was blocked by SnPP. Our findings suggest that resveratrol mediates cardioprotection and neovascularization through Trx-1-HO-1-VEGF pathway in rat ischemic myocardium.

  10. [The changes of hemodynamic parameters, pathology and c-kit mRNA expression in myocardium after acute myocardial infarction in rats].

    PubMed

    Chen, Shiqian; Long, Weifu; Wu, Wenchao; Jiang, Congxun; Liu, Xiaojing; Li, Liang

    2009-06-01

    This study was aimed to investigate the changes of hemodynamic parameters, pathology and c kit mRNA expression in myocardium after acute myocardial infarctionin (AMI) in rats, and to elucidate the relationship between these three kinds of changes. Sixty six adult male SD rats were randomly divided into normal group, Sham groups and ligation groups. The rat model of AMI was set up by ligating the left anterior descending artery. Hemodynamic parameters, pathological changes and c kit mRNA expression in myocardiam were examined. The results revealed that there were no statistically significant differences in hemodynamic parameters between normal group and Sham groups. Compared with the normal group, all ligation groups exhibited significantly decreased left ventricular systolic pressure (LVSP) and +/-dp/dtmax (P<0.01), and increased left ventricular end diastolic pressure (LVEDP, P<0.01). In the other ligation groups, compared with 6th hour group after ligation, there appeared striking increase of LVSP, LVEDP and +/-dp/dtmax (P<0.05). HE staining in myocardiam showed that there are necrosis and derangement at 24th hour group after ligation ,and a great number of inflammatory cells infiltration around the infarct zone at 3rd day group after ligation, and granulation tissue infiltrated into the infarct zone at 14th day group after ligation. In all five time points groups after ligation, the levels of c-kit mRNA expression were 0.99 fold, 1.06 fold, 1.46 fold, 1.91 fold and 2.67 fold, respectively, compared with Sham groups. The results suggest that cardiac stem cells in myocardium might contribute to the role of regenerating myocardium via self proliferation after acute myocardial infarction, but further investigation is still needed.

  11. An integrated index for automated detection of infarcted myocardium from cross-sectional echocardiograms using texton-based features (Part 1).

    PubMed

    Sudarshan, Vidya K; Acharya, U Rajendra; Ng, E Y K; Tan, Ru San; Chou, Siaw Meng; Ghista, Dhanjoo N

    2016-04-01

    Cross-sectional view echocardiography is an efficient non-invasive diagnostic tool for characterizing Myocardial Infarction (MI) and stages of expansion leading to heart failure. An automated computer-aided technique of cross-sectional echocardiography feature assessment can aid clinicians in early and more reliable detection of MI patients before subsequent catastrophic post-MI medical conditions. Therefore, this paper proposes a novel Myocardial Infarction Index (MII) to discriminate infarcted and normal myocardium using features extracted from apical cross-sectional views of echocardiograms. The cross-sectional view of normal and MI echocardiography images are represented as textons using Maximum Responses (MR8) filter banks. Fractal Dimension (FD), Higher-Order Statistics (HOS), Hu's moments, Gabor Transform features, Fuzzy Entropy (FEnt), Energy, Local binary Pattern (LBP), Renyi's Entropy (REnt), Shannon's Entropy (ShEnt), and Kapur's Entropy (KEnt) features are extracted from textons. These features are ranked using t-test and fuzzy Max-Relevancy and Min-Redundancy (mRMR) ranking methods. Then, combinations of highly ranked features are used in the formulation and development of an integrated MII. This calculated novel MII is used to accurately and quickly detect infarcted myocardium by using one numerical value. Also, the highly ranked features are subjected to classification using different classifiers for the characterization of normal and MI LV ultrasound images using a minimum number of features. Our current technique is able to characterize MI with an average accuracy of 94.37%, sensitivity of 91.25% and specificity of 97.50% with 8 apical four chambers view features extracted from only single frame per patient making this a more reliable and accurate classification.

  12. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium.

    PubMed

    Hilgendorf, Ingo; Gerhardt, Louisa M S; Tan, Timothy C; Winter, Carla; Holderried, Tobias A W; Chousterman, Benjamin G; Iwamoto, Yoshiko; Liao, Ronglih; Zirlik, Andreas; Scherer-Crosbie, Marielle; Hedrick, Catherine C; Libby, Peter; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K

    2014-05-09

    Healing after myocardial infarction involves the biphasic accumulation of inflammatory lymphocyte antigen 6C (Ly-6C)(high) and reparative Ly-6C(low) monocytes/macrophages (Mo/MΦ). According to 1 model, Mo/MΦ heterogeneity in the heart originates in the blood and involves the sequential recruitment of distinct monocyte subsets that differentiate to distinct macrophages. Alternatively, heterogeneity may arise in tissue from 1 circulating subset via local macrophage differentiation and polarization. The orphan nuclear hormone receptor, nuclear receptor subfamily 4, group a, member 1 (Nr4a1), is essential to Ly-6C(low) monocyte production but dispensable to Ly-6C(low) macrophage differentiation; dependence on Nr4a1 can thus discriminate between systemic and local origins of macrophage heterogeneity. This study tested the role of Nr4a1 in myocardial infarction in the context of the 2 Mo/MΦ accumulation scenarios. We show that Ly-6C(high) monocytes infiltrate the infarcted myocardium and, unlike Ly-6C(low) monocytes, differentiate to cardiac macrophages. In the early, inflammatory phase of acute myocardial ischemic injury, Ly-6C(high) monocytes accrue in response to a brief C-C chemokine ligand 2 burst. In the second, reparative phase, accumulated Ly-6C(high) monocytes give rise to reparative Ly-6C(low) F4/80(high) macrophages that proliferate locally. In the absence of Nr4a1, Ly-6C(high) monocytes express heightened levels of C-C chemokine receptor 2 on their surface, avidly infiltrate the myocardium, and differentiate to abnormally inflammatory macrophages, which results in defective healing and compromised heart function. Ly-6C(high) monocytes orchestrate both inflammatory and reparative phases during myocardial infarction and depend on Nr4a1 to limit their influx and inflammatory cytokine expression.

  13. Mitotically inactivated embryonic stem cells can be used as an in vivo feeder layer to nurse damaged myocardium after acute myocardial infarction: a preclinical study.

    PubMed

    Burt, Richard K; Chen, You-hong; Verda, Larissa; Lucena, Carolina; Navale, Shankararao; Johnson, Jesse; Han, Xiaoqiang; Lomasney, Jon; Baker, Jessa M; Ngai, Ka-Leung; Kino, Aya; Carr, James; Kajstura, Jan; Anversa, Piero

    2012-10-26

    Various types of viable stem cells have been reported to result in modest improvement in cardiac function after acute myocardial infarction. The mechanisms for improvement from different stem cell populations remain unknown. To determine whether irradiated (nonviable) embryonic stem cells (iESCs) improve postischemic cardiac function without adverse consequences. After coronary artery ligation-induced cardiac infarction, either conditioned media or male murine or male human iESCs were injected into the penumbra of ischemic myocardial tissue of female mice or female rhesus macaque monkeys, respectively. Murine and human iESCs, despite irradiation doses that prevented proliferation and induced cell death, significantly improved cardiac function and decreased infarct size compared with untreated or media-treated controls. Fluorescent in situ hybridization of the Y chromosome revealed disappearance of iESCs within the myocardium, whereas 5-bromo-2'-deoxyuridine assays revealed de novo in vivo cardiomyocyte DNA synthesis. Microarray gene expression profiling demonstrated an early increase in metabolism, DNA proliferation, and chromatin remodeling pathways, and a decrease in fibrosis and inflammatory gene expression compared with media-treated controls. As a result of irradiation before injection, ex vivo and in vivo iESC existence is transient, yet iESCs provide a significant improvement in cardiac function after acute myocardial infarction. The mechanism(s) of action of iESCs seems to be related to cell-cell exchange, paracrine factors, and a scaffolding effect between iESCs and neighboring host cardiomyocytes.

  14. The allometric model in chronic myocardial infarction

    PubMed Central

    2012-01-01

    Background An allometric relationship between different electrocardiogram (ECG) parameters and infarcted ventricular mass was assessed in a myocardial infarction (MI) model in New Zealand rabbits. Methods A total of fifteen animals were used, out of which ten underwent left anterior descending coronary artery ligation to induce infarction (7–35% area). Myocardial infarction (MI) evolved and stabilized during a three month-period, after which, rabbits were sacrificed and the injured area was histologically confirmed. Right before sacrifice, ECGs were obtained to correlate several of its parameters to the infarcted mass. The latter was normalized after combining data from planimetry measurements and heart weight. The following ECG parameters were studied: RR and PR intervals, P-wave duration (PD), QRS duration (QRSD) and amplitude (QRSA), Q-wave (QA), R-wave (RA) and S-wave (SA) amplitudes, T-wave peak amplitude (TA), the interval from the peak to the end of the T-wave (TPE), ST-segment deviation (STA), QT interval (QT), corrected QT and JT intervals. Corrected QT was analyzed with different correction formulae, i.e., Bazett (QTB), Framingham (QTFRA), Fridericia (QTFRI), Hodge (QTHO) and Matsunaga (QTMA) and compared thereafter. The former variables and infarcted ventricular mass were then fitted to the allometric equation in terms of deviation from normality, in turn derived after ECGs in 5 healthy rabbits. Results Six variables (JT, QTB, QA, SA, TA and STA) presented statistical differences among leads. QT showed the best allometric fit (r = 0.78), followed by TA (r = 0.77), STA (r = 0.75), QTFRA (r = 0.72), TPE (r = 0.69), QTFRI (r = 0.68) and QTMA (r = 0.68). Corrected QT’s (QTFRA, QTFRI and QTMA) performed worse than the uncorrected counterpart (QT), the former scaling allometrically with similar goodness of fits. Conclusions QT, TA, STA and TPE could possibly be used to assess infarction extent in an old MI event through the

  15. Myocardium-targeted transplantation of mesenchymal stem cells by diagnostic ultrasound-mediated microbubble destruction improves cardiac function in myocardial infarction of New Zealand rabbits.

    PubMed

    Xu, Ya-Li; Gao, Yun-Hua; Liu, Zheng; Tan, Kai-Bin; Hua, Xing; Fang, Zhen-Qiang; Wang, Ya-Li; Wang, Ya-Jie; Xia, Hong-Mei; Zhuo, Zhong-Xiong

    2010-01-21

    Therapeutic ultrasound-mediated microbubble destruction has been applied in the targeted delivery of genes, drugs and stem cells. We intended to study whether diagnostic US irradiating lipid-coated microbubble destruction combined with bone-marrow derived MSC infusion could enable the targeted delivery of MSCs into the myocardium and improve cardiac function of the myocardial infarction of New Zealand rabbits. Diagnostic ultrasound was applied to the anterior chest for 10 min after intravenous injection of lipid-coated microbubble followed by infusion of BM-MSCs. Echocardiography, histological examination, and western blotting were performed 4 weeks after cell transplantation. The cardiac function (assessed by fractional shortening and ejection fraction) was markedly improved by US+Microbubble+MSC treatment. The number of capillaries stained by HE in US+Microbubble+MSC group (47+/-23) was much greater than that of the MSCs infusion group (26+/-7), US+Microbubble group(22+/-5) and PBS infusion group (19+/-10), P<0.01. US+Microbubble stimulation induced the expression of adhesion molecule (VCAM-1) in capillaries and enhanced the myocardial permeability of microvessels. US+Microbubble-mediated supply of MSCs increased the level of VEGF in ischemic myocardium. Area of cardiac fibrosis in the US+Microbubble+MSC group was significantly decreased by 25.6%,40.1% and 46.8% when compared with MSC infusion group, US+Microbubble group and PBS infusion group, respectively. This non-invasive cell delivery system may be useful as a novel and efficient approach for angiogenic cell therapy to the infarcted myocardium. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  16. Coregistration of magnetic resonance and single photon emission computed tomography images for noninvasive localization of stem cells grafted in the infarcted rat myocardium.

    PubMed

    Shen, Dinggang; Liu, Dengfeng; Cao, Zixiong; Acton, Paul D; Zhou, Rong

    2007-01-01

    This paper demonstrates the application of mutual information based coregistration of radionuclide and magnetic resonance imaging (MRI) in an effort to use multimodality imaging for noninvasive localization of stem cells grafted in the infarcted myocardium in rats. Radionuclide imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) inherently has high sensitivity and is suitable for tracking of labeled stem cells, while high-resolution MRI is able to provide detailed anatomical and functional information of myocardium. Thus, coregistration of PET or SPECT images with MRI will map the location and distribution of stem cells on detailed myocardium structures. To validate this coregistration method, SPECT data were simulated by using a Monte Carlo-based projector that modeled the pinhole-imaging physics assuming nonzero diameter and photon penetration at the edge. Translational and rotational errors of the coregistration were examined with respect to various SPECT activities, and they are on average about 0.50 mm and 0.82 degrees , respectively. Only the rotational error is dependent on activity of SPECT data. Stem cells were labeled with (111)Indium oxyquinoline and grafted in the ischemic myocardium of a rat model. Dual-tracer small-animal SPECT images were acquired, which allowed simultaneous detection of (111)In-labeled stem cells and of [(99m)Tc]sestamibi to assess myocardial perfusion deficit. The same animals were subjected to cardiac MRI. A mutual-information-based coregistration method was then applied to the SPECT and MRIs. By coregistration, the (111)In signal from labeled cells was mapped into the akinetic region identified on cine MRIs; the regional perfusion deficit on the SPECT images also coincided with the akinetic region on the MR image.

  17. [The role of multispiral computed tomography in assessment of viability of the myocardium and prognostication of left ventricular remodeling in patients with ST-elevation myocardial infarction].

    PubMed

    Veselova, T N; Merkulova, I N; Iarovaia, E B; Ternovoĭ, S K; Ruda, M Ia

    2013-01-01

    Aim of the study was to assess perfusion defect and viability of the myocardium by the method of multispiral computed tomography (MSCT) in patients with ST-elevation acute myocardial infarction (AMI) and to assess their prognostic role in development of remodeling of the left ventricle (LV). We included into the study 117 patients with AMI. MSCT with intravenous contrast enhancement was carried out on days 3-4 and at 12 months after AMI. In the arterial phase we estimated volume of myocardial perfusion defect, LV end diastolic and end systolic volumes (LVEDV and LVESV), and LV ejection fraction (EF). Three types of myocardial opacification were distinguished on tomograms in delayed phase of MSCT: type I - subendocardial residual defect (RD), type II - transmural RD, type III - transmural delayed hyper enhancement (DE). Patients were divided in 3 groups: (1) with subendocardial RD (n=63), (2) with transmural RD (n=28), (3) with transmural DE (n=26). Development of LV remodeling was registered if at repeat MSCT LVEDV increased more or equal 20% from baseline. In patients with signs of viable myocardium (group 1) volume of perfusion defect was substantially smaller than in patients with nonviable myocardium (groups 2 and 3): 1cm3 (0.4-2.4) vs. 7.3 cm3 (5.3-10.0) and 6.3 cm3 (5.0-15.0), respectively, p<0.001. Compared with groups 2 and 3 patients of group 1 more often were female (p=0.04), had inferior MI (p<0.001), and spontaneous reperfusion (p<0.001). After 12 months LV remodeling was registered in 19.3% of patients, all had signs of nonviable myocardium in more or equal 3 LV segments. In patients with perfusion defect more or equal 10 cm3 probability of development of LV remodeling exceeded 50%. Disturbances of perfusion abnormalities and number of nonviable LV segments were main predictors of LV remodeling.

  18. Embolization of the first diagonal branch of the left anterior descending coronary artery as a porcine model of chronic trans-mural myocardial infarction.

    PubMed

    Hanes, Derek W; Wong, Maelene L; Jenny Chang, C W; Humphrey, Sterling; Grayson, J Kevin; Boyd, Walter D; Griffiths, Leigh G

    2015-06-06

    significantly greater in the infarcted region than in normal myocardium (p = 0.007 and p = 0.018, respectively); however, pyridinoline crosslink content per collagen I content in the infarcted region was significantly less than normal myocardium (p = 0.048). Systolic dysfunction and changes in ECM composition induced via embolization of the D1-LAD closely mimic those found in individuals with chronic myocardial infarction (MI), and represents a location visible without the need for anesthesia. As a result, this method represents a useful model for studying chronic MI.

  19. Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression.

    PubMed

    Sirry, Mazin S; Butler, J Ryan; Patnaik, Sourav S; Brazile, Bryn; Bertucci, Robbin; Claude, Andrew; McLaughlin, Ron; Davies, Neil H; Liao, Jun; Franz, Thomas

    2016-10-01

    Understanding the passive mechanical properties of infarcted tissue at different healing stages is essential to explore the emerging biomaterial injection-based therapy for myocardial infarction (MI). Although rats have been widely used as animal models in such investigations, the data in literature that quantify the passive mechanical properties of rat heart infarcts is very limited. MI was induced in rats and hearts were harvested immediately (0 day), 7, 14 and 28 days after infarction onset. Left ventricle anterioapical samples were cut and underwent equibiaxial and non equibiaxial tension followed by uniaxial compression mechanical tests. Histological analysis was conducted to confirm MI and to quantify the size of the induced infarcts. Infarcts maintained anisotropy and the nonlinear biaxial and compressive mechanical behaviour throughout the healing phases with the circumferential direction being stiffer than the longitudinal direction. Mechanical coupling was observed between the two axes in all infarct groups. The 0, 7, 14 and 28 days infarcts showed 438, 693, 1048 and 1218kPa circumferential tensile moduli. The 28 day infarct group showed a significantly higher compressive modulus compared to the other infarct groups (p=0.0060, 0.0293, and 0.0268 for 0, 7 and 14 days groups). Collagen fibres were found to align in a preferred direction for all infarct groups supporting the observed mechanical anisotropy. The presented data are useful for developing material models for healing infarcts and for setting a baseline for future assessment of emerging mechanical-based MI therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. An integrated inverse model-experimental approach to determine soft tissue three-dimensional constitutive parameters: application to post-infarcted myocardium.

    PubMed

    Avazmohammadi, Reza; Li, David S; Leahy, Thomas; Shih, Elizabeth; Soares, João S; Gorman, Joseph H; Gorman, Robert C; Sacks, Michael S

    2017-08-31

    Knowledge of the complete three-dimensional (3D) mechanical behavior of soft tissues is essential in understanding their pathophysiology and in developing novel therapies. Despite significant progress made in experimentation and modeling, a complete approach for the full characterization of soft tissue 3D behavior remains elusive. A major challenge is the complex architecture of soft tissues, such as myocardium, which endows them with strongly anisotropic and heterogeneous mechanical properties. Available experimental approaches for quantifying the 3D mechanical behavior of myocardium are limited to preselected planar biaxial and 3D cuboidal shear tests. These approaches fall short in pursuing a model-driven approach that operates over the full kinematic space. To address these limitations, we took the following approach. First, based on a kinematical analysis and using a given strain energy density function (SEDF), we obtained an optimal set of displacement paths based on the full 3D deformation gradient tensor. We then applied this optimal set to obtain novel experimental data from a 1-cm cube of post-infarcted left ventricular myocardium. Next, we developed an inverse finite element (FE) simulation of the experimental configuration embedded in a parameter optimization scheme for estimation of the SEDF parameters. Notable features of this approach include: (i) enhanced determinability and predictive capability of the estimated parameters following an optimal design of experiments, (ii) accurate simulation of the experimental setup and transmural variation of local fiber directions in the FE environment, and (iii) application of all displacement paths to a single specimen to minimize testing time so that tissue viability could be maintained. Our results indicated that, in contrast to the common approach of conducting preselected tests and choosing an SEDF a posteriori, the optimal design of experiments, integrated with a chosen SEDF and full 3D kinematics, leads

  1. Mesenchymal stem cell delivery into rat infarcted myocardium using a porous polysaccharide-based scaffold: a quantitative comparison with endocardial injection

    PubMed Central

    Le Visage, Catherine; Gournay, Olivier; Benguirat, Najah; Hamidi, Sofiane; Chaussumier, Laetitia; Mougenot, Nathalie; Flanders, James A.; Isnard, Richard; Michel, Jean-Baptiste; Hatem, Stéphane N.; Letourneur, Didier; Norol, Francoise

    2012-01-01

    The use of mesenchymal stem cells (MSCs) for tissue regeneration is often hampered by modest engraftment in host tissue. This study was designed to quantitatively compare MSCs engraftment rates after delivery using a polysaccharide-based porous scaffold or endocardial (EC) injection in a rat myocardial infarction model. Cellular engraftment was measured by quantitative RT-PCR using MSCs previously transduced with a lentiviral vector that expresses GFP. The use of a scaffold promoted local cellular engraftment and survival. The number of residual GFP+ cells was greater with the scaffold than after EC injection (9.7% vs 5.1% at 1 month and 16.3% vs 6.1% at 2 months, respectively (n=5)). This concurred with a slight increase in mRNA VEGF level in the scaffold group (p<0.05). Clusters of GFP+ cells were detected in the peri-infarct area, mainly phenotypically consistent with immature MSCs. Functional assessment by echocardiography at 2 months post infarct also showed a trend towards a lower left ventricular dilatation and a reduced fibrosis in the scaffold group in comparison to direct injection group (n=10). These findings demonstrate that using a porous biodegradable scaffold is a promising method to improve cell delivery and engraftment into damaged myocardium. PMID:21770864

  2. Implantation of a Poly-L-Lactide GCSF-Functionalized Scaffold in a Model of Chronic Myocardial Infarction.

    PubMed

    Spadaccio, Cristiano; Nappi, Francesco; De Marco, Federico; Sedati, Pietro; Taffon, Chiara; Nenna, Antonio; Crescenzi, Anna; Chello, Massimo; Trombetta, Marcella; Gambardella, Ivancarmine; Rainer, Alberto

    2017-02-01

    A previously developed poly-L-lactide scaffold releasing granulocyte colony-stimulating factor (PLLA/GCSF) was tested in a rabbit chronic model of myocardial infarction (MI) as a ventricular patch. Control groups were constituted by healthy, chronic MI and nonfunctionalized PLLA scaffold. PLLA-based electrospun scaffold efficiently integrated into a chronic infarcted myocardium. Functionalization of the biopolymer with GCSF led to increased fibroblast-like vimentin-positive cellular colonization and reduced inflammatory cell infiltration within the micrometric fiber mesh in comparison to nonfunctionalized scaffold; PLLA/GCSF polymer induced an angiogenetic process with a statistically significant increase in the number of neovessels compared to the nonfunctionalized scaffold; PLLA/GCSF implanted at the infarcted zone induced a reorganization of the ECM architecture leading to connective tissue deposition and scar remodeling. These findings were coupled with a reduction in end-systolic and end-diastolic volumes, indicating a preventive effect of the scaffold on ventricular dilation, and an improvement in cardiac performance.

  3. Single-Dose Gadobutrol in Comparison With Single-Dose Gadobenate Dimeglumine for Magnetic Resonance Imaging of Chronic Myocardial Infarction at 3 T

    PubMed Central

    Wildgruber, Moritz; Stadlbauer, Thomas; Rasper, Michael; Hapfelmeier, Alexander; Zelger, Otto; Eckstein, Hans-Henning; Halle, Martin; Rummeny, Ernst J.; Huber, Armin M.

    2014-01-01

    Objectives The aim of this study was to compare the contrast-to-noise ratio (CNR) values of infarct and remote myocardium as well as infarct and blood after application of 0.1 mmol/kg gadobutrol and 0.1 mmol/kg gadobenate dimeglumine on late gadolinium enhancement magnetic resonance (MR) images. Material and Methods The study was a prospective randomized controlled clinical study. After informed consent was obtained, 20 patients (12 men, 8 women; mean age, 67 ± 11 years) with known chronic myocardial infarction were included for an intraindividual comparison of a single-dose gadobutrol and a single-dose gadobenate dimeglumine. Two MR imaging examinations were performed within a period of 28 days in a crossover design. Late gadolinium enhancement imaging was performed 10 minutes after gadolinium administration using a 2-dimensional phase-sensitive inversion recovery gradient echo sequence at 3 T. Infarct size, signal intensities (SIs), signal-to-noise ratio, and CNR were determined on phase-sensitive MR images. Values for CNR were calculated as CNRinfarct/myocardium = (SIinfarct − SImyocardium)/SDnoise and CNRinfarct/blood = (SIinfarct − SIblood)/SDnoise. In addition, the areas of myocardial infarction were determined on single slices. The entire infarct volumes were calculated by adding the areas with hyperenhancement multiplied by the slice thickness. Results Late gadolinium enhancement was present in all patients. Median values of the infarct area, infarct volume, and transmurality for gadobutrol and gadobenate dimeglumine showed good to excellent concordance (rc = 0.85, rc = 0.95, and rc = 0.71, respectively). The mean signal-to-noise ratio values for infarct, remote myocardium, and ventricular blood were 18.6 ± 6.5, 4.1 ± 3.7, and 14.6 ± 7.5, respectively, for gadobutrol and 18.8 ± 8.9, 4.9 ± 4.5, and 17.8 ± 10.1, respectively, for gadobenate dimeglumine (P = 0.93, P = 0.48, and P = 0.149, respectively). The mean values of CNRinfarct/myocardium and

  4. Myocardial Infarction Triggers Chronic Cardiac Autoimmunity in Type 1 Diabetes

    PubMed Central

    Gottumukkala, Raju V.; Lv, HuiJuan; Cornivelli, Lizbeth; Wagers, Amy J.; Kwong, Raymond Y.; Bronson, Roderick; Stewart, Garrick C.; Schulze, P. Christian; Chutkow, William; Wolpert, Howard A.; Lee, Richard T.; Lipes, Myra A.

    2015-01-01

    Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality following myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert ‘adjuvant effects’ and induce pathological responses in autoimmune-prone T1D hosts. Here we show that experimental MI in nonobese diabetic (NOD) mice - but not in control C57BL/6 mice - results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac IgG autoantibody production and Th1 effector cell responses against cardiac (α-)myosin. PIA was prevented by inducing tolerance to α-myosin, demonstrating that immune responses to cardiac myosin are required for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and non-diabetic patients with myocarditis – that were absent in post-MI type 2 diabetic patients - and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D, and highlight a role for antigen-specific immunointervention to selectively block this pathway. PMID:22700956

  5. The feasibility of the initial postsystolic to systolic strain rate ratio as a predictor of the viability of ischemic myocardium with acute myocardial infarction.

    PubMed

    Park, Soon Chang; Kang, Ki-Woon; Yoon, Hyeon Soo; Myung, Jin Cheol; Choi, Yu Jeong; Park, Sang Hyun; Jung, Kyung Tae; Chin, Jung Yeon

    2014-08-01

    Investigations of a strain index for the viability of ischemic myocardium with acute myocardial infarction (AMI) have been challenging. Therefore, the aim of this study was to evaluate patients with AMI to determine an optimal strain index for predicting the viability of ischemic myocardium. A total of 57 patients with AMI were assessed according to two-dimensional (2D) speckle tracking imaging strain and strain rate (SR), measured during the acute phase before urgent revascularization and at a 1-year follow-up postrevascularization. During the acute phase, all the myocardial segments were classified according to the acute end-systolic strain (Ses) values as normal (Ses ≤ -13%), hypocontractile (-13% < Ses ≤ -7%), or having a severe contractile abnormality (Ses > -7%). At the 1-year follow-up, we reassessed the recovery of the segments with a severe contractile abnormality. The viability of these segments was defined as an improved Ses (≤ -7%) at follow-up postrevascularization. The Ses values, postsystolic strain index (PSI), and SR values were significantly better in the viable segments than in the nonviable segments at both the acute phase and at follow-up (P < 0.001). The initial postsystolic to systolic SR ratio (SRps/SRs) had the best area under the curve (AUC = 0.897). In addition, a cutoff value of 0.6 predicted recovery from a severe contractile abnormality with a sensitivity of 75% and a specificity of 88%. The initial SRps/SRs ratio identified the viability of ischemic myocardium with AMI; therefore, this novel index may be clinically useful in the treatment of patients with AMI. © 2013, Wiley Periodicals, Inc.

  6. Determination of location, size, and transmurality of chronic myocardial infarction without exogenous contrast media by using cardiac magnetic resonance imaging at 3 T.

    PubMed

    Kali, Avinash; Cokic, Ivan; Tang, Richard L Q; Yang, Hsin-Jung; Sharif, Behzad; Marbán, Eduardo; Li, Debiao; Berman, Daniel S; Dharmakumar, Rohan

    2014-05-01

    Late-gadolinium-enhanced (LGE) cardiac MRI (CMR) is a powerful method for characterizing myocardial infarction (MI), but the requisite gadolinium infusion is estimated to be contraindicated in ≈20% of patients with MI because of end-stage chronic kidney disease. The purpose of this study is to investigate whether T1 CMR obtained without contrast agents at 3 T could be an alternative to LGE CMR for characterizing chronic MIs using a canine model of MI. Canines (n=29) underwent CMR at 7 days (acute MI [AMI]) and 4 months (chronic MI [CMI]) after MI. Infarct location, size, and transmurality measured by using native T1 maps and LGE images at 1.5 T and 3 T were compared. Resolution of edema between AMI and CMI was examined with T2 maps. T1 maps overestimated infarct size and transmurality relative to LGE images in AMI (P=0.016 and P=0.007, respectively), which was not observed in CMI (P=0.49 and P=0.81, respectively) at 3 T. T1 maps underestimated infarct size and transmurality relative to LGE images in AMI and CMI (P<0.001) at 1.5 T. Relative to the remote territories, T1 of the infarcted myocardium was increased in CMI and AMI (P<0.05), and T2 of the infarcted myocardium was increased in AMI (P<0.001) but not in CMI (P>0.20) at both field strengths. Histology showed extensive replacement fibrosis within the CMI territories. CMI detection sensitivity and specificity of T1 CMR at 3 T were 95% and 97%, respectively. Native T1 maps at 3 T can determine the location, size, and transmurality of CMI with high diagnostic accuracy. Patient studies are necessary for clinical translation. © 2014 American Heart Association, Inc.

  7. Determination of Location, Size and Transmurality of Chronic Myocardial Infarction Without Exogenous Contrast Media Using Cardiac Magnetic Resonance Imaging at 3T

    PubMed Central

    Kali, Avinash; Cokic, Ivan; Tang, Richard L Q; Yang, Hsin-Jung; Sharif, Behzad; Marbán, Eduardo; Li, Debiao; Berman, Daniel; Dharmakumar, Rohan

    2014-01-01

    Background LGE CMR is a powerful method for characterizing MI, but the requisite gadolinium infusion is estimated to be contraindicated in nearly 20% of MI patients due to end-stage chronic kidney disease. The purpose of this study is to investigate whether T1 Cardiovascular-Magnetic-Resonance Imaging (CMR) obtained without contrast agents at 3T could be an alternative to Late-Gadolinium-Enhanced (LGE) CMR for characterizing chronic myocardial infarctions (MIs) using a canine model of MI. Methods and Results Canines (n=29) underwent CMR at 7 days (acute, AMI) and 4 months (chronic, CMI) post-MI. Infarct location, size and transmurality measured using native T1 maps and LGE images at 1.5T and 3T were compared. Resolution of edema between AMI and CMI was examined with T2 maps. T1 maps overestimated infarct size and transmurality relative to LGE images in AMI (p=0.016 and p=0.007, respectively), which was not observed in CMI (p=0.49 and p=0.81, respectively), at 3T. T1 maps underestimated infarct size and transmurality relative to LGE images in AMI and CMI (p<0.001), at 1.5T. Relative to the remote territories, T1 of the infarcted myocardium was increased in CMI and AMI (p<0.05); and T2 of the infarcted myocardium was increased in AMI (p<0.001), but not in CMI (p >0.20) at both field strengths. Histology showed extensive replacement fibrosis within the CMI territories. CMI detection sensitivity and specificity of T1 CMR at 3T were 95% and 97%, respectively. Conclusions Native T1 maps at 3T can determine the location, size and transmurality of CMI with high diagnostic accuracy. Patient studies are necessary for clinical translation. PMID:24682268

  8. Huoxue Anxin Recipe () promotes myocardium angiogenesis of acute myocardial infarction rats by up-regulating miR-210 and vascular endothelial growth factor.

    PubMed

    Wang, Jie; Zhang, Yun; Liu, Yong-Mei; Guo, Li-Li; Wu, Ping; Dong, Yu; Wu, Guang-Jun

    2016-09-01

    To investigate the microRNAs (miRNAs) expression profile of acute myocardial infarction (AMI) rats and the regulating effects of Huoxue Anxin Recipe (, HAR) on angiogenesis-related miRNAs and genes. Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups (15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miRNAs expression profile was detected by quantitative realtime polymerase chain reaction (qRT-PCR). The mRNA and protein expressions of vascular endothelial growth factor (VEGF), and a target gene of miR-210 was further detected by qRT-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. Compared with the sham group, ejection fraction (EF) and fractional shortening (FS) values were decreased significantly in the AMI group (P<0.01), while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly (P<0.05 vs. AMI group), and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miRNAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miRNAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mRNA and protein expressions of VEGF were decreased significantly in the AMI group (P<0.05 vs. sham

  9. Thyroid hormone improves the mechanical performance of the post-infarcted diabetic myocardium: a response associated with up-regulation of Akt/mTOR and AMPK activation.

    PubMed

    Mourouzis, Iordanis; Giagourta, Irini; Galanopoulos, Georgios; Mantzouratou, Polixeni; Kostakou, Erietta; Kokkinos, Alexandros D; Tentolouris, Nikolaos; Pantos, Constantinos

    2013-10-01

    Thyroid hormone (TH) is shown to be protective against cardiac and pancreatic injury. Thus, this study explored the potential effects of TH treatment on the functional status of the postinfarcted diabetic myocardium. Diabetic patients have worse prognosis after acute myocardial infarction (AMI). AMI was induced by left coronary ligation in rats previously treated with 35 mg/kg streptozotocin (STZ), (DM-AMI). TH treatment was initiated at 2 weeks after AMI and continued for 6 weeks (DM-AMI+TH), while sham-operated animals served as control (DM-SHAM). TH treatment increased cardiac mass, improved wall stress and favorably changed cardiac geometry. TH significantly increased echocardiographic left ventricular ejection fraction (LVEF%): [54.2 (6.5) for DM-AMI+TH vs 37 (2.0) for DM-AMI, p<0.05]. TH treatment resulted in significantly increased insulin and decreased glucose levels in serum. The ratios of phosphorylated (p)-Akt/total Akt and p-mTOR/total mTOR were increased 2.0 fold and 2.7 fold in DM-AMI+TH vs DM-AMI respectively, p<0.05. Furthermore, the ratio of p-AMPK/total AMPK was found to be increased 1.6 fold in DM-AMI+TH vs DM-AMI, p<0.05. TH treatment improved the mechanical performance of the post-infarcted myocardium in rats with STZ-induced diabetes, an effect which was associated with Akt/mTOR and AMPK activation. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Impact of low signal intensity assessed by cine magnetic resonance imaging on detection of poorly viable myocardium in patients with prior myocardial infarction.

    PubMed

    Ota, Shingo; Tanimoto, Takashi; Orii, Makoto; Hirata, Kumiko; Shiono, Yasutsugu; Shimamura, Kunihiro; Matsuo, Yoshiki; Yamano, Takashi; Ino, Yasushi; Kitabata, Hironori; Yamaguchi, Tomoyuki; Kubo, Takashi; Tanaka, Atsushi; Imanishi, Toshio; Akasaka, Takashi

    2015-05-13

    Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) has been established as a modality to detect myocardial infarction (MI). However, the use of gadolinium contrast is limited in patients with advanced renal dysfunction. Although the signal intensity (SI) of infarct area assessed by cine MRI is low in some patients with prior MI, the prevalence and clinical significance of low SI has not been evaluated. The aim of this study was to evaluate how low SI assessed by cine MRI may relate to the myocardial viability in patients with prior MI. Fifty patients with prior MI underwent both cine MRI and LGE-MRI. The left ventricle was divided into 17 segments. The presence of low SI and the wall motion score (WMS) of each segment were assessed by cine MRI. The transmural extent of infarction was evaluated by LGE-MRI. LGE was detected in 329 of all 850 segments (39%). The low SI assessed by cine MRI was detected in 105 of 329 segments with LGE (32%). All segments with low SI had LGE. Of all 329 segments with LGE, the segments with low SI showed greater transmural extent of infarction (78 [72 - 84] % versus 53 [38 - 72] %, P < 0.01), thinner wall (4.0[3.1 - 4.8] mm versus 6.5 [5.2 - 8.1] mm, P < 0.01), and higher WMS (4.0 [4.0 - 4.0] versus 2.0 [2.0 - 3.0], P < 0.01). The low SI assessed by cine MRI may be effective for detecting poorly viable myocardium in patients with prior MI.

  11. Viscoelastic properties of normal and infarcted myocardium measured by a multifrequency shear wave method: comparison with pressure-segment length method.

    PubMed

    Pislaru, Cristina; Urban, Matthew W; Pislaru, Sorin V; Kinnick, Randall R; Greenleaf, James F

    2014-08-01

    Our aims were (i) to compare in vivo measurements of myocardial elasticity by shear wave dispersion ultrasound vibrometry (SDUV) with those by the conventional pressure-segment length method, and (ii) to quantify changes in myocardial viscoelasticity during systole and diastole after reperfused acute myocardial infarction. The shear elastic modulus (μ1) and viscous coefficient (μ2) of left ventricular myocardium were measured by SDUV in 10 pigs. Young's elastic modulus was independently measured by the pressure-segment length method. Measurements made with the SDUV and pressure-segment length methods were strongly correlated. At reperfusion, μ1 and μ2 in end-diastole were increased. Less consistent changes were found during systole. In all animals, μ1 increased linearly with left ventricular pressure developed during systole. Preliminary results suggest that μ1 is preload dependent. This is the first study to validate in vivo measurements of myocardial elasticity by a shear wave method. In this animal model, the alterations in myocardial viscoelasticity after a myocardial infarction were most consistently detected during diastole. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  12. Cardiovascular magnetic resonance of the myocardium at risk in acute reperfused myocardial infarction: comparison of T2-weighted imaging versus the circumferential endocardial extent of late gadolinium enhancement with transmural projection.

    PubMed

    Ubachs, Joey F A; Engblom, Henrik; Erlinge, David; Jovinge, Stefan; Hedström, Erik; Carlsson, Marcus; Arheden, Håkan

    2010-03-29

    In the situation of acute coronary occlusion, the myocardium supplied by the occluded vessel is subject to ischemia and is referred to as the myocardium at risk (MaR). Single photon emission computed tomography has previously been used for quantitative assessment of the MaR. It is, however, associated with considerable logistic challenges for employment in clinical routine. Recently, T2-weighted cardiovascular magnetic resonance (CMR) has been introduced as a new method for assessing MaR several days after the acute event. Furthermore, it has been suggested that the endocardial extent of infarction as assessed by late gadolinium enhanced (LGE) CMR can also be used to quantify the MaR. Hence, we sought to assess the ability of endocardial extent of infarction by LGE CMR to predict MaR as compared to T2-weighted imaging. Thirty-seven patients with early reperfused first-time ST-segment elevation myocardial infarction underwent CMR imaging within the first week after percutaneous coronary intervention. The ability of endocardial extent of infarction by LGE CMR to assess MaR was evaluated using T2-weighted imaging as the reference method. MaR determined with T2-weighted imaging (34 +/- 10%) was significantly higher (p < 0.001) compared to the MaR determined with endocardial extent of infarction (23 +/- 12%). There was a weak correlation between the two methods (r2 = 0.17, p = 0.002) with a bias of -11 +/- 12%. Myocardial salvage determined with T2-weighted imaging (58 +/- 22%) was significantly higher (p < 0.001) compared to myocardial salvage determined with endocardial extent of infarction (45 +/- 23%). No MaR could be determined by endocardial extent of infarction in two patients with aborted myocardial infarction. This study demonstrated that the endocardial extent of infarction as assessed by LGE CMR underestimates MaR in comparison to T2-weighted imaging, especially in patients with early reperfusion and aborted myocardial infarction.

  13. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium.

    PubMed

    Witayavanitkul, Namthip; Ait Mou, Younss; Kuster, Diederik W D; Khairallah, Ramzi J; Sarkey, Jason; Govindan, Suresh; Chen, Xin; Ge, Ying; Rajan, Sudarsan; Wieczorek, David F; Irving, Thomas; Westfall, Margaret V; de Tombe, Pieter P; Sadayappan, Sakthivel

    2014-03-28

    Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, is proteolyzed post-MI in humans, which results in an N-terminal fragment, C0-C1f. The presence of C0-C1f in cultured cardiomyocytes results in decreased Ca(2+) transients and cell shortening, abnormalities sufficient for the induction of heart failure in a mouse model. However, the underlying mechanisms remain unclear. Here, we investigate the association between C0-C1f and altered contractility in human cardiac myofilaments in vitro. To accomplish this, we generated recombinant human C0-C1f (hC0C1f) and incorporated it into permeabilized human left ventricular myocardium. Mechanical properties were studied at short (2 μm) and long (2.3 μm) sarcomere length (SL). Our data demonstrate that the presence of hC0C1f in the sarcomere had the greatest effect at short, but not long, SL, decreasing maximal force and myofilament Ca(2+) sensitivity. Moreover, hC0C1f led to increased cooperative activation, cross-bridge cycling kinetics, and tension cost, with greater effects at short SL. We further established that the effects of hC0C1f occur through direct interaction with actin and α-tropomyosin. Our data demonstrate that the presence of hC0C1f in the sarcomere is sufficient to induce depressed myofilament function and Ca(2+) sensitivity in otherwise healthy human donor myocardium. Decreased cardiac function post-MI may result, in part, from the ability of hC0C1f to bind actin and α-tropomyosin, suggesting that cleaved C0-C1f could act as a poison polypeptide and disrupt the interaction of native cardiac myosin-binding protein C with the thin filament.

  14. Noninvasive electrocardiographic imaging of chronic myocardial infarct scar.

    PubMed

    Horáček, B Milan; Wang, Linwei; Dawoud, Fady; Xu, Jingjia; Sapp, John L

    2015-01-01

    Myocardial infarction (MI) scar constitutes a substrate for ventricular tachycardia (VT), and an accurate delineation of infarct scar may help to identify reentrant circuits and thus facilitate catheter ablation. One of the recent advancements in characterization of a VT substrate is its volumetric delineation within the ventricular wall by noninvasive electrocardiographic imaging. This paper compares, in four specific cases, epicardial and volumetric inverse solutions, using magnetic resonance imaging (MRI) with late gadolinium enhancement as a gold standard. For patients with chronic MI, who presented at Glasgow Western Infirmary, delayed-enhancement MRI and 120-lead body surface potential mapping (BSPM) data were acquired and 4 selected cases were later made available to a wider community as part of the 2007 PhysioNet/Computers in Cardiology Challenge. These data were used to perform patient-specific inverse solutions for epicardial electrograms and morphology-based criteria were applied to delineate infarct scar on the epicardial surface. Later, the Rochester group analyzed the same data by means of a novel inverse solution for reconstructing intramural transmembrane potentials, to delineate infarct scar in three dimensions. Comparison of the performance of three specific inverse-solution algorithms is presented here, using scores based on the 17-segment ventricular division scheme recommended by the American Heart Association. The noninvasive methods delineating infarct scar as three-dimensional (3D) intramural distribution of transmembrane action potentials outperform estimates providing scar delineation on the epicardial surface in all scores used for comparison. In particular, the extent of infarct scar (its percentage mass relative to the total ventricular mass) is rendered more accurately by the 3D estimate. Moreover, the volumetric rendition of scar border provides better clues to potential targets for catheter ablation. Electrocardiographic inverse

  15. Noninvasive electrocardiographic imaging of chronic myocardial infarct scar§

    PubMed Central

    Horáček, B. Milan; Wang, Linwei; Dawoud, Fady; Xu, Jingjia; Sapp, John L.

    2015-01-01

    Background Myocardial infarction (MI) scar constitutes a substrate for ventricular tachycardia (VT), and an accurate delineation of infarct scar may help to identify reentrant circuits and thus facilitate catheter ablation. One of the recent advancements in characterization of a VT substrate is its volumetric delineation within the ventricular wall by noninvasive electrocardiographic imaging. This paper compares, in four specific cases, epicardial and volumetric inverse solutions, using magnetic resonance imaging (MRI) with late gadolinium enhancement as a gold standard. Methods For patients with chronic MI, who presented at Glasgow Western Infirmary, delayed-enhancement MRI and 120-lead body surface potential mapping (BSPM) data were acquired and 4 selected cases were later made available to a wider community as part of the 2007 PhysioNet/Computers in Cardiology Challenge. These data were used to perform patient-specific inverse solutions for epicardial electrograms and morphology-based criteria were applied to delineate infarct scar on the epicardial surface. Later, the Rochester group analyzed the same data by means of a novel inverse solution for reconstructing intramural transmembrane potentials, to delineate infarct scar in three dimensions. Comparison of the performance of three specific inverse-solution algorithms is presented here, using scores based on the 17-segment ventricular division scheme recommended by the American Heart Association. Results The noninvasive methods delineating infarct scar as three-dimensional (3D) intramural distribution of transmembrane action potentials outperform estimates providing scar delineation on the epicardial surface in all scores used for comparison. In particular, the extent of infarct scar (its percentage mass relative to the total ventricular mass) is rendered more accurately by the 3D estimate. Moreover, the volumetric rendition of scar border provides better clues to potential targets for catheter ablation

  16. Intramyocardial delivery of basic fibroblast growth factor-impregnated gelatin hydrogel microspheres enhances collateral circulation to infarcted canine myocardium.

    PubMed

    Yamamoto, T; Suto, N; Okubo, T; Mikuniya, A; Hanada, H; Yagihashi, S; Fujita, M; Okumura, K

    2001-05-01

    The present study examined whether basic fibroblast growth factor (bFGF)-impregnated acidic gelatin hydrogel microspheres (AGHM) would enhance collateral development to the infarct area in dogs with coronary occlusion. Studies were conducted in 28 dogs with a 2-week occlusion of the proximal left anterior descending coronary artery (LAD). The dogs were divided into 3 groups according to treatment: Group A treated with bFGF-impregnated AGHM in the infarct area; Group B with free-form bFGF; Group C with AGHM alone. Coronary angiography (n=15; Group A, 7 dogs; Group B, 5 dogs; Group C, 3 dogs) and a regional myocardial blood flow study (n=13; Group A, 6 dogs; Group B, 4 dogs; Group C, 3 dogs) were repeated at a 2-week interval. Coronary angiography revealed that in Group A, antegrade flow in the LAD distal to the occlusion, which was assessed by Thrombolysis in Myocardial Infarction (TIMI) grade, was significantly increased after treatment. In contrast, in Groups B and C, the treatment did not change the flow grade in the LAD. In Group A, the regional myocardial blood flow in the collateral dependent area was significantly increased after treatment, and the regional myocardial blood flow reserve after adenosine injection was also significantly increased. These measurements remained after treatment in Groups B and C. The immunohistochemical study with factor VIII-related antigen revealed an increase of vascular density in the ischemic region in Group A. Intramyocardial delivery of bFGF-impregnated AGHM, but not free-form bFGF, improves the collateral circulation to the infarct area of a coronary occlusion in dogs.

  17. Differentiation between acute and chronic myocardial infarction by means of texture analysis of late gadolinium enhancement and cine cardiac magnetic resonance imaging.

    PubMed

    Larroza, Andrés; Materka, Andrzej; López-Lereu, María P; Monmeneu, José V; Bodí, Vicente; Moratal, David

    2017-07-01

    The purpose of this study was to differentiate acute from chronic myocardial infarction using machine learning techniques and texture features extracted from cardiac magnetic resonance imaging (MRI). The study group comprised 22 cases with acute myocardial infarction (AMI) and 22 cases with chronic myocardial infarction (CMI). Cine and late gadolinium enhancement (LGE) MRI were analyzed independently to differentiate AMI from CMI. A total of 279 texture features were extracted from predefined regions of interest (ROIs): the infarcted area on LGE MRI, and the entire myocardium on cine MRI. Classification performance was evaluated by a nested cross-validation approach combining a feature selection technique with three predictive models: random forest, support vector machine (SVM) with Gaussian Kernel, and SVM with polynomial kernel. The polynomial SVM yielded the best classification performance. Receiver operating characteristic curves provided area-under-the-curve (AUC) (mean±standard deviation) of 0.86±0.06 on LGE MRI using 72 features; AMI sensitivity=0.81±0.08 and specificity=0.84±0.09. On cine MRI, AUC=0.82±0.06 using 75 features; AMI sensitivity=0.79±0.10 and specificity=0.80±0.10. We concluded that texture analysis can be used for differentiation of AMI from CMI on cardiac LGE MRI, and also on standard cine sequences in which the infarction is visually imperceptible in most cases. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Effects of high-intensity interval versus continuous moderate-intensity aerobic exercise on apoptosis, oxidative stress and metabolism of the infarcted myocardium in a rat model.

    PubMed

    Lu, Kai; Wang, Li; Wang, Changying; Yang, Yuan; Hu, Dayi; Ding, Rongjing

    2015-08-01

    The optimal aerobic exercise training (AET) protocol for patients following myocardial infarction (MI) has remained under debate. The present study therefore aimed to compare the effects of continuous moderate-intensity training (CMT) and high-intensity interval training (HIT) on cardiac functional recovery, and to investigate the potential associated mechanisms in a post-MI rat model. Female Sprague Dawley rats (8-10 weeks old) undergoing MI or sham surgery were subsequently submitted to CMT or HIT, or kept sedentary for eight weeks. Prior to and following AET, echocardiographic parameters and exercise capacity of the rats were measured. Western blotting was used to evaluate the levels of apoptosis and associated signaling pathway protein expression. The concentrations of biomarkers of oxidative stress were also determined by ELISA assay. Messenger (m)RNA levels and activity of the key enzymes for glycolysis and fatty acid oxidation, as well as the rate of adenosine triphosphate (ATP) synthesis, were also measured. Compared with the MI group, exercise capacity and cardiac function were significantly improved following AET, particularly following HIT. Left ventricular ejection fraction and fraction shortening were further improved in the MI-HIT group in comparison to that of the MI-CMT group. The two forms of AET almost equally attenuated apoptosis of the post-infarction myocardium. CMT and HIT also alleviated oxidative stress by decreasing the concentration of malondialdehyde and increasing the concentration of superoxide dismutase and glutathione peroxidase (GPx). In particular, HIT induced a greater increase in the concentration of GPx than that of CMT. AET, and HIT in particular, significantly increased the levels of mRNA and the maximal activity of phosphofructokinase-1 and carnitine palmitoyl transferase-1, as well as the maximal ratio of ATP synthesis. In addition, compared with the MI group, the expression of signaling proteins PI3K, Akt, p38mapk and AMPK

  19. Magnetic resonance imaging (MRI) of inflamed myocardium using iron oxide nanoparticles in patients with acute myocardial infarction - preliminary results.

    PubMed

    Yilmaz, Ali; Rösch, Sabine; Klingel, Karin; Kandolf, Reinhard; Helluy, Xavier; Hiller, Karl-Heinz; Jakob, Peter M; Sechtem, Udo

    2013-02-20

    Superparamagnetic iron oxide nanoparticle (SPIO)-based molecular imaging agents targeting macrophages have been developed and successfully applied in animal models of myocardial infarction. The purpose of this clinical trial was to investigate whether magnetic resonance imaging (MRI) of macrophages using ferucarbotran (Resovist®) allows improved visualisation of the myocardial (peri-)infarct zone compared to conventional gadolinium-based necrosis/fibrosis imaging in patients with acute myocardial infarction. The clinical study NIMINI-1 was performed as a prospective, non-randomised, non-blinded, single agent phase III clinical trial (NCT0088644). Twenty patients who had experienced either an acute ST-elevation or non-ST-elevation myocardial infarction (STEMI/NSTEMI) were included to this study. Following coronary angiography, a first baseline cardiovascular magnetic resonance (CMR) study (pre-SPIO) was performed within seven days after onset of cardiac symptoms. A second CMR study (post-SPIO) was performed either 10 min, 4h, 24h or 48h after ferucarbotran administration. The CMR studies comprised cine-CMR, T2-weighted "edema" imaging, T2-weighted cardiac imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging. The median extent of short-axis in-plane LGE was 28% (IQR 19-31%). Following Resovist® administration the median extent of short-axis in-plane T2-weighted hypoenhancement (suggestive of intramyocardial haemorrhage and/or SPIO accumulation) was 0% (IQR 0-9%; p=0.68 compared to pre-SPIO). A significant in-slice increase (>3%) in the extent of T2-weighted "hypoenhancement" (post-SPIO compared to pre-SPIO) was seen in 6/16 patients (38%). However, no patient demonstrated "hypoenhancement" in T2-weighted images following Resovist® administration that exceeded the area of LGE. T2/T2-weighted MRI aiming at non-invasive myocardial macrophage imaging using the approved dose of ferucarbotran does not allow improved visualisation of the myocardial (peri

  20. Transplantation of adipose tissue-derived stem cells overexpressing heme oxygenase-1 improves functions and remodeling of infarcted myocardium in rabbits.

    PubMed

    Yang, Jun-jie; Yang, Xia; Liu, Zhi-qiang; Hu, Shun-yin; Du, Zhi-yan; Feng, Lan-lan; Liu, Jian-feng; Chen, Yun-dai

    2012-01-01

    Adipose tissue-derived stem cells (ADSCs) are a promising source of autologous stem cells that are used for regeneration and repair of infracted heart. However, the efficiency of their transplantation is under debate. One of the possible reasons for marginal improvement in ADSCs transplantation is the significant cell death rate of implanted cells after being grafted into injured heart. Therefore, overcoming the poor survival rate of implanted cells may improve stem cell therapy. Due to limited improvement concerning direct stem cell therapy, gene-transfer methods are used to enhance cellular cardiomyoplasty efficacy. Heme oxygenase-1 (HO-1) can provide various types of cells with protection against oxidative injury and apoptosis. However, exact effects of autologous ADSCs combined with HO-1 on cardiac performance remains unknown. In this study, rabbits were treated with ADSCs transduced with HO-1 (HO-1-ADSCs), treated with non-transduced ADSCs, or injected with phosphate buffered saline 14 days after experimental myocardial infarction was induced, when autologous ADSCs were obtained simultaneously. Four weeks after injection, echocardiography showed significant improvements for cardiac functions and left ventricular dimensions in HO-1-ADSCs-treated animals. Structural consequences of transplantation were determined by detailed histological analysis, which showed differentiation of HO-1-ADSCs to cardiomyocyte-like tissues and lumen-like structure organizations. Apart from improvement in angiogenesis and scar areas, more connexin 43-positive gap junction and greater tyrosine hydroxylase-positive cardiac sympathetic nerves sprouting were observed in the HO-1-ADSCs-treated group compared with ADSCs group. These data suggest that the transplantation of autologous ADSCs combined with HO-1 transduction is a feasible and efficacious method for improving infarcted myocardium.

  1. Comparison between the collagen intensity and mast cell density in the lingual muscles and myocardium of autopsied chronic chagasic and nonchagasic patients.

    PubMed

    Roldão, José A; Beghini, Marcela; Ramalho, Luciana S; Porto, Carla Souza; Rodrigues, Denise B R; Teixeira, Vicente P A; de Lima Pereira, Sanívia A

    2012-08-01

    In chronic Chagas' disease (CD), an increase in collagen intensity and mast cell density has been described individually in the myocardium and tongue muscles. The aim of this study was to compare the percentage of collagen, mast cell tryptase (MCT) density, and mast cell chymase (MCH) density in the lingual muscles and myocardium from autopsied chagasic (CP) and nonchagasic patients (NCP). The selected cases were divided into two groups: (1) CP (n = 10) and (2) NCP (n = 10). Fragments were removed from the tongue and heart. After histological processing, the slices were stained with picrosirius, and immunohistochemistry was performed for MCH and MCT. The CP group showed the highest MCH and MCT densities and the highest percentage of collagen in the lingual muscles and myocardium when compared with the NCP group (p < 0.05). A significant positive correlation was observed between the collagen intensity and MCH density in the myocardium of the CP group. Although there are no reports in the literature of MCT and MCH in CD, its higher densities as well as higher percentage of collagen were found in the lingual muscles and myocardium in the CP group, suggesting that tryptase and chymase are associated with the pathogenesis of CD in these organs. Furthermore, the positive and significant correlation between the percentage of collagen and MCH density in the myocardium of the CP group suggests that the chymase is associated with fibrosis in CD, as demonstrated in other diseases.

  2. Cardiomyocyte Formation by Skeletal Muscle-Derived Multi-Myogenic Stem Cells after Transplantation into Infarcted Myocardium

    PubMed Central

    Tamaki, Tetsuro; Akatsuka, Akira; Okada, Yoshinori; Uchiyama, Yoshiyasu; Tono, Kayoko; Wada, Mika; Hoshi, Akio; Iwaguro, Hideki; Iwasaki, Hiroto; Oyamada, Akira; Asahara, Takayuki

    2008-01-01

    Background Cellular cardiomyoplasty for myocardial infarction has been developed using various cell types. However, complete differentiation and/or trans-differentiation into cardiomyocytes have never occurred in these transplant studies, whereas functional contributions were reported. Methods and Results Skeletal muscle interstitium-derived CD34+/CD45− (Sk-34) cells were purified from green fluorescent protein transgenic mice by flowcytometory. Cardiac differentiation of Sk-34 cells was examined by in vitro clonal culture and co-culture with embryonic cardiomyocytes, and in vivo transplantation into a nude rat myocardial infarction (MI) model (left ventricle). Lower relative expression of cardiomyogenic transcription factors, such as GATA-4, Nkx2-5, Isl-1, Mef2 and Hand2, was seen in clonal cell culture. However, vigorous expression of these factors was seen on co-culture with embryonic cardiomyocytes, together with formation of gap-junctions and synchronous contraction following sphere-like colony formation. At 4 weeks after transplantation of freshly isolated Sk-34 cells, donor cells exhibited typical cardiomyocyte structure with formation of gap-junctions, as well as intercalated discs and desmosomes, between donor and recipient and/or donor and donor cells. Fluorescence in situ hybridization (FISH) analysis detecting the rat and mouse genomic DNA and immunoelectron microscopy using anti-GFP revealed donor-derived cells. Transplanted Sk-34 cells were incorporated into infarcted portions of recipient muscles and contributed to cardiac reconstitution. Significant improvement in left ventricular function, as evaluated by transthoracic echocardiography and micro-tip conductance catheter, was also observed. Conclusions and Significance Skeletal muscle-derived multipotent Sk-34 cells that can give rise to skeletal and smooth muscle cells as reported previously, also give rise to cardiac muscle cells as multi-myogenic stem cells, and thus are a potential source for

  3. MIAT Is a Pro-fibrotic Long Non-coding RNA Governing Cardiac Fibrosis in Post-infarct Myocardium

    PubMed Central

    Qu, Xuefeng; Du, Yue; Shu, You; Gao, Ming; Sun, Fei; Luo, Shenjian; Yang, Ti; Zhan, Linfeng; Yuan, Yin; Chu, Wenfeng; Pan, Zhenwei; Wang, Zhiguo; Yang, Baofeng; Lu, Yanjie

    2017-01-01

    A long non-coding RNA (lncRNA), named myocardial infarction associated transcript (MIAT), has been documented to confer risk of myocardial infarction (MI). The aim of this study is to elucidate the pathophysiological role of MIAT in regulation of cardiac fibrosis. In a mouse model of MI, we found that MIAT was remarkably up-regulated, which was accompanied by cardiac interstitial fibrosis. MIAT up-regulation in MI was accompanied by deregulation of some fibrosis-related regulators: down-regulation of miR-24 and up-regulation of Furin and TGF-β1. Most notably, knockdown of endogenous MIAT by its siRNA reduced cardiac fibrosis and improved cardiac function and restored the deregulated expression of the fibrosis-related regulators. In cardiac fibroblasts treated with serum or angiotensin II, similar up-regulation of MIAT and down-regulation of miR-24 were consistently observed. These changes promoted fibroblasts proliferation and collagen accumulation, whereas knockdown of MIAT by siRNA or overexpression of miR-24 with its mimic abrogated the fibrogenesis. Our study therefore has identified MIAT as the first pro-fibrotic lncRNA in heart and unraveled the role of MIAT in the pathogenesis of MI. These findings also promise that normalization of MIAT level may prove to be a therapeutic option for the treatment of MI-induced cardiac fibrosis and the associated cardiac dysfunction. PMID:28198439

  4. Non-linear blending of dual-energy CT data improves depiction of late iodine enhancement in chronic myocardial infarction.

    PubMed

    Wichmann, Julian L; Hu, Xiaohan; Kerl, J Matthias; Schulz, Boris; Bodelle, Boris; Frellesen, Claudia; Lehnert, Thomas; Vogl, Thomas J; Bauer, Ralf W

    2014-08-01

    To compare non-linear and linear blending of cardiac dual-energy computed tomography (DECT) for optimal visualization of late iodine enhancement (LIE) in patients with chronic myocardial infarction (CMI). LIE-DECT data from 20 patients with known CMI were retrospectively analyzed. Images were reconstructed using non-linear blending center and width settings in the range of 0-500. Linear blending was performed with weighting factors 0.8 (80% 100 kV, 20% 140 kV), 0.6 and 0.3. 100-/140-kV data and blended images were analyzed. Contrast and percentage signal differences between infarcted and healthy myocardium and the left ventricle blood pool were computed. Statistical analysis was performed using repeated-measures analysis of variance and post hoc t tests. Non-linear blending showed the highest signal differences for all contrasts and analyses. Repeated-measures ANOVA tests confirmed the statistical differences between the investigated blending techniques (P < 0.01). Paired-samples post hoc t tests confirmed the significance of these results (P < 0.04). The ideal non-linear blending settings for best demarcation of CMI from healthy myocardium were a center of 65.8 ± 23.2 and a width of 0.0 ± 0.0. Non-linear blending of LIE-DECT improves display of LIE in patients with CMI in comparison with linear blending and non-post-processed image data from 100-/140-kV.

  5. Hibernating myocardium results in partial sympathetic denervation and nerve sprouting

    PubMed Central

    Fernandez, Stanley F.; Ovchinnikov, Vladislav; Canty, John M.

    2013-01-01

    Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (−32%, P < 0.001), norepinephrine uptake transport protein (−25%, P = 0.01), and tissue norepinephrine content (−45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors. PMID:23125211

  6. The 'silence' of silent brain infarctions may be related to chronic ischemic preconditioning and nonstrategic locations rather than to a small infarction size.

    PubMed

    Feng, Chao; Bai, Xue; Xu, Yu; Hua, Ting; Liu, Xue-Yuan

    2013-01-01

    Silent brain infarctions are the silent cerebrovascular events that are distinguished from symptomatic lacunar infarctions by their 'silence'; the origin of these infarctions is still unclear. This study analyzed the characteristics of silent and symptomatic lacunar infarctions and sought to explore the mechanism of this 'silence'. In total, 156 patients with only silent brain infarctions, 90 with only symptomatic lacunar infarctions, 160 with both silent and symptomatic lacunar infarctions, and 115 without any infarctions were recruited. Vascular risk factors, leukoaraiosis, and vascular assessment results were compared. The National Institutes of Health Stroke Scale scores were compared between patients with only symptomatic lacunar infarctions and patients with two types of infarctions. The locations of all of the infarctions were evaluated. The evolution of the two types of infarctions was retrospectively studied by comparing the infarcts on the magnetic resonance images of 63 patients obtained at different times. The main risk factors for silent brain infarctions were hypertension, age, and advanced leukoaraiosis; the main factors for symptomatic lacunar infarctions were hypertension, atrial fibrillation, and atherosclerosis of relevant arteries. The neurological deficits of patients with only symptomatic lacunar infarctions were more severe than those of patients with both types of infarctions. More silent brain infarctions were located in the corona radiata and basal ganglia; these locations were different from those of the symptomatic lacunar infarctions. The initial sizes of the symptomatic lacunar infarctions were larger than the silent brain infarctions, whereas the final sizes were almost equal between the two groups. Chronic ischemic preconditioning and nonstrategic locations may be the main reasons for the 'silence' of silent brain infarctions.

  7. Cardiovascular magnetic resonance of the myocardium at risk in acute reperfused myocardial infarction: comparison of T2-weighted imaging versus the circumferential endocardial extent of late gadolinium enhancement with transmural projection

    PubMed Central

    2010-01-01

    Background In the situation of acute coronary occlusion, the myocardium supplied by the occluded vessel is subject to ischemia and is referred to as the myocardium at risk (MaR). Single photon emission computed tomography has previously been used for quantitative assessment of the MaR. It is, however, associated with considerable logistic challenges for employment in clinical routine. Recently, T2-weighted cardiovascular magnetic resonance (CMR) has been introduced as a new method for assessing MaR several days after the acute event. Furthermore, it has been suggested that the endocardial extent of infarction as assessed by late gadolinium enhanced (LGE) CMR can also be used to quantify the MaR. Hence, we sought to assess the ability of endocardial extent of infarction by LGE CMR to predict MaR as compared to T2-weighted imaging. Methods Thirty-seven patients with early reperfused first-time ST-segment elevation myocardial infarction underwent CMR imaging within the first week after percutaneous coronary intervention. The ability of endocardial extent of infarction by LGE CMR to assess MaR was evaluated using T2-weighted imaging as the reference method. Results MaR determined with T2-weighted imaging (34 ± 10%) was significantly higher (p < 0.001) compared to the MaR determined with endocardial extent of infarction (23 ± 12%). There was a weak correlation between the two methods (r2 = 0.17, p = 0.002) with a bias of -11 ± 12%. Myocardial salvage determined with T2-weighted imaging (58 ± 22%) was significantly higher (p < 0.001) compared to myocardial salvage determined with endocardial extent of infarction (45 ± 23%). No MaR could be determined by endocardial extent of infarction in two patients with aborted myocardial infarction. Conclusions This study demonstrated that the endocardial extent of infarction as assessed by LGE CMR underestimates MaR in comparison to T2-weighted imaging, especially in patients with early reperfusion and aborted myocardial

  8. [Differential gene expression profile in ischemic myocardium of Wistar rats with acute myocardial infarction: the study on gene construction, identification and function].

    PubMed

    Guo, Chun Yu; Yin, Hui Jun; Jiang, Yue Rong; Xue, Mei; Zhang, Lu; Shi, Da Zhuo

    2008-06-18

    To construct the differential genes expressed profile in the ischemic myocardium tissue reduced from acute myocardial infarction(AMI), and determine the biological functions of target genes. AMI model was generated by ligation of the left anterior descending coronary artery in Wistar rats. Total RNA was extracted from the normal and the ischemic heart tissues under the ligation point 7 days after the operation. Differential gene expression profiles of the two samples were constructed using Long Serial Analysis of Gene Expression(LongSAGE). Real time fluorescence quantitative PCR was used to verify gene expression profile and to identify the expression of 2 functional genes. The activities of enzymes from functional genes were determined by histochemistry. A total of 15,966 tags were screened from the normal and the ischemic LongSAGE maps. The similarities of the sequences were compared using the BLAST algebra in NCBI and 7,665 novel tags were found. In the ischemic tissue 142 genes were significantly changed compared with those in the normal tissue (P<0.05). These differentially expressed genes represented the proteins which might play important roles in the pathways of oxidation and phosphorylation, ATP synthesis and glycolysis. The partial genes identified by LongSAGE were confirmed using real time fluorescence quantitative PCR. Two genes related to energy metabolism, COX5a and ATP5e, were screened and quantified. Expression of two functional genes down-regulated at their mRNA levels and the activities of correlative functional enzymes decreased compared with those in the normal tissue. AMI causes a series of changes in gene expression, in which the abnormal expression of genes related to energy metabolism could be one of the molecular mechanisms of AMI. The intervention of the expressions of COX5a and ATP5e may be a new target for AMI therapy.

  9. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    SciTech Connect

    Waksman, Ron; Baffour, Richard

    2003-09-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell.

  10. Lack of cardiac nerve sprouting after intramyocardial transplantation of bone marrow-derived stem cells in a swine model of chronic ischemic myocardium.

    PubMed

    Liu, Yuan; Lai, Wing-Hon; Liao, Song-Yan; Siu, Chung-Wah; Yang, Yan-Zong; Tse, Hung-Fat

    2012-06-01

    Previous experimental studies suggested that mesenchymal stem cell transplantation causes cardiac nerve sprouting; however, whether bone marrow (BM)-derived mononuclear cells (MNC) and endothelial progenitor cells (EPC) can also lead to cardiac nerve sprouting and alter gap junction expression remains unclear. We investigated the effect of electroanatomical mapping-guided direct intramyocardial transplantation of BM-MNC (n = 8) and CD31+EPC (n = 8) compared with saline control (n = 8) on cardiac nerve sprouting and gap junction expression in a swine model of chronic ischemic myocardium. At 12 weeks after transplantation, the distribution and density of cardiac nerve sprouting were determined by staining of tyrosine hydroxylase (TH) and growth associated protein 43(GAP-43) and expression of connexin 43 in the targeted ischemic and remote normal myocardium. After 12 weeks, no animal developed sudden death after the transplantation. There were no significant differences in the number of cells with positive staining of TH and GAP-43 in the ischemic and normal myocardium between three groups. Furthermore, expression of connexin 43 was also similar in the ischemic and normal myocardia in each group of animals (P > 0.05). The results of this study demonstrated that intramyocardial BM-derived MNC or EPC transplantation in a large animal model of chronic myocardial ischemia was not associated with increased cardiac nerve sprouting over the ischemic myocardium.

  11. Smad3 inactivation and MiR-29b upregulation mediate the effect of carvedilol on attenuating the acute myocardium infarction-induced myocardial fibrosis in rat.

    PubMed

    Zhu, Jie-Ning; Chen, Ren; Fu, Yong-Heng; Lin, Qiu-Xiong; Huang, Shuai; Guo, Lin-Lin; Zhang, Meng-Zhen; Deng, Chun-Yu; Zou, Xiao; Zhong, Shi-Long; Yang, Min; Zhuang, Jian; Yu, Xi-Yong; Shan, Zhi-Xin

    2013-01-01

    Carvedilol, a nonselective β-adrenoreceptor antagonist, protects against myocardial injury induced by acute myocardium infarction (AMI). The mechanisms underlying the anti-fibrotic effects of carvedilol are unknown. Recent studies have revealed the critical role of microRNAs (miRNAs) in a variety of cardiovascular diseases. This study investigated whether miR-29b is involved in the cardioprotective effect of carvedilol against AMI-induced myocardial fibrosis. Male SD rats were randomized into several groups: the sham surgery control, left anterior descending (LAD) surgery-AMI model, AMI plus low-dose carvedilol treatment (1 mg/kg per day, CAR-L), AMI plus medium-dose carvedilol treatment (5 mg/kg per day, CAR-M) and AMI plus high-dose carvedilol treatment (10 mg/kg per day, CAR-H). Cardiac remodeling and impaired heart function were observed 4 weeks after LAD surgery treatment; the observed cardiac remodeling, decreased ejection fraction, and fractional shortening were rescued in the CAR-M and CAR-H groups. The upregulated expression of Col1a1, Col3a1, and α-SMA mRNA was significantly reduced in the CAR-M and CAR-H groups. Moreover, the downregulated miR-29b was elevated in the CAR-M and CAR-H groups. The in vitro study showed that Col1a1, Col3a1, and α-SMA were downregulated and miR-29b was upregulated by carvedilol in a dose-dependent manner in rat cardiac fibroblasts. Inhibition of ROS-induced Smad3 activation by carvedilol resulted in downregulation of Col1a1, Col3a1, and α-SMA and upregulation of miR-29b derived from the miR-29b-2 precursor. Enforced expression of miR-29b significantly suppressed Col1a1, Col3a1, and α-SMA expression. Taken together, we found that smad3 inactivation and miR-29b upregulation contributed to the cardioprotective activity of carvedilol against AMI-induced myocardial fibrosis.

  12. Effect of mild aerobic training on the myocardium of mice with chronic Chagas disease

    PubMed Central

    Preto, Emerson; Lima, Nathalia EA; Simardi, Lucila; Fonseca, Fernando Luiz Affonso; Filho, Abílio Augusto Fragata; Maifrino, Laura Beatriz Mesiano

    2015-01-01

    Background Chronic chagasic heart disease represents extensive remodeling of the cardiovascular system, manifested as cardiac denervation, interstitial mononuclear infiltrate, myocyte and vascular degenerative changes, fibrosis, and hypertrophy. Moreover, aerobic exercises are widely indicated for the treatment of various disorders of the cardiovascular system. Purpose To evaluate the right and left ventricles of BALB/c mice with chronic Chagas disease, undergoing mild exercise, by using morphometric and stereological methods. Materials and methods A total of 20 male mice at 4 months of age were used for experiments. The animals were divided into four groups (n=5 in each group): untrained control, trained control, untrained infected (UI), and trained infected (TI). Animals of UI and TI groups were inoculated with 1,000 trypomastigote forms of Trypanosoma cruzi (Y strain), and after 40 days, animals entered chronic phase of the disease. Physical exercise, which included swimming, was performed for 30 minutes daily, five times a week for 8 consecutive weeks at a bath temperature of 30°C. After the trial period, euthanasia and subsequent withdrawal of the heart were done. The organ was prepared by histological staining procedures with hematoxylin–eosin and picrosirius red. Results We found that the physical training used in our experimental model promoted increase in volume density of capillaries and decrease in volume density of collagen fibers and cross-sectional area of cardiomyocytes in chagasic animals (TI group). By histopathological analysis, we found differences in the inflammatory infiltrate, which was lower in animals of TI group. The training program promoted a recovery of these parameters in the TI group. Conclusion Our results suggest that low-intensity aerobic exercise acts on morphological and morphometric parameters of the left and right ventricles in mice infected with T. cruzi, reducing the changes caused by the organism and making the results

  13. Na+-K+ pump inhibition caused by chronic amiodarone in guinea pig myocardium.

    PubMed

    Maruyama, T; Ueda, N; Kaji, Y; Kanaya, S; Fujino, T; Niho, Y

    1999-01-01

    Although it is known that amiodarone inhibits myocardial Na+-K+ pump activity, the potency and the time course of this inhibition are unknown. The aim of this study was to investigate these aspects with reference to digoxin, using guinea pigs treated with either intraperitoneal amiodarone (20mg/kg per week, up to 12 weeks, n = 26) or the same amount of vehicle as a control (n = 24). ECG recording and microelectrode experiments were conducted every 2 weeks. QT interval corrected by heart rate and action potential duration were prolonged as a function of the time of exposure to amiodarone. Hyperpolarization observed immediately after the overdrive (1.0Hz) termination or K+-replenishment following K+-depletion in the presence of 0.1mM Ba2+ was compared in the amiodarone-treated and untreated groups, as an index of the Na+-K+ pump activity. The resting membrane potential recovery from overdrive-induced depolarization was slower and the amplitude of K+-induced hyperpolarization was smaller in the amiodarone-treated group than in the untreated group. These changes were evident as the chronic amiodarone treatment progressed, although the changes in these parameters were greater in the case of acute application of 50 microM digoxin. In conclusion, this study indicates that treatment with amiodarone for longer than several weeks moderately inhibits the myocardial Na+-K+ pump.

  14. Identification of residual viable tissue in chronic ECG Q wave infarcts with positron emission tomography

    SciTech Connect

    Brunken, R.; Tillisch, J.; Schwaiger, M.; Child, J.; Marshall, R.; Phelps, M.; Schelbert, H.

    1985-05-01

    Although electrocardiographic Q waves have routinely been associated with transmural infarction, even small subendocardial infarctions may result in Q waves. The authors postulated that some chronic Q wave infarct regions might exhibit preserved metabolic activity on postron emission tomography (PET) with N-13 ammonia (NH3) and F-18 deoxyglucose (FDG). Twenty patients with 31 Q wave infarct regions (11 septal, 7 anterior, 3 lateral, and 10 inferoposterior) were studied. PET ischemia was defined as a discordant increase in FDG activity relative to NH3, while PET infarction was defined as a concordant reduction in both FDG and NH3 activity. The observed PET patterns were correlated with regional wall motion as assessed by independent observers on LV gram, 2D echo or radionuclide angiogram. There was a significant difference in wall motion score between regions that were normal on PET and those that were ischemic or infarcted on PET. No difference in wall motion was noted between regions with PET ischemia and PET infarction. Thus, PET reveals residual metabolic activity in a high proportion of Q wave infarct regions (68%) and analysis of wall motion does not allow differentiation between ischemic and infarcted regions.

  15. Stress and vitamin D: altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats.

    PubMed

    Jiang, Pei; Zhang, Wen-Yuan; Li, Huan-De; Cai, Hua-Lin; Liu, Yi-Ping; Chen, Lin-Yao

    2013-10-01

    Exposure to stressful life events is associated with the onset of major depression and increases the risk of cardiac morbidity and mortality. While recent evidence has indicated the existence of an interrelationship between local vitamin D (VD) metabolism and many aspects of human physiology including brain and heart function, much is still unknown concerning the biological link between VD signaling and stress-induced depressive behavior and cardiac dysfunction. In the present study, we observed the VD intracrine system in the hippocampus and myocardium of chronic unpredictable mild stress (CUMS) exposed rats. After 4 weeks of CUMS procedure, rats were induced to a depressive-like state and the cytochromes P450 enzymes involved in VD activating and catabolizing (CYP27B1 and CYP24A1 respectively) and VD receptor (VDR) were assessed by real time RT-PCR and western blot in the hippocampus, myocardium and kidney. In the hippocampus of depressed rats, CYP27B1, CYP24A1 and VDR expression were significantly increased and the local status of 1,25-dihydroxyvitamin D (1,25(OH)2D) was higher compared with controls. Furthermore, hippocampal mRNA levels of VD target genes (calbindin-d28k, neurotrophin-3) and RXRα (heterodimeric partner of VDR) were upregulated in response to chronic stress. Similar to the hippocampus, CUMS also induced CYP27B1/CYP24A1/VDR expression in the myocardium. However, renal metabolism of VD and serum1,25(OH)2D status were unchanged. Meanwhile, sertraline treatment could partly normalize the stress-induced alterations of VD metabolism. In conclusion, this study firstly showed a co-elevated expression of CYP27B1/CYP24A1/VDR in both the hippocampus and myocardium of CUMS rats, which suggests VD signaling may be involved in the compensatory mechanism that protect from stress-induced deteriorating effects on the brain and heart.

  16. Acute lacunar infarcts in CLIPPERS: is the chronic infiltrative lymphocytic perivascular disease process to blame?

    PubMed

    Saigal, Gaurav; Quencer, Robert

    2013-12-01

    CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process.

  17. Acute Lacunar Infarcts in CLIPPERS: Is the Chronic Infiltrative Lymphocytic Perivascular Disease Process to Blame?

    PubMed Central

    Saigal, Gaurav; Quencer, Robert

    2013-01-01

    Summary CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process. PMID:24355180

  18. Renal infarct volume and renal function decline in acute and chronic phases.

    PubMed

    Kagaya, Saeko; Yoshie, Ojima; Fukami, Hirotaka; Sato, Hiroyuki; Saito, Ayako; Takeuchi, Yoichi; Matsuda, Ken; Nagasawa, Tasuku

    2017-03-10

    Acute renal infarction (ARI) is a rare disease. ARI causes decline in renal function in both the acute and chronic phases. However, the correlation between the volume of the infarction and degree of renal function decline has not been fully investigated. Therefore, we aimed to examine the relationship between the volume of the infarction and degree of renal function decline. We performed a single-center, retrospective, observational study investigating clinical parameters and the volume of the infarction. The volume of the infarction was measured using reconstructed computed tomography data. A total of 39 patients (mean age, 72.6 ± 13.2 years; men, 59%) were enrolled. The median infarction volume was 45 mL (interquartile range, 14-91 mL). The volume of the infarction was significantly associated with the peak lactate dehydrogenase (LDH) level (median, 728 IU/L; interquartile range, 491-1227 U/L) (r = 0.58, p < 0.01) and the degree of renal function decline in both acute and chronic phases (r = -0.44, -0.38, respectively, p < 0.05). The peak LDH level was significantly correlated with the degree of renal function decline in the acute phase but not in the chronic phase (r = -0.35, -0.21; p < 0.05, N.S., respectively). The volume of the infarction may be a factor in the degree of renal function decline in ARI. Therefore, assessment of infarct volume in ARI is important.

  19. Chronic left atrial volume overload abbreviates the action potential duration of the canine pulmonary vein myocardium via activation of IK channel.

    PubMed

    Nouchi, Hideaki; Takahara, Akira; Nakamura, Hideki; Namekata, Iyuki; Sugimoto, Takahiko; Tsuneoka, Yayoi; Takeda, Kiyoshi; Tanaka, Toshikazu; Shigenobu, Koki; Sugiyama, Atsushi; Tanaka, Hikaru

    2008-11-12

    Electrophysiological properties of the pulmonary vein myocardium were assessed in a canine chronic atrioventricular block model resulting in left atrial volume overload. Five chronic atrioventricular block dogs and five sham-operated dogs were used. The heart was removed two months after a surgical procedure causing atrioventricular block, when atrial structural remodeling was established. Standard microelectrode penetrations were made with glass microelectrodes to obtain action potential signals of left atrium and pulmonary vein myocardia. The resting membrane potential in the pulmonary vein was more positive than that in the left atrium (-69 mV vs -74 mV) in both animal groups. The action potential duration at 50% repolarization of the pulmonary vein was shorter in the chronic atrioventricular block dogs than in the sham-operated dogs (38 ms vs 63 ms), whereas no significant difference was detected in the action potential duration of the left atrium between the two animal groups (67 ms vs 61 ms). The action potential duration of the pulmonary vein in the chronic atrioventricular block dogs was prolonged by charybdotoxin but not by iberiotoxin. Such prolongation was not observed in the normal pulmonary vein. These results suggest that long-term left atrial dilatation shortened the action potential duration of pulmonary vein myocardium, which may be associated with activation of the intermediate conductance Ca2+-activated K+ channel (IK channel).

  20. Chronic effects of myocardial infarction on right ventricular function: a noninvasive assessment

    SciTech Connect

    Kaul, S.; Hopkins, J.M.; Shah, P.M.

    1983-10-01

    To assess the chronic effects of myocardial infarction on right ventricular function, 48 subjects were studied utilizing radionuclide angiography and two-dimensional echocardiography. Ten were normal subjects (group I), 11 had previous inferior wall myocardial infarction (group II), 10 had previous anteroseptal infarction (group III), 11 had combined anteroseptal and inferior infarction (group IV) and 6 had extensive anterolateral infarction (group V). The mean (+/- standard deviation) left ventricular ejection fraction was 0.66 +/- 0.03 in group I, 0.58 +/- 0.02 in group II, 0.52 +/- 0.02 in group III, 0.33 +/- 0.03 in group IV and 0.33 +/- 0.01 in group V. No systematic correlation between left and right ventricular ejection fraction was observed among the groups. The mean right ventricular ejection fraction was significantly reduced in the presence of inferior myocardial infarction (0.30 +/- 0.03 in group II and 0.29 +/- 0.03 in group IV compared with 0.43 +/- 0.02 in group I (p less than 0.001)). The group II and IV patients also had increased (p less than 0.001) right ventricular end-diastolic area and decreased (p less than 0.001) right ventricular free wall motion by two-dimensional echocardiography. In the presence of anteroseptal infarction (group III), right ventricular free wall motion was increased (p less than 0.05) compared with normal subjects (group I). Thus, the effects of prior myocardial infarction on right ventricular function depend more on the location of infarction than on the extent of left ventricular dysfunction. Inferior infarction was commonly associated with reduced right ventricular ejection fraction and increased right ventricular end-diastolic area. The right ventricular free wall excursion was increased in the presence of anteroseptal infarction, suggested loss of contribution of interventricular septal contraction to right ventricular ejection.

  1. Significance of both negative T waves and stress-induced normalization of the repolarization phase in infarcted patients: a positron-emission-tomography assessment of regulation of myocardial blood flow and viability of myocardium.

    PubMed

    Giorgetti, A; Sambuceti, G; Neglia, D; Sorace, O; Salvadori, P A; Parodi, O

    2001-05-01

    The clinical correlation of stress-induced normalization of previously negative T waves (NNTW) to regulation of regional myocardial blood flow (MBF) and tissue viability is still being debated. To clarify its meaning. We studied 25 patients, who had previously suffered anterior myocardial infarction and for whom negative T waves were recorded on baseline electrocardiographic precordial leads, by means of positron emission tomography. We obtained MBF in the infarcted myocardial regions under resting conditions for all patients, during infusion of dipyridamole (17 patients) and dobutamine (20 patients), using [13N]-ammonia as a flow tracer. During stress tests, 13 patients exhibited NNTW (group 1) whereas the remaining 12 presented persistent negative T waves (group 2). NNTW was observed in 18 stress studies (for 10 and eight patients during administration of dobutamine and dipyridamole, respectively) whereas persistent negative T waves occurred 19 times (for 10 patients during infusion of dobutamine and nine patients during administration of dipyridamole). A complete concordance of the modifications of the repolarization phase was observed for patients who were subjected both to dipyridamole and to dobutamine studies. Furthermore, we assessed viability of myocardium in 20 of 25 patients using [18F]-fluorodeoxyglucose. For the remaining five patients not subjected to metabolic imaging, a coronary reserve of 1.65 was considered a cut-off of viability. Resting MBF for patients in groups 1 and 2 were similar (0.53 +/- 0.20 versus 0.47 +/- 0.17 ml/min per g, respectively, NS) whereas during pharmacological stress, MBF of patients in group 1 was significantly higher than that for patients in group 2 (0.99 +/- 0.41 versus 0.56 +/- 0.26 ml/min per g, respectively, P < 0.0001). Coronary vasodilating capability, expressed as stress/resting MBF ratio, turned out to be 1.88 +/- 0.49 and 1.16 +/- 0.37 for patients in groups 1 and 2, respectively (P < 0.0001). We observed no

  2. Treatment of Chronic Myocardial Infarction in a Pig (Sus scrofa) Model with Extracellular Matrix and Stem Cells

    DTIC Science & Technology

    2015-08-13

    Use additional pages If necessary.) PROTOCOL #: FDG20140039A DATE: 13 August 2015 PROTOCOL TITLE: Treatment of Chronic Myocardial Infarction in a...model developed in protocols FDG20120019A and FDG20130043A, we were able to successfully create myocardial infarctions in pigs with a high survival rate...applications.) ObJectives: The goal of this protocol was to create myocardial infarctions in miniplgs using polystyrene microspheres to Infarct a

  3. Comparison of early exercise treadmill test and oral dipyridamole thallium-201 tomography for the identification of jeopardized myocardium in patients receiving thrombolytic therapy for acute Q-wave myocardial infarction

    SciTech Connect

    Jain, A.; Hicks, R.R.; Frantz, D.M.; Myers, G.H.; Rowe, M.W. )

    1990-09-01

    Thrombolytic therapy has become the treatment of choice for patients with acute myocardial infarction. Researchers are not yet able to identify patients with salvage of myocardium who are at risk for recurrent coronary events. Thus, a prospective trial was performed in 46 patients with myocardial infarction (28 anterior and 18 inferior) who received thrombolytic therapy to determine if early thallium tomography (4.7 days) using oral dipyridamole would identify more patients with residual ischemia than early symptom-limited exercise treadmill tests (5.5 days). There were no complications during the exercise treadmill tests or oral dipyridamole thallium tomography. Mean duration of exercise was 11 +/- 3 minutes and the peak heart rate was 126 beats/min. Thirteen patients had positive test results. After oral dipyridamole all patients had abnormal thallium uptake on the early images. Positive scans with partial filling in of the initial perfusion defects were evident in 34 patients. Angina developed in 13 patients and was easily reversed with intravenous aminophylline. Both symptom-limited exercise treadmill tests and thallium tomography using oral dipyridamole were safely performed early after myocardial infarction in patients receiving thrombolytic therapy. Thallium tomography identified more patients with residual ischemia than exercise treadmill tests (74 vs 28%). Further studies are required to determine whether the results of thallium tomography after oral dipyridamole can be used to optimize patient management and eliminate the need for coronary angiography in some patients.

  4. Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease.

    PubMed

    Falk, Torkel; Jönsson, Lennart; Olsen, Lisbeth H; Pedersen, Henrik D

    2006-01-01

    The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. Twenty-one dogs with naturally occurring congestive heart failure and 21 age-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta and pulmonary artery. Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (P < .003), lung (P < .0001), and kidney (P < .02); intimal-medial thickening in the pulmonary artery (P = .04); and fibrosis in the left ventricle (P < .0001) than control dogs. However, they did not have more plaque formation or intimal-medial thickening in the aorta than controls. There was significantly more arterial narrowing in papillary muscles than in all other locations in dogs with congestive heart failure (P < .002). In control dogs, arterial changes were less pronounced and did not differ in different locations. Dogs with naturally occurring myxomatous mitral valve disease have significantly more arterial changes in the myocardium, lung, and kidney, and significantly more fibrosis in the myocardium than control dogs. This could have important implications in the management of myxomatous mitral valve disease and raises interesting questions about the occurrence and importance of intramural small vessel disease in humans with primary mitral valve prolapse.

  5. ["Myocardium in hibernation"--implications for clinical medicine].

    PubMed

    Auer, J; Berent, R; Eber, B

    2000-01-01

    Myocardial infarction is one of the leading causes of heart failure. Medical therapy of heart failure is effective in reduction of morbidity and mortality. In spite of intensive pharmacological and non-pharmacological treatment, prognosis of advanced heart failure remains poor. Fibrinolytics and other adjuvant medical strategies have improved prognosis of acute myocardial infarction with a significant reduction in mortality and morbidity. 40% of myocardial segments involved in acute ischemia during myocardial infarction show characteristics of postischemic functional disorder and contraction abnormalities despite reperfusion. Recovery can be observed in the following period spontaneously or after revascularisation procedures when chronic ischemic myocardium can be detected. Presence of viable jeopardized myocardium worsens prognosis and overall outcome in patients with myocardial ischemia and impaired left ventricular function. Revascularisation procedures improve angina functional class, symptoms from heart failure, exercise capacity and survival in patients with impaired left ventricular ejection fraction in the presence of severe coronary artery stenoses and viability of myocardial segments with ischemia-induced contractile dysfunction.

  6. [Effects of intravenous transplantation of human umbilical cord blood mononuclear cells combined compound Danshen dripping pills on the microenvironment and apoptosis in the myocardium of the rabbits with acute myocardial infarction].

    PubMed

    Yuan, Chunjun; Ai, Qi; Deng, Liuxia; Yu, Guolong

    2013-08-01

    To explore the effects of compound Danshen dripping pills (CDDP) and CDDP combined with transplantation of human umbilical cord blood cells (HUMNCs) on the inflammatory response, oxidative stress, myocardial cell apoptosis and cardiac function, and also to investigate the possible mechanisms of the combined therapy in the acute myocardial infarction (AMI). Rabbit model of AMI successfully established by ligation of the left anterior coronary artery (LAD). Forty rabbits were randomly divided into 4 groups (n=10 per group): a control group, injected with 0.5 mL of saline in 24 h after AMI and then gavaged with 5 mL of saline daily; a CDDP group, injected with saline 0.5 mL after AMI and then gavaged with CDDP (270 mg/d) daily; a transplantation group, injected with 0.5 mL of saline contained 3 × 10(7) HUCBMCs [labeled with green fluorescent protein (GFP)] and then gavaged with 5 mL of saline daily; a combined group, injected with 0.5 mL of saline contained 3 × 10(7) HUCBMCs (labeled with GFP) and then gavaged with CDDP (270 mg/d) daily. Cardiac function index such as left ventricular fractional shorting (LVFS) and ejection fraction(LVEF) were measured by echocardiography; the pathological changes were observed by HE staining and the white blood cells in the myocardium were determined by light microscopy. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium were detected by nitrotetrazolium blue chloride (NBT) and thiobarbituric acid colorimetric measurement respectively. The number of transplanted cells in the myocardium was examined by GFP positive cells counted with fluorescence microscopy. 1) Compared with the control group (at 1 or 4 week), LVEF and LVFS were significant improved in the CDDP group, the transplantation group and the combined groups (all P<0.05), the improvement degree of cardiac function in the combined group was the most significance. There was no significant difference between the CDDP group and the

  7. Reproducibility of chronic infarct size measurement by contrast-enhanced magnetic resonance imaging.

    PubMed

    Mahrholdt, Heiko; Wagner, Anja; Holly, Thomas A; Elliott, Michael D; Bonow, Robert O; Kim, Raymond J; Judd, Robert M

    2002-10-29

    The reproducibility of contrast-enhanced MRI has not been established. We compared MRI reproducibility for infarct size determination with that of (99m)Tc-sestamibi (MIBI) single photon emission computed tomography (SPECT). Patients with chronic myocardial infarction defined by enzymes (peak creatine kinase-MB 173+/-119 U/L) were scanned twice by MRI (MRI I and MRI II, n=20) and twice by SPECT (SPECT I and SPECT II, n=15) on the same day. The MRI contrast agent was injected during MRI I but not MRI II to test the effect of imaging time after contrast. Resting Tc-MIBI SPECT images were acquired and infarct size was determined with commercial software. Infarct size in patients scanned by MRI and SPECT was 14+/-6% of left ventricular mass (%LV) by MRI (range 4%LV to 27%LV) and 14+/-7%LV by SPECT (range 4%LV to 26%LV). MRI I and II scans were performed 10+/-2 and 27+/-3 minutes after contrast, respectively. For MRI, the difference in infarct size between scans I and II (bias) was -0.1%LV, and the coefficient of repeatability was +/-2.4%LV. For SPECT, bias was -1.3%LV, and the coefficient of repeatability was +/-4.0%LV. Within individual patients, no systematic differences in infarct size were detected when the 2 MRI scans were compared, the 2 SPECT scans were compared, or MRI was compared to SPECT. The size of healed infarcts measured by contrast-enhanced MRI does not change between 10 and 30 minutes after contrast. The clinical reproducibility of contrast-enhanced MRI for infarct size determination compares favorably with that of routine clinical SPECT.

  8. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model.

    PubMed

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-Ichiro; Egashira, Kensuke

    2016-01-01

    There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic modality for IR injury in acute myocardial

  9. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model

    PubMed Central

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-ichiro; Egashira, Kensuke

    2016-01-01

    Background There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Methods and Results Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. Conclusions NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic

  10. Dual extradural cortical stimulation in chronic stroke patients with large infarcts: technical case report.

    PubMed

    Shin, Yong-Il; Kim, Hyoungihl; Moon, Seong-Keun; Kim, Hyojoon; Yun, Yong-Soon; Chung, Gyung-Ho

    2010-06-01

    Recent works on extradural cortical stimulation have been successful in improving neurological recovery in chronic stroke patients. On the other hand, single perirolandic stimulations are often associated with disappointing results. We report two cases of chronic stroke in which the magnitude of infarct was too large to be improved with single perirolandic stimulation. Patient 1 had severe hemiplegia associated with large cortical infarct in the right frontoparietal area. The patient could neither stand independently or walk. Patient 2 had hemiplegia and aphasia due to cortical infarct in the left middle cerebral artery territory. Both patients had intensive rehabilitative training for more than 6 months with no beneficial results. Two paddle electrodes covering frontal and parietal area were implanted, followed by dual cortical stimulation with concurrent rehabilitative training in patient 1. After 6 months of stimulation, the patient could walk with a good posture. Two paddle electrodes were implanted to cover pre-motor and motor cortex in patient 2. After similar treatment, the motor function was markedly improved. Dual cortex stimulation, which acts on more diffuse areas or functionally related areas, is beneficial to promote the motor recovery in chronic stroke patients with large infarcts.

  11. Quantification of myocardium at risk in ST- elevation myocardial infarction: a comparison of contrast-enhanced steady-state free precession cine cardiovascular magnetic resonance with coronary angiographic jeopardy scores.

    PubMed

    De Palma, Rodney; Sörensson, Peder; Verouhis, Dinos; Pernow, John; Saleh, Nawzad

    2017-07-27

    Clinical outcome following acute myocardial infarction is predicted by final infarct size evaluated in relation to left ventricular myocardium at risk (MaR). Contrast-enhanced steady-state free precession (CE-SSFP) cardiovascular magnetic resonance imaging (CMR) is not widely used for assessing MaR. Evidence of its utility compared to traditional assessment methods and as a surrogate for clinical outcome is needed. Retrospective analysis within a study evaluating post-conditioning during ST elevation myocardial infarction (STEMI) treated with coronary intervention (n = 78). CE-SSFP post-infarction was compared with angiographic jeopardy methods. Differences and variability between CMR and angiographic methods using Bland-Altman analyses were evaluated. Clinical outcomes were compared to MaR and extent of infarction. MaR showed correlation between CE-SSFP, and both BARI and APPROACH scores of 0.83 (p < 0.0001) and 0.84 (p < 0.0001) respectively. Bias between CE-SSFP and BARI was 1.1% (agreement limits -11.4 to +9.1). Bias between CE-SSFP and APPROACH was 1.2% (agreement limits -13 to +10.5). Inter-observer variability for the BARI score was 0.56 ± 2.9; 0.42 ± 2.1 for the APPROACH score; -1.4 ± 3.1% for CE-SSFP. Intra-observer variability was 0.15 ± 1.85 for the BARI score; for the APPROACH score 0.19 ± 1.6; and for CE-SSFP -0.58 ± 2.9%. Quantification of MaR with CE-SSFP imaging following STEMI shows high correlation and low bias compared with angiographic scoring and supports its use as a reliable and practical method to determine myocardial salvage in this patient population. Clinical trial registration information for the parent clinical trial: Karolinska Clinical Trial Registration (2008) Unique identifier: CT20080014. Registered 04(th) January 2008.

  12. Quantitative microstructural deficits in chronic phase of stroke with small volume infarcts: A diffusion tensor 3-D tractographic analysis.

    PubMed

    Dubey, Prachi; Lioutas, Vasileios-Arsenios; Bhadelia, Rafeeque; Manor, Brad; Novak, Peter; Selim, Magdy; Novak, Vera

    2016-06-01

    Non-infarct zone white matter wallerian degeneration is well-documented in large volume territorial infarctions. However to what extent these abnormalities exist in small volume infarction is not known, particularly since routine T2/FLAIR MR images show minimal changes in such cases. We therefore utilized DTI based quantitative 3D tractography for quantitative assessment of white matter integrity in chronic phase of small volume anterior circulation infarcts. Eleven chronic stroke subjects with small anterior circulation large vessel infarcts (≤10cm(3) volume of primary infarct) were compared with 8 age matched controls. These infarcts had negligible to mild gliosis and encephalomalacia in the primary infarct territory without obvious wallerian degeneration on conventional MRI. Quantitative Diffusion Tensor 3-D tractography was performed for CST, genu and splenium of corpus callosum. Tract based Trace and fractional anisotropy (FA) were compared with age matched controls. On univariate analysis, Chronic stroke subjects had significant elevation in Trace measurement in genu of corpus callosum (GCC), ipsilesional and contralesional CST, (p<0.05), compared to controls. After adjusting for smoking, hypertension (HTN) and non-specific white matter hyperintensities, (WMHs), there was significant elevation in trace within the ipsilesional CST (p=0.05). Contralesional CST FA correlated significantly with walking speed, r=0.67, p=0.03. Stroke subjects with small volume infarcts demonstrate significant quantitative microstructural white matter abnormalities in chronic phase, which are otherwise subthreshold for detection on routine imaging. Ability to quantify these changes provides an important marker for assessing non-infarct zone neuroaxonal integrity in the chronic phase even in the setting of small infarction. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction – MiHeart/AMI study

    PubMed Central

    Dohmann, Hans FR; Silva, Suzana A; Sousa, André LS; Braga, Alcione MS; Branco, Rodrigo VC; Haddad, Andréa F; Oliveira, Mônica A; Moreira, Rodrigo C; Tuche, Fabio AA; Peixoto, Cíntia M; Tura, Bernardo R; Borojevic, Radovan; Ribeiro, Jorge P; Nicolau, José C; Nóbrega, Antonio C; Carvalho, Antonio CC

    2008-01-01

    Background Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls. Methods A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 × 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum). Implications Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required. Trial Register This trial is registered at the NIH registry under the number NCT00350766. PMID:18598362

  14. Chronic intermittent mental stress promotes atherosclerotic plaque vulnerability, myocardial infarction and sudden death in mice.

    PubMed

    Roth, Lynn; Rombouts, Miche; Schrijvers, Dorien M; Lemmens, Katrien; De Keulenaer, Gilles W; Martinet, Wim; De Meyer, Guido R Y

    2015-09-01

    Vulnerable atherosclerotic plaques are prone to plaque rupture leading to acute cardiovascular syndromes and death. Elucidating the risk of plaque rupture is important to define better therapeutic or preventive strategies. In the present study, we investigated the effect of chronic intermittent mental stress on atherosclerotic plaque stability and cardiovascular mortality in apolipoprotein E-deficient (ApoE(-/-)) mice with a heterozygous mutation in the fibrillin-1 gene (Fbn1(C1039G+/)(-)). This mouse model displays exacerbated atherosclerosis with spontaneous plaque ruptures, myocardial infarction and sudden death, when fed a Western-type diet (WD). Female ApoE(-/-)Fbn1(C1039G+/-) mice were fed a WD for up to 25 weeks. After 10 weeks WD, mice were divided in a control (n = 27) and mental stress (n = 29) group. The chronic intermittent mental stress protocol consisted of 3 triggers: water avoidance, damp bedding and restraint stress, in a randomly assigned order lasting 6 h every weekday for 15 weeks. Chronic intermittent mental stress resulted in a significant increase in the amount of macrophages in atherosclerotic plaques of the proximal ascending aorta, whereas type I collagen and fibrous cap thickness were decreased. The coronary arteries of mental stress-treated mice showed larger plaques, more stenosis, and an increased degree of perivascular fibrosis. Moreover, myocardial infarctions occurred more frequently in the mental stress group. As compared to the control group, the survival of stressed ApoE(-/-)Fbn1(C1039G+/-) mice decreased from 67% to 52% at 25 weeks WD, presumably due to myocardial infarctions. In conclusion, chronic intermittent mental stress promotes plaque instability, myocardial infarctions, and mortality of ApoE(-/-)Fbn1(C1039G+/-) mice.

  15. Rotating Frame Spin Lattice Relaxation in a Swine Model of Chronic, Left Ventricular Myocardial Infarction

    PubMed Central

    Witschey, Walter RT; Pilla, James J; Ferrari, Giovanni; Koomalsingh, Kevin; Haris, Mohammed; Hinmon, Robin; Zsido, Gerald; Gorman, Joseph H; Gorman, Robert C; Reddy, Ravinder

    2010-01-01

    T1ρ relaxation times were quantified in a swine model of chronic, left ventricular myocardial infarction. It was found that there were low frequency relaxation mechanisms that suppress endogenous contrast at low spin lock amplitudes and in T2-weighted images. A moderate amplitude spin locking pulse could overcome these relaxation mechanisms. Relaxation dispersion data was measured over a range of RF field amplitudes and a model was formulated to include dipole-dipole relaxation modulated by molecular rotation and an apparent exchange mechanism. These techniques may find some use in the clinic for the observation of chronic, left ventricular cardiac remodeling. PMID:20677236

  16. Improved myocardium transducer

    NASA Technical Reports Server (NTRS)

    Culler, V. H.; Feldstein, C.; Lewis, G. W.

    1979-01-01

    Method of implanting myocardium transducer uses special indented pins that are caught and securely held by epicardial fibers. Pins are small enough to cause minimum of trauma to myocardium during implantation or removal.

  17. p27 kip1 haplo-insufficiency improves cardiac function in early-stages of myocardial infarction by protecting myocardium and increasing angiogenesis by promoting IKK activation.

    PubMed

    Zhou, Ningtian; Fu, Yuxuan; Wang, Yunle; Chen, Pengsheng; Meng, Haoyu; Guo, Shouyu; Zhang, Min; Yang, Zhijian; Ge, Yingbin

    2014-08-07

    p27(kip1) (p27) is widely known as a potent cell cycle inhibitor in several organs, especially in the heart. However, its role has not been fully defined during the early phase of myocardial infarction (MI). In this study, we investigated the relationships between p27, vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) and NF-κB in post-MI cardiac function repair both in vivo and in the hypoxia/ischemia-induced rat myocardiocyte model. In vivo, haplo-insufficiency of p27 improved cardiac function, diminished the infarct zone, protected myocardiocytes and increased angiogenesis by enhancing the production of VEGF/HGF. In vitro, the presence of conditioned medium from hypoxia/ischemia-induced p27 knockdown myocardiocytes reduced the injury caused by hypoxia/ischemia in myocardiocytes, and this effect was reversed by VEGF/HGF neutralizing antibodies, consistent with the cardioprotection being due to VEGF/HGF secretion. We also observed that p27 bound to IKK and that p27 haplo-insufficiency promoted IKK/p65 activation both in vivo and in vitro, thereby inducing the NF-κB downstream regulator, VEGF/HGF. Furthermore, IKKi and IKK inhibitor negated the effect of VEGF/HGF. Therefore, we conclude that p27 haplo-insufficiency protects against heart injury by VEGF/HGF mediated cardioprotection and increased angiogenesis through promoting IKK activation.

  18. Noble gases without anesthetic properties protect myocardium against infarction by activating prosurvival signaling kinases and inhibiting mitochondrial permeability transition in vivo.

    PubMed

    Pagel, Paul S; Krolikowski, John G; Shim, Yon Hee; Venkatapuram, Suneetha; Kersten, Judy R; Weihrauch, Dorothee; Warltier, David C; Pratt, Phillip F

    2007-09-01

    The anesthetic noble gas, xenon, produces cardioprotection. We hypothesized that other noble gases without anesthetic properties [helium (He), neon (Ne), argon (Ar)] also produce cardioprotection, and further hypothesized that this beneficial effect is mediated by activation of prosurvival signaling kinases [including phosphatidylinositol-3-kinase, extracellular signal-regulated kinase, and 70-kDa ribosomal protein s6 kinase] and inhibition of mitochondrial permeability transition pore (mPTP) opening in vivo. Rabbits (n = 98) instrumented for hemodynamic measurement and subjected to a 30-min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion received 0.9% saline (control), three cycles of 70% He-, Ne-, or Ar-30% O2 administered for 5 min interspersed with 5 min of 70% N2-30% O2 before LAD occlusion, or three cycles of brief (5 min) ischemia interspersed with 5 min reperfusion before prolonged LAD occlusion and reperfusion (ischemic preconditioning). Additional groups of rabbits received selective inhibitors of phosphatidylinositol-3-kinase (wortmannin; 0.6 mg/kg), extracellular signal-regulated kinase (PD 098059; 2 mg/kg), or 70-kDa ribosomal protein s6 kinase (rapamycin; 0.25 mg/kg) or mPTP opener atractyloside (5 mg/kg) in the absence or presence of He pretreatment. He, Ne, Ar, and ischemic preconditioning significantly (P < 0.05) reduced myocardial infarct size [23% +/- 4%, 20% +/- 3%, 22% +/- 2%, 17% +/- 3% of the left ventricular area at risk (mean +/- sd); triphenyltetrazolium chloride staining] versus control (45% +/- 5%). Wortmannin, PD 098059, rapamycin, and atractyloside alone did not affect infarct size, but these drugs abolished He-induced cardioprotection. The results indicate that noble gases without anesthetic properties produce cardioprotection by activating prosurvival signaling kinases and inhibiting mPTP opening in rabbits.

  19. Stimulation of glucagon-like peptide-1 receptor through exendin-4 preserves myocardial performance and prevents cardiac remodeling in infarcted myocardium

    PubMed Central

    DeNicola, Megan; Du, Jianfeng; Wang, Zhengke; Yano, Naohiro; Zhang, Ling; Wang, Yigang; Qin, Gangjian; Zhuang, Shougang

    2014-01-01

    We have demonstrated that GLP-1 improved myocardial functional recovery in acute myocardial ischemic injury. However, whether stimulation of the GLP-1 receptor (GLP-1R) with exendin-4, a selective GLP-1R agonist, could initiate a protective effect in the heart remains to be determined. Mouse myocardial infarction (MI) was created by ligation of the left descending artery. After 48 h of MI, animals were divided into the following groups (n = 5–7/group): 1) sham (animals that underwent thoracotomy without ligation), 2) MI [animals that underwent MI and received a daily dose of intraperitoneal injection (ip) of saline]; and 3) MI + exendin-4 [infarcted mice that received injections of exendin-4 (0.1 mg/kg ip)]. Two weeks later, cardiac function was assessed by echocardiography and an isovolumetrically perfused heart. Compared with control MI hearts, stimulation of GLP-1R improved cardiac function, which was associated with attenuation of myocardial hypertrophy, the mitigation of interstitial fibrosis, and an increase in survival rate in post-MI hearts. Furthermore, H9c2 cardiomyoblasts were preconditioned with exendin-4 at a dose of 100 nmol/l and then subjected to hydrogen peroxide exposure at concentrations of 50 and 100 μmol/l. The exendin-4 treatment decreased lactate dehydrogenase leakage and increased cell survival. Notably, this event was also associated with the reduction of cleaved caspase-3 and caspase-9 and attenuation of reactive oxygen species production. Exendin-4 treatments improved mitochondrial respiration and suppressed the opening of mitochondrial permeability transition pore and protected mitochondria function. Our results indicate that GLP-1R serves as a novel approach to eliciting cardioprotection and mitigating oxidative stress-induced injury. PMID:25117407

  20. Proteome changes in the myocardium of experimental chronic diabetes and hypertension: role of PPARα in the associated hypertrophy.

    PubMed

    Ares-Carrasco, S; Picatoste, B; Camafeita, E; Carrasco-Navarro, S; Zubiri, I; Ortiz, A; Egido, J; López, J A; Tuñón, J; Lorenzo, O

    2012-03-16

    Diabetes with or without the presence of hypertension damages the heart. However, there is currently a lack of information about these associated pathologies and the alteration of linked proteins. For these reasons, we were interested in the potential synergistic interaction of diabetes and hypertension in the heart, focusing on the proteome characterization of the pathological phenotypes and the associated hypertrophic response. We treated normotensive and spontaneously hypertensive (SHR) rats with either streptozotocin or vehicle. After 22weeks, type-I diabetic (DM1), SHR, SHR/DM1 and control left-ventricles were studied using proteomic approaches. Proteomics revealed that long-term DM1, SHR and SHR/DM1 rats exhibited 24, 53 and 53 altered proteins in the myocardia, respectively. DM1 myocardium showed over-expression of apoptotic and cytoskeleton proteins, and down-regulation of anti-apoptotic and mitochondrial metabolic enzymes. In both SHR and SHR/DM1 these changes were exacerbated and free fatty-acid (FFA) ß-oxidation enzymes were additionally decreased. Furthermore, SHR/DM1 hearts exhibited a misbalance of specific pro-hypertrophic, anti-apoptotic and mitochondrial ATP-carrier factors, which could cause additional damage. Differential proteins were validated and then clustered into different biological pathways using bioinformatics. These studies suggested the implication of FFA-nuclear receptors and hypertrophic factors in these pathologies. Although key ß-oxidation enzymes were not stimulated in DM1 and hypertensive hearts, peroxisome proliferator-activated receptors-α (PPARα) were potentially activated for other responses. In this regard, PPARα stimulation reduced hypertrophy and pro-hypertrophic factors such as annexin-V in high-glucose and angiotensin-II induced cardiomyocytes. Thus, activation of PPARα could reflect a compensatory response to the metabolic-shifted, apoptotic and hypertrophic status of the hypertensive-diabetic cardiomyopathy.

  1. Induction of a chronic myocardial infarction in the laboratory animal - experimental model

    PubMed Central

    POP, IONEL CIPRIAN; GRAD, NICOLAE-OVIDIU; PESTEAN, COSMIN; TAULESCU, MARIAN; MIRCEAN, MIRCEA; MIRONIUC, ION-AUREL

    2013-01-01

    Introduction Ischemic heart disease is a major public health problem in western countries. Appropriate animal experimental models of chronic myocardial infarction is an essential first step in order to investigate and develop new therapeutic interventions. Aim The aim of this study was to find an optimal place for a coronary artery ligation to induce an optimal chronic myocardial infarction and also a new heart approach that will not require oro-tracheal intubation. Material and methods To achieve these goals we used a group of rabbits and after induction of anesthesia and cardiac exposure by rib osteotomy (rib III, IV and V) at the costo-sternal junction level on the right side we performed three different left anterior descending artery (LAD) ligation at different distances (5, 10 and 15 mm) in relation to the apex. Thirty days after the acute myocardial infarction, we correlated laboratory investigations (serology, ECG, cardiac ultrasound) with histopathological findings. Results Heart approach achieved by rib osteotomy (rib III, IV and V) at the costo-sternal junction level on the right side, maintains the integrity of the ribcage, allowing it to take part in respiratory movements and the animal model does not need oro-tracheal intubation. Ligation of LAD at 15 mm from the apex was incompatible with life; ligation of LAD at 5 mm from the apex does not achieved transmural myocardial infarction and ligation of LAD at 10 mm from the apex achieved a transmural myocardial infarction of the left ventricle which also involved the distal part of the interventricular septum. Conclusion Ligation of LAD at 10 mm from the apex achieved a transmural myocardial infarction of the left ventricle, is in an easily accessible area from technical point of view, it is sufficiently expanded to induce hemodynamic effects that can be quantified with paraclinical examination and also it is compatible with the experimental animal life. If the heart is approached by rib III, IV and V

  2. Tissue extracts from infarcted myocardium of rats in promoting the differentiation of bone marrow stromal cells into cardiomyocyte-like cells.

    PubMed

    Liu, Xiao-Ning; Yin, Qi; Zhang, Hao; Zhang, Hong; Zhu, Shen-Jun; Wei, Ying-Jie; Hu, Sheng-Shou

    2008-04-01

    To investigate whether cardiac tissue extracts from rats could mimic the cardiac microenvironment and act as a natural inducer in promoting the differentiation of bone marrow stromal cells (BMSCs) into cardiomyocytes. Three kinds of tissue extract or cell lysate [infarcted myocardial tissue extract (IMTE), normal myocardial tissue extract (NMTE) and cultured neonatal myocardial lysate (NML)] were employed to induce BMSCs into cardiomyocyte-like cells. The cells were harvested at each time point for reverse transcription-polymerase chain reaction (RT-PCR) detection, immunocytochemical analysis, and transmission electron microscopy. After a 7-day induction, BMSCs were enlarged and polygonal in morphology. Myofilaments, striated sarcomeres, Z-lines, and more mitochondia were observed under transmission electron microscope. Elevated expression levels of cardiac-specific genes and proteins were also confirmed by RT-PCR and immunocytochemistry. Moreover, IMTE showed a greater capacity of differentiating BMSCs into cardiomyocyte-like cells. Cardiac tissue extracts, especially IMTE, can effectively differentiate BMSCs into cardiomyocyte-like cells.

  3. Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca2+ overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats

    PubMed Central

    Liu, Yue-Tao; Zhou, Chao; Jia, Hong-Mei; Chang, Xing; Zou, Zhong-Mei

    2016-01-01

    Xin-Ke-Shu (XKS) is a traditional Chinese patent medicine used for treatment of coronary heart diseases in China. However, its mechanism of action is still unclear. In this paper, the mediation of XKS on the isoproterenol (ISO)-induced myocardial infarction (MI) rat were evaluated based on a tissue-targeted metabonomics in vitro/vivo. The result indicated that twelve metabolic pathways were involved in the therapeutic effect of XKS in vivo, where seven pathways were associated with the Ca2+ overloading mechanism. In agreement with regulation on metabolic variations, XKS markedly reversed the over-expressions of three involved proteins including phospholipase A2 IIA (PLA2 IIA), calcium/calmodulin-dependent protein kinase II (CaMK II) and Pro-Caspase-3. The metabolic regulations of XKS on H9c2 cell also partially confirmed its metabolic effect. These metabolic characteristics in vitro/vivo and western blotting analysis suggested that XKS protected from MI metabolic perturbation major via inhibition of Ca2+ overloading mechanism. Furthermore, 11 active ingredients of XKS exerted steady affinity with the three proteins through the molecular docking study. Our findings indicate that the metabonomics in vitro/vivo combined with western blotting analysis offers the opportunity to gain insight into the comprehensive efficacy of TCMs on the whole metabolic network. PMID:27457884

  4. PATHOLOGICAL EFFECTS OF CHRONIC MYOCARDIAL INFARCTION ON PERIPHERAL NEURONS MEDIATING CARDIAC NEUROTRANSMISSION

    PubMed Central

    Nakamura, Keijiro; Ajijola, Olujimi A.; Aliotta, Eric; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2016-01-01

    Objective To determine whether chronic myocardial infarction (MI) induces structural and neurochemical changes in neurons within afferent and efferent ganglia mediating cardiac neurotransmission. Methods Neuronal somata in i) right atrial (RAGP) and ii) ventral interventricular ganglionated plexi (VIVGP), iii) stellate ganglia (SG) and iv) T1-2 dorsal root ganglia (DRG) bilaterally derived from normal (n = 8) vs. chronic MI (n = 8) porcine subjects were studied. We examined whether the morphology and neuronal nitric oxide synthase (nNOS) expression in soma of RAGP, VIVGP, DRG and SG neurons were altered as a consequence of chronic MI. In DRG, we also examined immunoreactivity of calcitonin gene related peptide (CGRP), a marker of afferent neurons. Results Chronic MI increased neuronal size and nNOS immunoreactivity in VIVGP (but not RAGP), as well as in the SG bilaterally. Across these ganglia, the increase in neuronal size was more pronounced in nNOS immunoreacitive neurons. In the DRG, chronic MI also caused neuronal enlargement, and increased CGRP immunoreactivity. Further, DRG neurons expressing both nNOS and CGRP were increased in MI animals compared to controls, and represented a shift from double negative neurons. Conclusions Chronic MI impacts diverse elements within the peripheral cardiac neuraxis. That chronic MI imposes such widespread, diverse remodeling of the peripheral cardiac neuraxis must be taken into consideration when contemplating neuronal regulation of the ischemic heart. PMID:27209472

  5. Adipose stromal vascular fraction improves cardiac function in chronic myocardial infarction through differentiation and paracrine activity.

    PubMed

    Mazo, Manuel; Cemborain, Arantxa; Gavira, Juan José; Abizanda, Gloria; Araña, Miriam; Casado, Mayte; Soriano, Mario; Hernández, Salomón; Moreno, Cristina; Ecay, Margarita; Albiasu, Edurne; Belzunce, Miriam; Orbe, Josune; Páramo, José Antonio; Merino, Juana; Peñuelas, Iván; Verdugo, José Manuel García; Pelacho, Beatriz; Prosper, Felipe

    2012-01-01

    Fresh adipose-derived cells have been shown to be effective in the treatment of acute myocardial infarction (MI), but their role in the chronic setting is unknown. We sought to determine the long-term effect of the adipose derived-stromal vascular fraction (SVF) cell transplantation in a rat model of chronic MI. MI was induced in 82 rats by permanent coronary artery ligation and 5 weeks later rats were allocated to receive an intramyocardial injection of 10(7) GFP-expressing fresh SVF cells or culture media as control. Heart function and tissue metabolism were determined by echocardiography and (18)F-FDG-microPET, respectively, and histological studies were performed for up to 3 months after transplantation. SVF induced a statistically significant long-lasting (3 months) improvement in cardiac function and tissue metabolism that was associated with increased revascularization and positive heart remodeling, with a significantly smaller infarct size, thicker infarct wall, lower scar fibrosis, and lower cardiac hypertrophy. Importantly, injected cells engrafted and were detected in the treated hearts for at least 3 months, directly contributing to the vasculature and myofibroblasts and at negligible levels to cardiomyocytes. Furthermore, SVF release of angiogenic (VEGF and HGF) and proinflammatory (MCP-1) cytokines, as well as TIMP1 and TIMP4, was demonstrated in vitro and in vivo, strongly suggesting that they have a trophic effect. These results show the potential of SVF to contribute to the regeneration of ischemic tissue and to provide a long-term functional benefit in a rat model of chronic MI, by both direct and indirect mechanisms.

  6. The effect of blockade of the central V1 vasopressin receptors on anhedonia in chronically stressed infarcted and non-infarcted rats.

    PubMed

    Cudnoch-Jedrzejewska, A; Puchalska, L; Szczepanska-Sadowska, E; Wsol, A; Kowalewski, S; Czarzasta, K

    2014-08-01

    Chronic mild stress (CMS) and myocardial infarction (MI) induce anhedonia, which is one of the symptoms of depression. The purpose of this study was to determine the role of the central V1 vasopressin receptors (V1R) in post-CMS and post-MI anhedonia. To this end, we investigated the effect of blockage the central V1R [28days of intracerebroventricular (ICV) infusion of V1 receptors antagonist (V1RANT)] on CMS-induced and the post-infarct anhedonia. The experiments were conducted on conscious MI or sham-operated (SO) rats that were either exposed to CMS for 20days or remained at rest. The sucrose/water intake ratio (S/W) was measured to determine hedonic behavior. Seven days after MI, the S/W was reduced. This effect was no longer present 37days after the infarction and was also absent in the SO rats. Exposure to CMS reduced the S/W in SO rats also. In the CMS-exposed MI rats, the S/W was similar to that in the CMS-exposed SO rats. ICV administration of V1RANT abolished reductions in the S/W in the CMS-exposed MI rats, however, it did not influence S/W in the SO rats exposed to CMS and in the MI and SO rats not exposed to CMS. We conclude that: (1) myocardial infarction and chronic stressing cause anhedonia, (2) myocardial infarction-induced anhedonia appears to be transient, (3) myocardial infarction does not potentiate CMS-induced anhedonia, and (4) CMS-induced anhedonia critically depends on the stimulation of the central V1 receptors.

  7. Chronic administration of an endothelin-A receptor antagonist improves exercise capacity in rats with myocardial infarction-induced congestive heart failure.

    PubMed

    Miyauchi, Takashi; Fujimori, Akira; Maeda, Seiji; Iemitsu, Motoyuki; Sakai, Satoshi; Shikama, Hisataka; Tanabe, Takumi; Matsuda, Mitsuo; Goto, Katsutoshi; Yamaguchi, Iwao

    2004-11-01

    The effects of long-term administration of YM598, a selective endothelin-A antagonist, on improving the exercise tolerance of chronic heart failure model rats were examined using a treadmill exercise loading test. Rats were acclimatized to the treadmill apparatus and the coronary artery was ligated to prepare a myocardial infarction-induced congestive heart failure (CHF) model. Starting 10 days postoperatively, when the acute phase of infarction was over, YM598 was administered orally once daily for approximately 25 weeks at a dose of 1 mg/kg. At weeks 20 and 24 the treadmill test was performed. YM598 prolonged running time, which had been shortened as a result of heart failure. The weights, relative to the body weight, of the left and right ventricles and lungs of surviving rats with CHF were significantly greater than those of sham-operated rats, suggesting hypertrophy of the ventricles and congestion of the lungs. Administration of YM598 markedly reduced ventricular hypertrophy and pulmonary congestion. Examination of cardiac function revealed that, in surviving CHF rats, the peak positive first derivative of left ventricular pressure was significantly lower, and left ventricular end-diastolic pressure, right ventricular systolic pressure and central venous pressure were significantly higher in comparison to sham-operated rats. These data demonstrate that, in rats with CHF, the contractile and diastolic capacity of the left ventricle decreased and pulmonary hypertension and systemic congestion occurred. Long-term administration of YM598 improved left ventricular function of CHF rats to the level of sham-operated rats, and reduced the workload placed on the right side of the heart. Histological examination revealed that long-term treatment with YM598 prevented fibrosis of the surviving left ventricular myocardium. In conclusion, long-term administration of YM598 to rats with CHF improved exercise tolerance and inhibited remodeling of cardiac muscles, leading to

  8. Chronic Myeloid Leukemia: A Case of Extreme Thrombocytosis Causing Syncope and Myocardial Infarction

    PubMed Central

    Ahmed, Brittany; Kadhem, Salam; Truong, Quoc

    2016-01-01

    Chronic myeloid leukemia (CML), a hematologic malignancy characterized by unregulated growth of myelogenous leukocytes, typically presents with symptoms of fatigue, anorexia, and splenomegaly. Laboratory studies often reveal a significant leukocytosis with neutrophilia. A moderate thrombocytosis may be present, but is not usually problematic. The following case discusses a patient who presented with syncope, a convulsive episode, and non ST-segment myocardial infarction secondary to symptomatic thrombocytosis of 2.5 million cells/microL. She was treated with plateletpheresis and subsequently experienced resolution of symptoms. Ultimately, a diagnosis of CML with an atypical presentation of the disease was identified in this patient. PMID:27004153

  9. Creation of Chronic Myocardial Infarction in a Pig (Sus Scrofa) Model

    DTIC Science & Technology

    2015-09-01

    Objectives: The goal of this protocol was to create myocardial infarctions in mini pigs using polystyrenemicrospheres to infarct a portion of the...underwent myocardial infarctions without misadventure. Infusion of polystyrene beads into a diagonal branch of the LAD resulted In a repeatable and...controlled myocardial Infarction.Conclusion: The method reported here provided consistent and repeatable myocardial infarcts with minimal morbidity.

  10. Chronic ischemic mitral regurgitation and papillary muscle infarction detected by late gadolinium-enhanced cardiac magnetic resonance imaging in patients with ST-segment elevation myocardial infarction.

    PubMed

    Bouma, Wobbe; Willemsen, Hendrik M; Lexis, Chris P H; Prakken, Niek H; Lipsic, Erik; van Veldhuisen, Dirk J; Mariani, Massimo A; van der Harst, Pim; van der Horst, Iwan C C

    2016-12-01

    Both papillary muscle infarction (PMI) and chronic ischemic mitral regurgitation (CIMR) are associated with reduced survival after myocardial infarction. The influence of PMI on CIMR and factors influencing both entities are incompletely understood. We sought to determine the influence of PMI on CIMR after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and to define independent predictors of PMI and CIMR. Between January 2011 and May 2013, 263 patients (mean age 57.8 ± 11.5 years) underwent late gadolinium-enhanced cardiac magnetic resonance imaging and transthoracic echocardiography 4 months after PCI for STEMI. Infarct size, PMI, and mitral valve and left ventricular geometric and functional parameters were assessed. Univariate and multivariate analyses were performed to identify predictors of PMI and CIMR (≥grade 2+). PMI was present in 61 patients (23 %) and CIMR was present in 86 patients (33 %). In patients with PMI, 52 % had CIMR, and in patients without PMI, 27 % had CIMR (P < 0.001). In multivariate analyses, infarct size [odds ratio (OR) 1.09 (95 % confidence interval 1.04-1.13), P < 0.001], inferior MI [OR 4.64 (1.04-20.62), P = 0.044], and circumflex infarct-related artery [OR 8.21 (3.80-17.74), P < 0.001] were independent predictors of PMI. Age [OR 1.08 (1.04-1.11), P < 0.001], infarct size [OR 1.09 (1.03-1.16), P = 0.003], tethering height [OR 19.30 (3.28-113.61), P = 0.001], and interpapillary muscle distance [OR 3.32 (1.31-8.42), P = 0.011] were independent predictors of CIMR. The risk of PMI is mainly associated with inferior infarction and infarction in the circumflex coronary artery. Although the prevalence of CIMR is almost doubled in the presence of PMI, PMI is not an independent predictor of CIMR. Tethering height and interpapillary muscle distance are the strongest independent predictors of CIMR.

  11. Paradoxical effects of KB-R7943 on arrhythmogenicity in a chronic myocardial infarction rabbit model.

    PubMed

    Chang, Po-Cheng; Wo, Hung-Ta; Lee, Hui-Ling; Wen, Ming-Shien; Chou, Chung-Chuan

    2015-07-01

    Na(+)/Ca(2+) exchanger blockade has been reported to be anti-arrhythmic in different models. The effects of KB-R7943, a Na(+)/Ca(2+) exchanger blocker, on arrhythmogenesis in hearts with chronic myocardial infarction (MI) remain unclear. Dual voltage and intracellular Ca(2+) (Cai) optical mapping was performed in nine rabbit hearts with chronic MI and four control hearts. Electrophysiology studies including inducibility of ventricular tachyarrhythmias, ventricular fibrillation dominant frequency, action potential, Cai alternans, Cai decay, and conduction velocity were performed. The same protocol was repeated in the presence of KB-R7943 (0.5, 1, and 5μM) after the baseline studies. KB-R7943 was effective in suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias in hearts with chronic MI. Surprisingly, KB-R7943 increased the inducibility of ventricular tachyarrhythmias in a dose-dependent manner (11%, 11%, 22%, and 56% at baseline and with 0.5, 1, and 5μM KB-R7943, respectively, p=0.02). Optical mapping analysis revealed that the underlying mechanisms of the induced ventricular tachyarrhythmias were probably spatially discordant alternans with wave breaks and rotors. Further analysis showed that KB-R7943 significantly enhanced both action potential (p=0.033) and Cai (p=0.001) alternans, prolonged Cai decay (tau value) in a dose-dependent manner (p=0.004), and caused heterogeneous conduction delay especially at peri-infarct zones during rapid burst pacing. In contrast, KB-R7943 had insignificant effects in control hearts. In this chronic MI rabbit model, KB-R7943 has contrasting effects on arrhythmogenesis, suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias, but enhancing the inducibility of tachyarrhythmias. The mechanism is probably the enhanced spatially discordant alternans because of prolonged Cai decay and heterogeneous conduction delay. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier

  12. S100A4 protects the myocardium against ischemic stress.

    PubMed

    Doroudgar, Shirin; Quijada, Pearl; Konstandin, Mathias; Ilves, Kelli; Broughton, Kathleen; Khalafalla, Farid G; Casillas, Alexandria; Nguyen, Kristine; Gude, Natalie; Toko, Haruhiro; Ornelas, Luis; Thuerauf, Donna J; Glembotski, Christopher C; Sussman, Mark A; Völkers, Mirko

    2016-11-01

    Myocardial infarction is followed by cardiac dysfunction, cellular death, and ventricular remodeling, including tissue fibrosis. S100A4 protein plays multiple roles in cellular survival, and tissue fibrosis, but the relative role of the S100A4 in the myocardium after myocardial infarction is unknown. This study aims to investigate the role of S100A4 in myocardial remodeling and cardiac function following infarct damage. S100A4 expression is low in the adult myocardium, but significantly increased following myocardial infarction. Deletion of S100A4 increased cardiac damage after myocardial infarction, whereas cardiac myocyte-specific overexpression of S100A4 protected the infarcted myocardium. Decreased cardiac function in S100A4 Knockout mice was accompanied with increased cardiac remodeling, fibrosis, and diminished capillary density in the remote myocardium. Loss of S100A4 caused increased apoptotic cell death both in vitro and in vivo in part mediated by decreased VEGF expression. Conversely, S100A4 overexpression protected cells against apoptosis in vitro and in vivo. Increased pro-survival AKT-signaling explained reduced apoptosis in S100A4 overexpressing cells. S100A4 expression protects cardiac myocytes against myocardial ischemia and is required for stabilization of cardiac function after MI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Effects of Percutaneous Coronary Intervention on Viable Myocardium and Heart Function of Diabetic Patients With Chronic Total Occlusion.

    PubMed

    Zhou, Guowei; Yang, Wenyi; Li, Liang

    The aim of this study was to compare the effects of percutaneous coronary intervention (PCI) on coronary chronic total occlusion patients with (DM) or without (NDM) diabetes mellitus. A total of 78 patients were divided into DM group and NDM group according to whether the patient has DM. The results of PCI were analyzed using quantitative coronary analysis. In addition, all the patients underwent Tc-MIBI (methoxyisobutylisonitrile) single-photon emission computed tomography (SPECT) and ultrasonic cardiogram in the first week and the sixth month after PCI to evaluate PCI results. During the 6-month follow-up, major adverse cardiac event (MACE) was recorded and analyzed as well. The first and second classes of collateral circulation between the 2 groups have significant differences (P < 0.05). Left ventricular end-diastolic volume index and left ventricular end-systolic volume index were decreased at the sixth month compared with those at the first week. Left ventricular ejection fraction was significantly increased. In both groups, the defect size significantly reduced, and percentage of radionuclide scintigraphic count significantly increased between rest and nitroglycerin interventional SPECT. After 6 months, both groups repeated nitroglycerin interventional SPECT, which showed that defect size was significantly reduced, and the percentage of radionuclide scintigraphic count was significantly increased compared with those of the first week. During the 6-month follow-up, the incidence of MACE between the 2 groups had no significant difference. Percutaneous coronary intervention has beneficial effects on heart functions and MACE when performed on chronic total occlusion patients with and without DM.

  14. Cardiac diffusion-weighted MR imaging in recent, subacute, and chronic myocardial infarction: a pilot study.

    PubMed

    Laissy, Jean-Pierre; Gaxotte, Virginia; Ironde-Laissy, Elisabeth; Klein, Isabelle; Ribet, Aurélie; Bendriss, Ahmed; Chillon, Sylvie; Schouman-Claeys, Elisabeth; Steg, P Gabriel; Serfaty, Jean-Michel

    2013-12-01

    To investigate the clinical feasibility of diffusion-weighted imaging (DWI) to detect recent myocardial infarction (MI) and to differentiate it from subacute and chronic MI, with late-gadolinium enhancement (LGE) sequence as reference. Furthermore, to measure variation of the myocardial apparent diffusion coefficient (ADC) according to the age of MI. Seventy-four MI patients were separated in 3 groups. Group A included 34 recent (< 8 days) MI patients; group B, 22 subacute (9-90 days) MI patients; group C, 18 chronic (> 90 days) MI patients; a fourth group (group D) included 24 controls. DWI and LGE images were acquired on a 1.5T system. DWI and LGE matched images were assessed visually by two blinded observers for hyperintense areas in corresponding segments. Qualitative assessment of DWI compared with LGE images yielded a sensitivity of 97% and a specificity of 61%/14% to differentiate recent from chronic/subacute MI, respectively. The absolute ADCs (recent 0.00632 ± 0.00037 mm(2) /s, subacute 0.00639 ± 0.00035 mm(2) /s, chronic 0.00743 ± 0.00056 mm(2) /s, remote or normal 0.00895 ± 0.00019 mm(2) /s) and relative ADCs were significantly different between groups (P < 0.001) except between recent and subacute MIs. DWI is a sensitive technique to diagnose recent MI. DWI MR sequences could help differentiate recent from chronic MI. From these preliminary results, one should expect DWI to be used in the triage of emergency patients with atypical chest pain, to clarify if an MI is present or not in just a few minutes. Copyright © 2013 Wiley Periodicals, Inc.

  15. Post myocardial infarction of the left ventricle: the course ahead seen by cardiac MRI

    PubMed Central

    Masci, Pier Giorgio

    2012-01-01

    In the last decades, cardiac magnetic resonance imaging (MRI) has gained acceptance in cardiology community as an accurate and reproducible diagnostic imaging modality in patients with ischemic heart disease (IHD). In particular, in patients with acute myocardial infarction (MI) cardiac MRI study allows a comprehensive assessment of the pattern of ischemic injury in term of reversible and irreversible damage, myocardial hemorrhage and microvascular obstruction (MVO). Myocardial salvage index, derived by quantification of myocardium (area) at risk and infarction, has become a promising surrogate end-point increasingly used in clinical trials testing novel or adjunctive reperfusion strategies. Early post-infarction, the accurate and reproducible quantification of myocardial necrosis, along with the characterization of ischemic myocardial damage in its diverse components, provides important information to predict post-infarction left ventricular (LV) remodeling, being useful for patients stratification and management. Considering its non-invasive nature, cardiac MRI suits well for investigating the time course of infarct healing and the changes occurring in peri-infarcted (adjacent) and remote myocardium, which ultimately promote the geometrical, morphological and functional abnormalities of the entire left ventricle (global LV remodeling). The current review will focus on the cardiac MRI utility for a comprehensive evaluation of patients with acute and chronic IHD with particular regard to post-infarction remodeling. PMID:24282705

  16. In vivo amino acid transport of subacute and chronic cerebral infarction evaluated by 12-18F-phenylalanine

    SciTech Connect

    Shimosegawa, E.; Miura, S.; Murakami, M.

    1994-05-01

    On the basis of previous validation of kinetic two-compartment model and the determination of normal values of three parameters (k{sub 1}:influx rate constant, k{sub 2}:outflux rate constant, Vd:distribution volume), PET measurements of in vivo amino acid transport from blood to brain using L-(2-18F)-fluorophenylalanine ({sup 18}F-Phe) were undergone in the patients with cerebral infarction. The purposes of this study are to evaluate the alteration of amino acid transport in subacute and chronic stage of cerebral infarction and to compare with cerebral blood flow (CBF) and oxygen metabolism. Dynamic {sup 18}F-Phe PET studies for 50 minutes were performed in 7 patients with cerebral infarction. The input function was obtained by 27 points of arterial sampling. In all patients, measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO{sub 2}), and oxygen extraction fraction (OEF) were made on the same day of {sup 18}F-Phe PET measurement. Each patient was studied twice, within 2 weeks of the onset and 3 months later. Weighted integration technique with table look-up method was applied for the reconstruction of parametric images of {sup 18}F-Phe and ROI analysis of k{sub 1}, k{sub 2}, and Vd. In subacute stage, significant reduction of k{sub 2} value in infarct area was observed when compared to that in periinfarct area (p<0.05) and in normal cortices (p<0.001). k{sub 1} value in this stage showed only slightly decrease in infarct area, therefore, Vd value in infarct area increased significantly compared to normal cortices (p<0.001). In chronic stage, both k{sub 1} and k{sub 2} values in infarct area were significantly lower than that in normal cortices (p<0.001), and corresponding Vd value reduced to normal level. Correlativity between kinetic parameters of {sup 18}F-Phe and CBF or oxygen metabolism was not observed both in subacute and chronic stage of infarction.

  17. Deadly association of cardiogenic shock and chronic total occlusion in acute ST-elevation myocardial infarction.

    PubMed

    Bataille, Yoann; Déry, Jean-Pierre; Larose, Éric; Déry, Ugo; Costerousse, Olivier; Rodés-Cabau, Josep; Gleeton, Onil; Proulx, Guy; Abdelaal, Eltigani; Machaalany, Jimmy; Nguyen, Can M; Noël, Bernard; Bertrand, Olivier F

    2012-10-01

    The association between cardiogenic shock and 1 or >1 chronic total occlusion (CTO) in unselected patients presenting with ST-elevation myocardial infarction (MI) (STEMI) has not been characterized. Patients with STEMI referred with or without cardiogenic shock were categorized into no CTO, 1 CTO, and >1 CTO. The primary end point was the 30-day mortality. Between 2006 and 2011, 2,020 consecutive patients were included. A total of 141 patients (7%) presented with cardiogenic shock on admission. The prevalence of 1 CTO and >1 CTO in a non-infarct-related artery was 23% and 5%, respectively, among patients with shock compared with 6% and 0.5% in patients without shock (P < .0001). Independent predictors of cardiogenic shock included left main-related MI (odds ratio [OR] 6.55, 95% CI 1.39-26.82, P = .019), CTO (OR 4.20, 95% CI 2.64-6.57, P < .001), creatinine clearance <60 mL/min (OR 3.41, 95% CI 2.32-4.99, P < .0001), and left anterior descending-related MI (OR 2.20, 95% CI 1.51-3.23, P < .0001). Thirty-day mortality was 100% in shock patients with >1 CTO, 65.6% with 1 CTO, and 40.2% in patients without CTO (P < .0001). After adjustment for left ventricular ejection fraction and renal function, CTO remained an independent predictor for 30-day mortality (hazard ratio [HR] 1.83; 95% CI 1.10-3.01, P = .02). In patients with STEMI, CTO was strongly associated with cardiogenic shock on admission. In this setting, mortality was substantially higher in patients with 1 CTO and exceedingly high in those with >1 CTO. The presence of CTO was an independent predictor of early mortality. Copyright © 2012 Mosby, Inc. All rights reserved.

  18. Gene transfer of hepatocyte growth factor gene improves learning and memory in the chronic stage of cerebral infarction.

    PubMed

    Shimamura, Munehisa; Sato, Naoyuki; Waguri, Satoshi; Uchiyama, Yasuo; Hayashi, Takuya; Iida, Hidehiro; Nakamura, Toshikazu; Ogihara, Toshio; Kaneda, Yasufumi; Morishita, Ryuichi

    2006-04-01

    There is no specific treatment to improve the functional recovery in the chronic stage of ischemic stroke. To provide the new therapeutic options, we examined the effect of overexpression of hepatocyte growth factor (HGF) in the chronic stage of cerebral infarction by transferring the HGF gene into the brain using hemagglutinating virus of Japan envelope vector. Sixty rats were exposed to permanent middle cerebral artery occlusion (day 1). Based on the sensorimotor deficits at day 7, the rats were divided equally into control vector or HGF-treated rats. At day 56, rats transfected with the HGF gene showed a significant recovery of learning and memory in Morris water maze tests (control vector 50+/-4 s; HGF 33+/-5 s; P<0.05) and passive avoidance task (control vector 132.4+/-37.5 s; HGF 214.8+/-26.5 s; P<0.05). Although the total volume of cerebral infarction was not related to the outcome, immunohistochemical analysis for Cdc42 and synaptophysin in the peri-infarct region revealed that HGF enhanced the neurite extension and increased synapses. Immunohistochemistry for glial fibriary acidic protein revealed that the formation of glial scar was also prevented by HGF gene treatment. Additionally, the number of the arteries was increased in the HGF group at day 56. These data demonstrated that HGF has a pivotal role for the functional recovery after cerebral infarction through neuritogenesis, improved microcirculation, and the prevention of gliosis. Our results also provide evidence for the feasibility of gene therapy in the chronic stage of cerebral infarction.

  19. Prevalence and prognosis of unrecognized myocardial infarctions in chronic kidney disease

    PubMed Central

    Rizk, Dana V.; Gutierrez, Orlando; Levitan, Emily B.; McClellan, William M.; Safford, Monika; Soliman, Elsayed Z.; Warnock, David G.; Muntner, Paul

    2012-01-01

    Background Unrecognized myocardial infarctions (UMIs) are common in the general population but have not been well studied in patients with chronic kidney disease (CKD). The purpose of this study was to determine the prevalence and prognosis for mortality of UMI among adults with CKD. Methods The current study included 18 864 participants in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study who completed a baseline examination including a 12-lead electrocardiogram (ECG). UMI was defined as the presence of myocardial infarction (MI) by Minnesota ECG classification in the absence of self-reported or recognized MI (RMI). Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and albuminuria using albumin-to-creatinine ratio from a spot urine sample. All-cause mortality was assessed over a median 4 years of follow-up. Results The prevalence of UMI was 4, 6, 6 and 13% among participants with eGFR levels of ≥60, 45–59.9, 30–44.9 and <30 mL/min/1.73m2, respectively, and 4, 5, 7 and 10% among participants with albuminuria levels of <10, 10–29.9, 30–299.9 and ≥300 mg/g, respectively. Compared to those with no MI, the multivariable adjusted hazard ratio for all-cause mortality associated with UMI and RMI was 1.65 [95% confidence interval (CI): 1.09–2.49] and 1.65 (95% CI: 1.20–2.26), respectively, among individuals with an eGFR <60 mL/min/1.73m2 and 1.49 (95% CI: 1.03–2.16) and 1.88 (95% CI: 1.40–2.52) among individuals with albuminuria ≥30 mg/g. Conclusion UMIs are common among individuals with an eGFR <60 mL/min/1.73m2 and albuminuria and associated with an increased mortality risk. PMID:22167594

  20. PROTECTIVE EFFECT OF Ailanthus excelsa ROXB IN MYOCARDIAL INFARCTION POST MESENCHYMAL STEM CELL TRANSPLANTATION: STUDY IN CHRONIC ISCHEMIC RAT MODEL

    PubMed Central

    Gong, Xia

    2016-01-01

    Background: Thia study evaluates the effects of Ailanthus excelsa Roxb methanolic extract (AER-ME) in rats induced with Myocardial Infarction (MI) followed by transplantation of MSCs. Material and Methods: Rats were induced with MI by ligation technique of left coronary artery. The sham-operated the control and AER-ME treated group of rats received transplantation of PKH-26 and marked MSCs followed by normal saline and AER-ME treatment (200mg/kg/day of AER-ME extract) respectively for 30 days. Parameters such as cardiac function, inflammation, oxidative stress, apoptosis and differentiation of MSCs (angiogenesis) were evaluated. Histological studies of infracted myocardium reveled anti-inflammatory activity of AER-ME treatment. Result and Discussion: Oxidative stress parameters revealed decrease in levels of malondialdehyde (MDA) and increase in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHpx) activity significantly indicating antioxidant activity of the extract. There was a reduction in cell death rate of treated rats due to the decrease in apoptotic index with prolongation of MI when compared to both control and sham-operated groups. The expression of Fas protein was parallel to apoptotic index. The vascular density increased significantly in extract treated group. The treatment showed improved cardiac activity with decreased left ventricular end diastolic (LVEDP) and arterial pressure while the left ventricular end systolic pressure (LVEP) and dp/dtmax increased significantly when compared to both control and sham-operated groups respectively showing the protective effect of the extract as necessitated by the transplantation of MSCs. The study marked the protective outcomes of AER-ME treatment for MSCs in microenvironment of infracted myocardium by improving their viability and increasing differentiation into cardiomyocytes. PMID:28480373

  1. PROTECTIVE EFFECT OF Ailanthus excelsa ROXB IN MYOCARDIAL INFARCTION POST MESENCHYMAL STEM CELL TRANSPLANTATION: STUDY IN CHRONIC ISCHEMIC RAT MODEL.

    PubMed

    Gong, Xia

    2016-01-01

    Thia study evaluates the effects of Ailanthus excelsa Roxb methanolic extract (AER-ME) in rats induced with Myocardial Infarction (MI) followed by transplantation of MSCs. Rats were induced with MI by ligation technique of left coronary artery. The sham-operated the control and AER-ME treated group of rats received transplantation of PKH-26 and marked MSCs followed by normal saline and AER-ME treatment (200mg/kg/day of AER-ME extract) respectively for 30 days. Parameters such as cardiac function, inflammation, oxidative stress, apoptosis and differentiation of MSCs (angiogenesis) were evaluated. Histological studies of infracted myocardium reveled anti-inflammatory activity of AER-ME treatment. Oxidative stress parameters revealed decrease in levels of malondialdehyde (MDA) and increase in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHpx) activity significantly indicating antioxidant activity of the extract. There was a reduction in cell death rate of treated rats due to the decrease in apoptotic index with prolongation of MI when compared to both control and sham-operated groups. The expression of Fas protein was parallel to apoptotic index. The vascular density increased significantly in extract treated group. The treatment showed improved cardiac activity with decreased left ventricular end diastolic (LVEDP) and arterial pressure while the left ventricular end systolic pressure (LVEP) and dp/dtmax increased significantly when compared to both control and sham-operated groups respectively showing the protective effect of the extract as necessitated by the transplantation of MSCs. The study marked the protective outcomes of AER-ME treatment for MSCs in microenvironment of infracted myocardium by improving their viability and increasing differentiation into cardiomyocytes.

  2. Acute Infarct Extracellular Volume Mapping to Quantify Myocardial Area at Risk and Chronic Infarct Size on Cardiovascular Magnetic Resonance Imaging.

    PubMed

    Garg, Pankaj; Broadbent, David A; Swoboda, Peter P; Foley, James R J; Fent, Graham J; Musa, Tarique A; Ripley, David P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Haaf, Philip; Kidambi, Ananth; van der Geest, Rob J; Greenwood, John P; Plein, Sven

    2017-07-01

    Late gadolinium enhancement (LGE) imaging overestimates acute infarct size. The main aim of this study was to investigate whether acute extracellular volume (ECV) maps can reliably quantify myocardial area at risk (AAR) and final infarct size (IS). Fifty patients underwent cardiovascular magnetic resonance imaging acutely (24-72 hours) and at convalescence (3 months). The cardiovascular magnetic resonance protocol included cines, T2-weighted imaging, native T1 maps, 15-minute post-contrast T1 maps, and LGE. Optimal AAR and IS ECV thresholds were derived in a validation group of 10 cases (160 segments). Eight hundred segments (16 per patient) were analyzed to quantify AAR/IS by ECV maps (ECV thresholds for AAR is 33% and IS is 46%), T2-weighted imaging, T1 maps, and acute LGE. Follow-up LGE imaging was used as the reference standard for final IS and viability assessment. The AAR derived from ECV maps (threshold of >33) demonstrated good agreement with T2-weighted imaging-derived AAR (bias, 0.18; 95% confidence interval [CI], -1.6 to 1.3) and AAR derived from native T1 maps (bias=1; 95% CI, -0.37 to 2.4). ECV demonstrated the best linear correlation to final IS at a threshold of >46% (R=0.96; 95% CI, 0.92-0.98; P<0.0001). ECV maps demonstrated better agreement with final IS than acute IS on LGE (ECV maps: bias, 1.9; 95% CI, 0.4-3.4 versus LGE imaging: bias, 10; 95% CI, 7.7-12.4). On multiple variable regression analysis, the number of nonviable segments was independently associated with IS by ECV maps (β=0.86; P<0.0001). ECV maps can reliably quantify AAR and final IS in reperfused acute myocardial infarction. Acute ECV maps were superior to acute LGE in terms of agreement with final IS. IS quantified by ECV maps are independently associated with viability at follow-up. © 2017 American Heart Association, Inc.

  3. Comparison of chronic kidney disease and risk for presenting with painless versus nonpainless acute myocardial infarction.

    PubMed

    Lee, Min Goo; Jeong, Myung Ho; Lee, Ki Hong; Park, Keun Ho; Sim, Doo Sun; Yoon, Hyun Ju; Yoon, Nam Sik; Kim, Kye Hun; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

    2012-09-15

    Chronic kidney disease increases the risk for developing ischemic heart disease, but it has not been well known whether it also affects the manifestation of painless acute myocardial infarction (AMI), which has important clinical implications. The aim of this study was to identify whether chronic kidney disease is associated with the presentation of painless AMI. A total of 2,656 consecutively hospitalized patients with AMI from January 2008 to February 2012 were enrolled. Estimated glomerular filtration rate (eGFR) was calculated using calibrated serum creatinine and the abbreviated Modification of Diet in Renal Disease (MDRD) equation. Patient clinical characteristics, angiographic findings, and the use of medications were reviewed. Multivariate logistic regression analysis was used to examine the association of reduced eGFR and presentation with painless AMI. A total of 2,176 adults with painful AMI and 480 adults with painless AMI were studied, and baseline eGFR was calculated. Mean eGFR was lower in subjects with painless AMI compared to those with painful AMI. Compared to an eGFR >90 ml/min/1.73 m(2), a strong, graded, independent association was observed between reduced eGFR and presentation with painless AMI, with adjusted odds ratios of 1.65 (95% confidence interval 1.16 to 2.36) for an eGFR of 60 to 89 ml/min/1.73 m(2), 2.92 (95% confidence interval 1.89 to 4.52) for an eGFR of 45 to 59 ml/min/1.73 m(2), and 3.44 (95% confidence interval 2.20 to 5.38) for an eGFR <45 ml/min/1.73 m(2). In conclusion, lower eGFR was a strong, independent predictor of presentation with painless AMI versus painful AMI.

  4. Lipoprotein(a) and Risk of Myocardial Infarction and Death in Chronic Kidney Disease: Findings From the CRIC Study (Chronic Renal Insufficiency Cohort).

    PubMed

    Bajaj, Archna; Damrauer, Scott M; Anderson, Amanda H; Xie, Dawei; Budoff, Matthew J; Go, Alan S; He, Jiang; Lash, James P; Ojo, Akinlolu; Post, Wendy S; Rahman, Mahboob; Reilly, Muredach P; Saleheen, Danish; Townsend, Raymond R; Chen, Jinbo; Rader, Daniel J

    2017-10-01

    To investigate the effect of LPA gene variants and renal function on lipoprotein(a) [Lp(a)] levels in people with chronic kidney disease and determine the association between elevated Lp(a) and myocardial infarction and death in this setting. The CRIC Study (Chronic Renal Insufficiency Cohort) is an ongoing prospective study of 3939 participants with chronic kidney disease. In 3635 CRIC participants with genotype data, carriers of the rs10455872 or rs6930542 variants had a higher median Lp(a) level (mg/dL) compared with noncarriers (73 versus 23; P<0.001 and 56 versus 22; P<0.001, respectively). The 3744 participants (55% male and 41% non-Hispanic White) with available baseline Lp(a) levels were stratified into quartiles of baseline Lp(a) (mg/dL): <9.8, 9.8 to 26.0, 26.1 to 61.3, and >61.3. There were 315 myocardial infarctions and 822 deaths during a median follow-up of 7.5 years. The second quartile had the lowest event rate. After adjusting for potential confounders and using a Cox proportional hazards model, the highest quartile of Lp(a) was associated with increased risk of myocardial infarction (hazard ratio, 1.49; 95% confidence interval, 1.05-2.11), death (hazard ratio, 1.28; 95% confidence interval, 1.05-1.57), and the composite outcome (hazard ratio, 1.29; 95% confidence interval, 1.07-1.56) compared with the second quartile of Lp(a). Among adults with chronic kidney disease, elevated Lp(a) is independently associated with myocardial infarction and death. Future studies exploring pharmacological Lp(a) reduction in this population are warranted. © 2017 American Heart Association, Inc.

  5. Prevalence, predictors and clinical impact of unique and multiple chronic total occlusion in non-infarct-related artery in patients presenting with ST-elevation myocardial infarction.

    PubMed

    Bataille, Yoann; Déry, Jean-Pierre; Larose, Eric; Déry, Ugo; Costerousse, Olivier; Rodés-Cabau, Josep; Rinfret, Stéphane; De Larochellière, Robert; Abdelaal, Eltigani; Machaalany, Jimmy; Barbeau, Gérald; Roy, Louis; Bertrand, Olivier F

    2012-12-01

    To investigate the predictors and impact on long-term survival of one chronic total occlusion (CTO) or multiple CTOs in patients presenting with ST-elevation myocardial infarction (STEMI). Single-centre retrospective observational study. University-based tertiary referral centre. Between 2006 and 2011, a total of 2020 consecutive patients referred with STEMI were categorised into single vessel disease, multivessel disease (MVD) without CTO, with one CTO or with multiple CTOs. Primary percutaneous coronary intervention. The primary end-point was the 1-year mortality. The prevalence of single vessel disease, MVD without CTO, with one CTO or with multiple CTOs was 70%, 22%, 7.2% and 0.8%, respectively. Independent clinical predictors for the presence of CTO were cardiogenic shock (OR 5.05; 95% CI 3.29 to 7.64), prior myocardial infarction (OR 2.06; 95% CI 1.35 to 3.09), age >65 years (OR 1.94; 95% CI 1.40 to 2.71) and history of angina (OR 1.94; 95% CI 1.29 to 2.87). Mortality was worse in patients with multiple CTOs (76.5%) compared with those with one CTO (28.1%) or without CTO (7.3%) (p<0.0001). After adjustment for left ventricular ejection fraction and renal function, MVD was an independent predictor for 1-year mortality (HR: 1.81; 95% CI 1.18 to 2.77, p=0.007), but CTO was not (HR: 1.07; 95% CI 0.66 to 1.73, p=0.78). Simple clinical factors are associated with the presence of CTO in non-infarct-related artery in patients presenting with STEMI. In these patients, long-term survival was independently associated with MVD, left ventricular ejection fraction and renal function, but not with CTO per se.

  6. Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia.

    PubMed

    Maslov, Leonid N; Naryzhnaia, Natalia V; Tsibulnikov, Sergey Yu; Kolar, Frantisek; Zhang, Yi; Wang, Hongxin; Gusakova, Anna M; Lishmanov, Yury B

    2013-09-17

    The objective of this study was to examine the involvement of endogenous opioid peptides and opioid receptor (OR) subtypes in the cardioprotective effect of adaptation to chronic hypoxia in rats. Rats were exposed to continuous normobaric hypoxia (CNH; 12% oxygen) for 3 weeks. Myocardial ischemia was induced by 20-min coronary artery occlusion followed by 3-h reperfusion in anesthetized open-chest animals. Various OR antagonists were administered to rats prior to ischemia. The size of myocardial infarction and the incidence of ischemic ventricular arrhythmias were assessed. Myocardial and plasma concentrations of opioid peptides (met-enkephalin, β-endorphin, and endomorphins) were determined. Adaptation to CNH significantly increased myocardial and plasma concentrations of opioids, potentiated their further elevation by ischemia/reperfusion, and reduced myocardial infarct size, but it did not affect the incidence of ischemic arrhythmias. The infarct size-limiting effect of CNH was abolished by OR antagonists naltrexone (non-selective), naloxone methiodide (non-selective peripherally acting), TIPP[ψ] (δ-OR), naltriben (δ2-OR), or CTAP (μ-OR), while BNTX (δ1-OR) and nor-binaltorphimine (κ-OR) had no effect. The results suggest that the infarct size-limiting effect afforded by adaptation to CNH is mediated by activation of peripheral δ2- and μ-ORs by elevated levels of endogenous opioid peptides. © 2013.

  7. Impact of Percutaneous Coronary Intervention for Chronic Total Occlusion in Non-Infarct-Related Arteries in Patients With Acute Myocardial Infarction (from the COREA-AMI Registry).

    PubMed

    Choi, Ik Jun; Koh, Yoon-Seok; Lim, Sungmin; Choo, Eun Ho; Kim, Jin Jin; Hwang, Byung-Hee; Kim, Tae-Hoon; Seo, Suk Min; Kim, Chan Joon; Park, Mahn-Won; Shin, Dong Il; Choi, Yun-Seok; Park, Hun-Jun; Her, Sung-Ho; Kim, Dong-Bin; Park, Chul Soo; Lee, Jong-Min; Moon, Keon Woong; Chang, Kiyuk; Kim, Hee Yeol; Yoo, Ki-Dong; Jeon, Doo Soo; Chung, Wook-Sung; Ahn, Youngkeun; Jeong, Myung Ho; Seung, Ki-Bae; Kim, Pum-Joon

    2016-04-01

    Chronic total occlusion (CTO) in a non-infarct-related artery (IRA) is an independent predictor of clinical outcomes in patients with acute myocardial infarction (AMI). This study evaluated the impact of successful percutaneous coronary intervention (PCI) for CTO of a non-IRA on the long-term clinical outcomes in patients with AMI. A total of 4,748 patients with AMI were consecutively enrolled in the Convergent Registry of Catholic and Chonnam University for AMI registry from January 2004 to December 2009. We enrolled 324 patients with CTO in a non-IRA. To adjust for baseline differences, propensity matching (96 matched pairs) was used to compare successful PCI and occluded CTO for the treatment of CTO in non-IRA. The primary clinical end points were all-cause mortality and a composite of the major adverse cardiac events, including cardiac death, MI, stroke, and any revascularization during the 5-year follow-up. Patients who received successful PCI for CTO of non-IRA had lower rates of all-cause mortality (16.7% vs 32.3%, hazard ratio 0.459, 95% CI 0.251 to 0.841, p = 0.012) and major adverse cardiac events (21.9% vs 55.2%, hazard ratio 0.311, 95% CI 0.187 to 0.516, p <0.001) compared with occluded CTO group. Subgroup analyses revealed that successful PCI resulted in a better mortality rate in patients with normal renal function compared to patients with chronic kidney disease (p = 0.010). In conclusion, successful PCI for CTO of non-IRA is associated with improved long-term clinical outcomes in patients with AMI.

  8. The Excitatory Synaptic Transmission of the Nucleus of Solitary Tract Was Potentiated by Chronic Myocardial Infarction in Rats

    PubMed Central

    Feng, Ban; Zhang, Zi-Nan; Lei, Jie; Li, Yun-Qing; Du, Jian-Qing; Chen, Tao

    2015-01-01

    Angina pectoris is a common clinical symptom that often results from myocardial infarction. One typical characteristic of angina pectoris is that the pain does not match the severity of the myocardial ischemia. One possible explanation is that the intensity of cardiac nociceptive information could be dynamically regulated by certain brain areas. As an important nucleus for processing cardiac nociception, the nucleus of the solitary tract (NTS) has been studied to some extent. However, until now, the morphological and functional involvement of the NTS in chronic myocardial infarction (CMI) has remained unknown. In the present study, by exploring left anterior descending coronary artery ligation surgery, we found that the number of synaptophysin-immunoreactive puncta and Fos-immunoreactive neurons in the rat NTS two weeks after ligation surgery increased significantly. Excitatory pre- and postsynaptic transmission was potentiated. A bath application of a Ca2+ channel inhibitor GABApentin and Ca2+ permeable AMPA receptor antagonist NASPM could reverse the potentiated pre- and postsynaptic transmission, respectively. Meanwhile, rats with CMI showed significantly increased visceral pain behaviors. Microinjection of GABApentin or NASPM into the NTS decreased the CMI-induced visceral pain behaviors. In sum, our results suggest that the NTS is an important area for the process of cardiac afference in chronic myocardial infarction condition. PMID:25756354

  9. Cellular cardiomyoplasty: a new therapeutic approach for regenerating the myocardium.

    PubMed

    Piano, Mariann R; Carrigan, Timothy M

    2003-01-01

    One of the most promising new therapeutic techniques for the augmentation and regeneration of the myocardium is cellular cardiomyoplasty. Reports from animal and clinical investigations indicate that the transplant of different cell types, such as autologous skeletal myoblasts and adult stem cells, into injured myocardium results in the generation of new cardiac myocytes and improvement in myocardial performance. Although there is no consensus with regard to the best cell type to transplant or the extent of myocardial renewal and regeneration, the technique of cardiac cellular myoplasty may become one of the most important advancements in the treatment of cardiovascular diseases such as myocardial infarction and heart failure.

  10. System of scale-selective tomography of myocardium birefringence

    NASA Astrophysics Data System (ADS)

    Ushenko, O. G.; Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Ushenko, Yu. O.; Dubolazov, O. V.; Savich, V. O.

    2015-09-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  11. Impact of acute and chronic hyperglycemia on in-hospital outcomes of patients with acute myocardial infarction.

    PubMed

    Fujino, Masashi; Ishihara, Masaharu; Honda, Satoshi; Kawakami, Shoji; Yamane, Takafumi; Nagai, Toshiyuki; Nakao, Kazuhiro; Kanaya, Tomoaki; Kumasaka, Leon; Asaumi, Yasuhide; Arakawa, Tetsuo; Tahara, Yoshio; Nakanishi, Michio; Noguchi, Teruo; Kusano, Kengo; Anzai, Toshihisa; Goto, Yoichi; Yasuda, Satoshi; Ogawa, Hisao

    2014-12-15

    This study was undertaken to assess the impact of acute hyperglycemia (acute-HG) and chronic hyperglycemia (chronic-HG) on short-term outcomes in patients with acute myocardial infarction (AMI). This study consisted of 696 patients with AMI. Acute-HG was defined as admission plasma glucose ≥200 mg/dl and chronic-HG as hemoglobin A1c ≥6.5%. Acute-HG was associated with higher peak serum creatine kinase (4,094 ± 4,594 vs 2,526 ± 2,227 IU/L, p <0.001) and in-hospital mortality (9.8% vs 1.6%, p <0.001). On the contrary, there was no significant difference in peak creatine kinase (2,803 ± 2,661 vs 2,940 ± 3,181 IU/L, p = 0.59) and mortality (3.3 vs 3.7%, p = 0.79) between patients with chronic-HG and those without. Multivariate analysis showed that admission plasma glucose was an independent predictor of in-hospital mortality (odds ratio 1.15, 95% confidence interval 1.05 to 1.27, p <0.001), but hemoglobin A1c was not. When only patients with acute-HG were analyzed, chronic-HG was associated with a significantly smaller infarct size (3,221 ± 3,001 vs 5,904 ± 6,473 IU/L, p <0.001) and lower in-hospital mortality (5.5 vs 18.9%, p = 0.01). In conclusion, these results suggested that acute-HG, but not chronic-HG, was associated with adverse short-term outcomes after AMI. Paradoxically, in patients with acute-HG, chronic-HG might abate the adverse effects of acute-HG.

  12. Non-Q-wave myocardial infarction: comprehensive analysis of electrocardiogram, pathophysiology, and therapeutics.

    PubMed

    Velasco, Manuel; Rojas, Edward

    2013-01-01

    Since the invention of electrocardiogram (ECG or EKG), its significance in the diagnosis of acute ischemic disease, chronic ischemic disease, and its contribution to cardiology has been no less than remarkable. The pathophysiology of acute coronary syndromes in most cases correlates with the clinical outcomes, biochemical findings (cardiac biomarkers), and electrocardiographic patterns. Electric activity in the myocardium is registered in the ECG describing positive deflections when the depolarization potential orientates positive charges to the recording electrode (approaches to it) and negative deflections when the depolarization potential orientates negative charges to the recording electrode and gets away from it. The abnormal Q-wave is the cornerstone of the myocardial infarction diagnosis after several days of the ischemic event. Findings in the ECG suggestive of ischemia and necrosis are ST elevation/depression and deep Q-waves, respectively, and the presence of a deep abnormal Q-wave in the ECG is evidence of necrotic areas and an inert myocardium, which is not capable to depolarize. Non-Q-wave myocardial infarction has been defined as acute myocardial infarction without a new-onset deep Q-wave on the ECG after day(s) of evolution, and because of the anatomopathological concept of infarction is usually related to necrosis, it results paradoxical to consider this widely known clinical and biochemical entity as a myocardial infarction when there is no evidence of necrosis in the ECG.

  13. Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution.

    PubMed Central

    Fishbein, M. C.; Maclean, D.; Maroko, P. R.

    1978-01-01

    Surgical occlusion of the left coronary artery of the rat is a relatively simple, economical technique for producing experimental myocardial infarction (MI). Histologic study of 1- to 21-day-old MI in rats showed that following a mild and brief acute inflammatory response at the margins of the necrotic myocardium, there is chronic inflammation, vascular and collagenous proliferation, and resorption of necrostic tissue which progresses until scar formation is complete, usually by 21 days. From Day 1 to Day 21 the volume of infarcted myocardium decreases from 45.9 +/- 5.9% (mean +/- SEM) to 26.1 +/- 3.2% of the left ventricle and infarct thickness decreases from 1.30 +/- 0.06 mm to 0.47 +/- 0.02 mm. Concomitantly, the percent of the surface area of the left ventricle which is infarcted decreases insignificantly from 55.7 +/- 7.2% to 48.3 +/- 4.2%, indicating that the decrease in volume of the infarcted tissue occurs primarily as a result of thinning of the MI. This study provides qualitative and quantitative information on the natural history of MI in rats, which should be useful as a baseline for future studies. Images Figure 1 Figure 6 Figure 2 Figure 3 Figure 4 Figure 5 PMID:619696

  14. Probability mapping of scarred myocardium using texture and intensity features in CMR images

    PubMed Central

    2013-01-01

    Background The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. Methods In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. Results In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. Conclusion The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium). PMID:24053280

  15. Living Without Creatine: Unchanged Exercise Capacity and Response to Chronic Myocardial Infarction in Creatine-Deficient Mice

    PubMed Central

    Lygate, Craig A.; Aksentijevic, Dunja; Dawson, Dana; Hove, Michiel ten; Phillips, Darci; de Bono, Joseph P.; Medway, Debra J.; Sebag-Montefiore, Liam; Hunyor, Imre; Channon, Keith M.; Clarke, Kieran; Zervou, Sevasti; Watkins, Hugh; Balaban, Robert S.; Neubauer, Stefan

    2014-01-01

    Rationale Creatine is thought to be involved in the spatial and temporal buffering of ATP in energetic organs such as heart and skeletal muscle. Creatine depletion affects force generation during maximal stimulation, while reduced levels of myocardial creatine are a hallmark of the failing heart, leading to the widely held view that creatine is important at high workloads and under conditions of pathological stress. Objective We therefore hypothesised that the consequences of creatine-deficiency in mice would be impaired running capacity, and exacerbation of heart failure following myocardial infarction. Methods and Results Surprisingly, mice with whole-body creatine deficiency due to knockout of the biosynthetic enzyme (guanidinoacetate N-methyltransferase – GAMT) voluntarily ran just as fast and as far as controls (>10km/night) and performed the same level of work when tested to exhaustion on a treadmill. Furthermore, survival following myocardial infarction was not altered, nor was subsequent LV remodelling and development of chronic heart failure exacerbated, as measured by 3D-echocardiography and invasive hemodynamics. These findings could not be accounted for by compensatory adaptations, with no differences detected between WT and GAMT−/− proteomes. Alternative phosphotransfer mechanisms were explored; adenylate kinase activity was unaltered, and although GAMT−/− hearts accumulated the creatine pre-cursor guanidinoacetate, this had negligible energy-transfer activity, while mitochondria retained near normal function. Conclusions Creatine-deficient mice show unaltered maximal exercise capacity and response to chronic myocardial infarction, and no obvious metabolic adaptations. Our results question the paradigm that creatine is essential for high workload and chronic stress responses in heart and skeletal muscle. PMID:23325497

  16. Persistent Chlamydia pneumoniae Infection of Cardiomyocytes Is Correlated with Fatal Myocardial Infarction

    PubMed Central

    Spagnoli, Luigi Giusto; Pucci, Sabina; Bonanno, Elena; Cassone, Antonio; Sesti, Fabiola; Ciervo, Alessandra; Mauriello, Alessandro

    2007-01-01

    Acute myocardial infarction (AMI) associated with unfavorable prognosis is likely to be the consequence of a diffuse active chronic inflammatory process that destabilizes the whole coronary tree and myocardium, suggesting a possible common causal agent underlying both conditions. The main objective of this study was to investigate whether Chlamydia pneumoniae (CP) infection occurred beyond the coronary plaques, namely in the myocardium of individuals who died of AMI. The presence of CP cell wall antigen (OMP-2) and CP-HSP60 was investigated in the myocardium and coronary plaques of 10 AMI and 10 age-matched control patients by immunohistochemistry, electron microscopy, and molecular biology. OMP-2 antigens were found in the unaffected myocardium of 9 of 10 AMI patients. Conversely, only 1 of 10 control patients exhibited a positive staining for CP. Moreover, OMP-2 and CP-HSP60 were detected in the whole coronary tree. CP presence was strongly associated with a T-cell inflammatory infiltrate. Our results suggest that CP may underlie both coronary and myocardial vulnerabilities in patients who died of AMI and corroborate the notion that CP may act by reducing cardiac reserves, thus worsening the ischemic burden of myocardium. PMID:17200180

  17. Prognostic impact of chronic total occlusion in a nonculprit artery in patients with acute myocardial infarction undergoing primary angioplasty.

    PubMed

    Ariza-Solé, Albert; Teruel, Luis; di Marco, Andrea; Lorente, Victòria; Sánchez-Salado, José C; Sánchez-Elvira, Guillermo; Romaguera, Rafael; Gómez-Lara, Josep; Gómez-Hospital, Joan A; Cequier, Angel

    2014-05-01

    The prognostic value of chronic total occlusion in nonculprit coronary arteries in patients with myocardial infarction undergoing primary angioplasty remains controversial. Several publications have described different methodologies and conflicting findings. In addition, causes of death were not reported. Our aim is to analyze the prognostic impact of chronic total occlusion in nonculprit coronary arteries and the role of left ventricular ejection fraction in this analysis. Prospective inclusion of consecutive patients with ST-segment elevation myocardial infarction who underwent primary angioplasty. We recorded baseline characteristics, in-hospital clinical course, and mortality and its causes during follow-up. We assessed the impact of chronic total occlusion on mortality using Cox regression analysis. Chronic total occlusion in nonculprit arteries was present in 125 of 1176 patients (10.6%); in 79 of these 125 patients, chronic total occlusion was present in the proximal segments. The mean follow-up was 339 days; 64 (5.8%) patients died during the first 6 months. Patients with chronic total occlusions had more comorbidities, poorer ventricular function, and higher mortality (hazard ratio=2.79; 95% confidence interval, 1.71-4.56). Chronic total occlusion was also associated with noncardiac death (hazard ratio=3.83; 95% confidence interval, 2.10-7.01). Chronic total occlusion in proximal segments was associated with both cardiac (hazard ratio=3.22; 95% confidence interval, 1.42-7.30) and noncardiac deaths (hazard ratio=3.43; 95% confidence interval, 1.67-7.06). The multivariate analysis performed without including left ventricular ejection fraction showed a significant association between chronic total occlusion and mortality. However, when left ventricular ejection fraction was included in the analysis, this association was nonsignificant (hazard ratio=1.76; 95% confidence interval, 0.85-3.65; P=.166). Chronic total occlusion in this clinical setting identified

  18. Cerebral flow velocities during daily activities depend on blood pressure in patients with chronic ischemic infarctions

    PubMed Central

    Novak, Vera; Hu, Kun; Desrochers, Laura; Novak, Peter; Caplan, Louis; Lipsitz, Lewis; Selim, Magdy

    2010-01-01

    Background Target blood pressure (BP) values for optimal cerebral perfusion after an ischemic stroke are still debated. We sought to examine the relationship between BP and cerebral blood flow velocities (BFV) during daily activities. Methods We studied 43 patients with chronic large vessel ischemic infarctions in middle cerebral artery (MCA) territory (aged 64.2±8.94 years; at 6.1±4.9 years after stroke), and 67 age-matched controls. BFV in MCAs were measured during supine baseline, sitting, standing and tilt. A regression analysis and a dynamic phase analysis were used to quantify BP-BFV relationship. Results The mean arterial pressure was similar between the groups (89±15 mmHg). Baseline BFV were lower by ~ 30% in the stroke patients compared to the controls (p=0.0001). BFV declined further with postural changes, and remained lower in the stroke group during sitting (p=0.003), standing (p=0.003) and tilt (p=0.002) as compared to the control group. Average BFV on the stroke side were positively correlated with BP during baseline (R=0.54, p=0.0022, the slope 0.46 cm/s/mm Hg) and tilt (R=0.52, p=0.0028, the slope 0.40 cm/s/mm Hg). Regression analysis suggested that BFV may increase ~ 30-50% at mean BP > 100 mmHg. Orthostatic hypotension during the first minute of tilt or standing was independently associated with lower BFV on the stroke side (p=0.0008). Baseline BP-BFV phase shift derived from the phase analysis was smaller on the stroke-side (p=0.0006). Conclusion We found that BFV are lower in stroke patients and daily activities such as standing could induce hypoperfusion. BFV increase with mean arterial pressure > 100 mmHg. Dependency of BFV on arterial pressure may have implications for BP management after stroke. Further prospective investigations are needed to determine the impact of these findings on functional recovery and strategies to improve perfusion pressure during daily activities after ischemic stroke. PMID:19959536

  19. A rare long-term survival of the life-threatening trio: silent myocardial infarction complicated by ventricular septal rupture, type 2 diabetes mellitus and chronic bronchitis.

    PubMed

    Rayhan, Md Abdur Rob; He, Yong-Ming; Yang, Xiang-Jun; Zhou, Bing-Yuan; Zhao, Xin; Xu, Hai-Feng; Du, Xiao-Jiao; Qian, Yun-Xia

    2015-09-01

    Silent myocardial infarction followed by ventricular septal rupture (VSR) is a rare phenomenon. In the absence of a timely diagnosis and surgical correction, the short term mortality of such patients is greater than 90%. We present one such unique case of a patient with an asymptomatic myocardial infarction complicated by VSR, type 2 diabetes mellitus and chronic bronchitis. Unfortunately, this possibly life-threatening condition had been misdiagnosed for more than one month after initial medical contact. Lack of typical symptoms of chest pain and chronic bronchitis is primarily responsible for this long-time misdiagnosis. We want to emphasize the importance of systematic diagnostic work-up, high vigilance for possibility of VSR complicating myocardial infarction in aged patients with diabetes and chronic bronchitis, which may mislead doctors' judgments and put patients at high risk.

  20. p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53-Lys(118) acetylation.

    PubMed

    Gogna, Rajan; Madan, Esha; Khan, Mahmood; Pati, Uttam; Kuppusamy, Periannan

    2013-11-01

    Myocardial infarction, an irreversible cardiac tissue damage, involves progressive loss of cardiomyocytes due to p53-mediated apoptosis. Oxygenation is known to promote cardiac survival through activation of NOS3 gene. We hypothesized a dual role for p53, which, depending on oxygenation, can elicit apoptotic death signals or NOS3-mediated survival signals in the infarct heart. p53 exhibited a differential DNA-binding, namely, BAX-p53RE in the infarct heart or NOS3-p53RE in the oxygenated heart, which was regulated by oxygen-induced, post-translational modification of p53. In the infarct heart, p53 was heavily acetylated at Lys(118) residue, which was exclusively reversed in the oxygenated heart, apparently regulated by oxygen-dependent expression of TIP60. The inhibition of Lys(118) acetylation promoted the generation of NOS3-promoting prosurvival form of p53. Thus, oxygenation switches p53-DNA interaction by regulating p53 core-domain acetylation, promoting a prosurvival transcription activity of p53. Understanding this novel oxygen-p53 survival pathway will open new avenues in cardioprotection molecular therapy.

  1. p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53-Lys118 acetylation

    PubMed Central

    Gogna, Rajan; Madan, Esha; Khan, Mahmood; Pati, Uttam; Kuppusamy, Periannan

    2013-01-01

    Myocardial infarction, an irreversible cardiac tissue damage, involves progressive loss of cardiomyocytes due to p53-mediated apoptosis. Oxygenation is known to promote cardiac survival through activation of NOS3 gene. We hypothesized a dual role for p53, which, depending on oxygenation, can elicit apoptotic death signals or NOS3-mediated survival signals in the infarct heart. p53 exhibited a differential DNA-binding, namely, BAX-p53RE in the infarct heart or NOS3-p53RE in the oxygenated heart, which was regulated by oxygen-induced, post-translational modification of p53. In the infarct heart, p53 was heavily acetylated at Lys118 residue, which was exclusively reversed in the oxygenated heart, apparently regulated by oxygen-dependent expression of TIP60. The inhibition of Lys118 acetylation promoted the generation of NOS3-promoting prosurvival form of p53. Thus, oxygenation switches p53-DNA interaction by regulating p53 core-domain acetylation, promoting a prosurvival transcription activity of p53. Understanding this novel oxygen-p53 survival pathway will open new avenues in cardioprotection molecular therapy. PMID:24096875

  2. Correlation of Scar in Cardiac MRI and High‐Resolution Contact Mapping of Left Ventricle in a Chronic Infarct Model

    PubMed Central

    THAJUDEEN, ANEES; STEWART, BRIAN; COKIC, IVAN; NAKAGAWA, HIROSHI; SHEHATA, MICHAEL; AMORN, ALLEN M.; KALI, AVINASH; LIU, EZH; HARLEV, DORON; BENNETT, NATHAN; DHARMAKUMAR, ROHAN; CHUGH, SUMEET S.; WANG, XUNZHANG

    2015-01-01

    Background Endocardial mapping for scars and abnormal electrograms forms the most essential component of ventricular tachycardia ablation. The utility of ultra‐high resolution mapping of ventricular scar was assessed using a multielectrode contact mapping system in a chronic canine infarct model. Methods Chronic infarcts were created in five anesthetized dogs by ligating the left anterior descending coronary artery. Late gadolinium‐enhanced magnetic resonance imaging (LGE MRI) was obtained 4.9 ± 0.9 months after infarction, with three‐dimensional (3D) gadolinium enhancement signal intensity maps at 1‐mm and 5‐mm depths from the endocardium. Ultra‐high resolution electroanatomical maps were created using a novel mapping system (Rhythmia Mapping System, Rhythmia Medical/Boston Scientific, Marlborough, MA, USA) Rhythmia Medical, Boston Scientific, Marlborough, MA, USA with an 8.5F catheter with mini‐basket electrode array (64 tiny electrodes, 2.5‐mm spacing, center‐to‐center). Results The maps contained 7,754 ± 1,960 electrograms per animal with a mean resolution of 2.8 ± 0.6 mm. Low bipolar voltage (<2 mV) correlated closely with scar on the LGE MRI and the 3D signal intensity map (1‐mm depth). The scar areas between the MRI signal intensity map and electroanatomic map matched at 87.7% of sites. Bipolar and unipolar voltages, compared in 592 electrograms from four MRI‐defined scar types (endocardial scar, epicardial scar, mottled transmural scar, and dense transmural scar) as well as normal tissue, were significantly different. A unipolar voltage of <13 mV correlated with transmural extension of scar in MRI. Electrograms exhibiting isolated late potentials (ILPs) were manually annotated and ILP maps were created showing ILP location and timing. ILPs were identified in 203 ± 159 electrograms per dog (within low‐voltage areas) and ILP maps showed gradation in timing of ILPs at different locations in the scar. Conclusions Ultra

  3. Correlation of scar in cardiac MRI and high-resolution contact mapping of left ventricle in a chronic infarct model.

    PubMed

    Thajudeen, Anees; Jackman, Warren M; Stewart, Brian; Cokic, Ivan; Nakagawa, Hiroshi; Shehata, Michael; Amorn, Allen M; Kali, Avinash; Liu, Ezh; Harlev, Doron; Bennett, Nathan; Dharmakumar, Rohan; Chugh, Sumeet S; Wang, Xunzhang

    2015-06-01

    Endocardial mapping for scars and abnormal electrograms forms the most essential component of ventricular tachycardia ablation. The utility of ultra-high resolution mapping of ventricular scar was assessed using a multielectrode contact mapping system in a chronic canine infarct model. Chronic infarcts were created in five anesthetized dogs by ligating the left anterior descending coronary artery. Late gadolinium-enhanced magnetic resonance imaging (LGE MRI) was obtained 4.9 ± 0.9 months after infarction, with three-dimensional (3D) gadolinium enhancement signal intensity maps at 1-mm and 5-mm depths from the endocardium. Ultra-high resolution electroanatomical maps were created using a novel mapping system (Rhythmia Mapping System, Rhythmia Medical/Boston Scientific, Marlborough, MA, USA) Rhythmia Medical, Boston Scientific, Marlborough, MA, USA with an 8.5F catheter with mini-basket electrode array (64 tiny electrodes, 2.5-mm spacing, center-to-center). The maps contained 7,754 ± 1,960 electrograms per animal with a mean resolution of 2.8 ± 0.6 mm. Low bipolar voltage (<2 mV) correlated closely with scar on the LGE MRI and the 3D signal intensity map (1-mm depth). The scar areas between the MRI signal intensity map and electroanatomic map matched at 87.7% of sites. Bipolar and unipolar voltages, compared in 592 electrograms from four MRI-defined scar types (endocardial scar, epicardial scar, mottled transmural scar, and dense transmural scar) as well as normal tissue, were significantly different. A unipolar voltage of <13 mV correlated with transmural extension of scar in MRI. Electrograms exhibiting isolated late potentials (ILPs) were manually annotated and ILP maps were created showing ILP location and timing. ILPs were identified in 203 ± 159 electrograms per dog (within low-voltage areas) and ILP maps showed gradation in timing of ILPs at different locations in the scar. Ultra-high resolution contact electroanatomical mapping accurately localizes

  4. Can Chronic Remote Cortical Hypoperfusion Induced by Thalamic Infarction Cause Damage of Tracts Passing through Those Hypoperfused Regions?

    PubMed

    Magnin, Eloi; Chamard, Ludivine; Vuillier, Fabrice; Tatu, Laurent; Berger, Eric

    2013-01-01

    We report the case of a woman presenting with changes on cerebral imaging a year and a half after a bi-thalamic (predominantly left-sided) infarction including lateral and medial thalamic nuclei. Lateral geniculate body and pulvinar were not damaged. Hypoperfusion was observed in left cortical and basal structures. White matter FLAIR hyperintense lesions occurred in the left hemisphere and the occipital region 1 year and half after stroke. Medial and lateral thalamic nuclei are not highly connected to the occipital cortex. Therefore, in addition to Wallerian degeneration after thalamic stroke, we hypothesize that the chronic left temporal hypoperfusion induced by diaschisis can lead to a lateralized chronic hypoxic damage of the occipital fiber tract (optic radiation) that passes through the temporal lobe.

  5. Interaction of chronic total occlusion and chronic kidney disease in patients undergoing primary percutaneous coronary intervention for acute ST-elevation myocardial infarction.

    PubMed

    Bataille, Yoann; Plourde, Guillaume; Machaalany, Jimmy; Abdelaal, Eltigani; Déry, Jean-Pierre; Larose, Eric; Déry, Ugo; Noël, Bernard; Barbeau, Gérald; Roy, Louis; Costerousse, Olivier; Bertrand, Olivier F

    2013-07-15

    Chronic total occlusion (CTO) in a non-infarct-related artery and chronic kidney failure (CKD) are associated with worse outcomes after primary percutaneous coronary intervention (PCI). The aim of this study was to investigate the interaction of CTO and CKD in patients who underwent primary PCI for acute ST-segment elevation myocardial infarction (STEMI). Patients with STEMIs with or without CKD, defined as an estimated glomerular filtration rate <60 ml/min/1.73 m(2), were categorized into those with single-vessel disease and those with multivessel disease with or without CTO. The primary outcomes were the incidence of 30-day and 1-year mortality. Among 1,873 consecutive patients with STEMIs included between 2006 and 2011, 336 (18%) had CKD. The prevalence of CTO in a non-infarct-related artery was 13% in patients with CKD compared with 7% in those without CKD (p = 0.0003). There was a significant interaction between CKD and CTO on 30-day mortality (p = 0.018) and 1-year mortality (p = 0.013). Independent predictors of late mortality in patients with CKD were previous myocardial infarction (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.01 to 2.79), age >75 years (HR 1.86, 95% CI 1.19 to 2.95), a left ventricular ejection fraction after primary PCI <40% (HR 2.20, 95% CI 1.36 to 3.63), left main culprit artery (HR 4.46, 95% CI 1.64 to 10.25), and shock (HR 7.44, 95% CI 4.56 to 12.31), but multivessel disease with CTO was not a predictor. In contrast, multivessel disease with CTO was an independent predictor of mortality in patients without CKD (HR 3.30, 95% CI 1.70 to 6.17). In conclusion, in patients with STEMIs who underwent primary PCI, with preexisting CKD, the prevalence of CTO in a non-infarct-related artery was twice as great. In these patients, the clinical impact of CTO seems to be overshadowed by the presence of CKD. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. High temporal resolution breathheld 3D FIESTA CINE imaging: validation of ventricular function in patients with chronic myocardial infarction.

    PubMed

    Rettmann, Dan W; Saranathan, Manojkumar; Wu, Katherine C; Azevedo, Clerio F; Bluemke, David A; Foo, Thomas K F

    2007-06-01

    To develop a gated single-breathhold, high temporal resolution three-dimensional (3D) CINE imaging technique and to evaluate its accuracy in volumetric and functional quantification in patients with chronic myocardial infarction. A 3D CINE steady-state free precession (SSFP) pulse sequence was developed incorporating variable temporal sampling of the low and high spatial frequency k-space data to reduce breathhold time and parallel imaging to increase temporal resolution. Reconstruction with retrospective interpolation enabled complete R-R interval coverage. Feasibility was assessed in eight patients with chronic myocardial infarction and ventricular functional values were compared to those of a 2D CINE acquisition. There was no significant difference between the 3D CINE and 2D CINE for end-diastolic volume (168 +/- 73 vs. 177 +/- 59 mL, respectively; P < 0.27), end-systolic volume (81 +/- 62 vs. 79 +/- 53 mL; P < 0.81), and ejection fraction (EF) measurements (55 +/- 14% vs. 58 +/- 14%; P < 0.14). The mean difference in EF was less than 2.5%. A wall motion assessment indicated a good agreement, with a weighted kappa value of 0.62. High temporal resolution 3D CINE SSFP imaging of the whole heart can be obtained in a single breathhold and yield ventricular function measurements similar to 2D CINE methods. (c) 2007 Wiley-Liss, Inc.

  7. Impact of microvascular obstruction on semiautomated techniques for quantifying acute and chronic myocardial infarction by cardiovascular magnetic resonance

    PubMed Central

    Bulluck, Heerajnarain; Rosmini, Stefania; Abdel-Gadir, Amna; Bhuva, Anish N; Treibel, Thomas A; Fontana, Marianna; Weinmann, Shane; Sirker, Alex; Herrey, Anna S; Manisty, Charlotte; Moon, James C; Hausenloy, Derek J

    2016-01-01

    Aims The four most promising semiautomated techniques (5-SD, 6-SD, Otsu and the full width half maximum (FWHM)) were compared in paired acute and follow-up cardiovascular magnetic resonance (CMR), taking into account the impact of microvascular obstruction (MVO) and using automated extracellular volume fraction (ECV) maps for reference. Furthermore, their performances on the acute scan were compared against manual myocardial infarct (MI) size to predict adverse left ventricular (LV) remodelling (≥20% increase in end-diastolic volume). Methods 40 patients with reperfused ST segment elevation myocardial infarction (STEMI) with a paired acute (4±2 days) and follow-up CMR scan (5±2 months) were recruited prospectively. All CMR analysis was performed on CVI42. Results Using manual MI size as the reference standard, 6-SD accurately quantified acute (24.9±14.0%LV, p=0.81, no bias) and chronic MI size (17.2±9.7%LV, p=0.88, no bias). The performance of FWHM for acute MI size was affected by the acquisition sequence used. Furthermore, FWHM underestimated chronic MI size in those with previous MVO due to the significantly higher ECV in the MI core on the follow-up scans previously occupied by MVO (82 (75–88)% vs 62 (51–68)%, p<0.001). 5-SD and Otsu were precise but overestimated acute and chronic MI size. All techniques were performed with high diagnostic accuracy and equally well to predict adverse LV remodelling. Conclusions 6-SD was the most accurate for acute and chronic MI size and should be the preferred semiautomatic technique in randomised controlled trials. However, 5-SD, FWHM and Otsu could also be used when precise MI size quantification may be adequate (eg, observational studies). PMID:28008358

  8. Myocardium at risk in ST-segment elevation myocardial infarction comparison of T2-weighted edema imaging with the MR-assessed endocardial surface area and validation against angiographic scoring.

    PubMed

    Fuernau, Georg; Eitel, Ingo; Franke, Vinzenz; Hildebrandt, Lysann; Meissner, Josefine; de Waha, Suzanne; Lurz, Philipp; Gutberlet, Matthias; Desch, Steffen; Schuler, Gerhard; Thiele, Holger

    2011-09-01

    The objective of this study was to assess the area at risk (AAR) in ST-segment elevation myocardial infarction with 2 different cardiac magnetic resonance (CMR) imaging methods and to compare them with the validated angiographic Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) in a large consecutive patient cohort. Edema imaging with T(2)-weighted CMR and the endocardial surface area (ESA) assessed by late gadolinium enhancement have been introduced as relatively new methods for AAR assessment in ST-segment elevation myocardial infarction. However, data on the utility and validation of these techniques are limited. A total of 197 patients undergoing primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction were included. AAR (assessed with T(2)-weighted edema imaging and the ESA method), infarct size, and myocardial salvage (AAR minus infarct size) were determined by CMR 2 to 4 days after primary angioplasty. Angiographic AAR scoring was performed by use of the APPROACH-score. All measurements were done offline by blinded observers. The AAR assessed by T(2)-weighted imaging showed good correlation with the angiographic AAR (r = 0.87; p < 0.001), whereas the ESA showed only a moderate correlation either to T(2)-weighted imaging (r = 0.56; p < 0.001) or the APPROACH-score (r = 0.44; p < 0.001). Mean AAR by ESA (20.0 ± 11.7% of left ventricular mass) was significantly (p < 0.001) smaller than the AAR assessed by T(2)-weighted imaging (35.6 ± 10.9% of left ventricular mass) or the APPROACH-score (27.9 ± 10.5% of left ventricular mass) and showed a significant negative dependence on myocardial salvage index. In contrast, no dependence of T(2)-weighted edema imaging or the APPROACH-score on myocardial salvage index was seen. The AAR can be reliably assessed by T(2)-weighted CMR, whereas assessment of the AAR by ESA seems to be dependent on the degree of myocardial salvage, thereby

  9. 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

    SciTech Connect

    Okura, Hanayuki; Saga, Ayami; Soeda, Mayumi; Miyagawa, Shigeru; Sawa, Yoshiki; Daimon, Takashi; Ichinose, Akihiro; Matsuyama, Akifumi

    2012-09-07

    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 of 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

  10. [Neurogenic stunned myocardium].

    PubMed

    Ruiz Bailén, M; Rucabado Aguilar, L; López Martínez, A

    2006-01-01

    The existence of stunned myocardium and reversible myocardial dysfunction is widely described and accepted in patients suffering ischemic heart disease. However, it cannot be exclusive to coronary disease. Classically, the appearance of electrocardiographic changes in the critical neurological disease has been described. However, at present, it seems to be observed that some of these patients with critical neurological disease could have variable grades of myocardial dysfunction, which is generally reversible in the surviving patients. This myocardial dysfunction, which could affect critically ill neurological patients, has traits similar to stunned myocardium generated in coronary patients since: a) it is generally associated to electrocardiographic changes, b) it can be accompanied by segmental contractility disorders and even c) it may be accompanied by a certain increase of cardiac biomarkers. Although its etiopathogeny is unknown, it could be related with the severity of the primary neurological disease. Its prophylaxis and prognosis are also unknown. It could be related with neurogenic edema, with hemodynamic instability, and could also play a very important role in brain death and in organ donation.

  11. Observations on the effects of CO2-laser on rat myocardium.

    PubMed

    Owen, E R; Canfield, P; Bryant, K; Hopwood, P R

    1984-01-01

    The effect of CO2-laser burn on rat myocardium was studied to evaluate a hypothesis developed by Mirhoseini and Cayton that infarcted myocardium may be revascularized by establishing an alternative circulation from a ventricle to the coronary arteries by means of laser channels burned through the myocardium. The hearts of 22 rats were examined histologically for a period ranging from a few minutes to 50 days after CO2 laser was applied to the myocardium. The laser initiated an intense inflammatory response in the myocardium adjacent to the target site. The authors believe that the inflammatory response, observed in this study to the Biophy-Las 80 surgical laser, must be reduced if laser is to be an effective means of myocardial revascularization.

  12. Parkin Regulates Mitochondrial Autophagy After Myocardial Infarction in Rats.

    PubMed

    Wu, Li; Maimaitirexiati, Xiemuziya; Jiang, Yun; Liu, Liang

    2016-05-08

    BACKGROUND To study the role of Parkin in the regulation of mitochondrial autophagy in the heart by assessing mitochondrial autophagy and changes in Parkin protein expression in rat myocardium after myocardial infarction (MI). MATERIAL AND METHODS Rats were randomly assigned to three groups: control, sham, and MI. Four weeks after induction of MI, ultrasonic examination of the rats was performed to measure left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and left ventricular diastolic/systolic volume. Rat myocardium was collected from each group and examined for changes in morphology, size, and amount of mitochondria and autophagosomes by transmission electronic microscopy. A Western blot was performed to analyze the levels of Parkin and the autophagy-related protein LC3. RESULTS Four weeks after MI, cardiac function of the MI rats was impaired compared with the control rats. Both LVESD and LVEDD were elevated in the MI rats (p<0.05) while EF was decreased, indicating that the MI model was constructed successfully. After MI, increased numbers of mitochondria and autophagosomes were observed in the myocardium (p<0.05), and the mitochondrial morphology was destroyed. Chloroquine (CQ) treatment increased the number of autophagosomes in the myocardium of the control rats (p<0.05) but not in MI rats (p>0.05). In addition, the levels of the autophagy-related proteins LC3II/LC3I were elevated in the myocardium after MI (p<0.05) and the activity of Parkin was significantly reduced (p<0.05). CONCLUSIONS Under conditions of chronic MI, mitochondrial dysfunction and disruption of autophagosomal clearance are associated with Parkin expression.

  13. Iron Deposition following Chronic Myocardial Infarction as a Substrate for Cardiac Electrical Anomalies: Initial Findings in a Canine Model

    PubMed Central

    Wang, Xunzhang; Yang, Hsin-Jung; Tang, Richard L. Q.; Thajudeen, Anees; Shehata, Michael; Amorn, Allen M.; Liu, Enzhao; Stewart, Brian; Bennett, Nathan; Harlev, Doron; Tsaftaris, Sotirios A.; Jackman, Warren M.; Chugh, Sumeet S.; Dharmakumar, Rohan

    2013-01-01

    Purpose Iron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. Methods Two groups of dogs (ex-vivo (n = 12) and in-vivo (n = 10)) were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity () and conductivity (). Mass spectrometry was used to classify and characterize tissue sections with (IRON+) and without (IRON-) iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR) for estimation of scar volume (late-gadolinium enhancement, LGE) and iron deposition (T2*) relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR), QT interval (QT), QT corrected for HR (QTc) and QTc dispersion (QTcd). In a fraction of these animals (n = 5), ultra-high resolution electroanatomical mapping (EAM) was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs). Results Compared to IRON- sections, IRON+ sections had higher, but no difference in. A linear relationship was found between iron content and (p<0.001), but not (p = 0.34). Among two groups of animals (Iron (<1.5%) and Iron (>1.5%)) with similar scar volumes (7.28%±1.02% (Iron (<1.5%)) vs 8.35%±2.98% (Iron (>1.5%)), p = 0.51) but markedly different iron volumes (1.12%±0.64% (Iron (<1.5%)) vs 2.47%±0.64% (Iron (>1.5%)), p = 0.02), QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05). EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron. Conclusion The electrical behavior of infarcted hearts with iron appears to

  14. Iron deposition following chronic myocardial infarction as a substrate for cardiac electrical anomalies: initial findings in a canine model.

    PubMed

    Cokic, Ivan; Kali, Avinash; Wang, Xunzhang; Yang, Hsin-Jung; Tang, Richard L Q; Thajudeen, Anees; Shehata, Michael; Amorn, Allen M; Liu, Enzhao; Stewart, Brian; Bennett, Nathan; Harlev, Doron; Tsaftaris, Sotirios A; Jackman, Warren M; Chugh, Sumeet S; Dharmakumar, Rohan

    2013-01-01

    Iron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. Two groups of dogs (ex-vivo (n = 12) and in-vivo (n = 10)) were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity ([Formula: see text]) and conductivity ([Formula: see text]). Mass spectrometry was used to classify and characterize tissue sections with (IRON+) and without (IRON-) iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR) for estimation of scar volume (late-gadolinium enhancement, LGE) and iron deposition (T2*) relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR), QT interval (QT), QT corrected for HR (QTc) and QTc dispersion (QTcd). In a fraction of these animals (n = 5), ultra-high resolution electroanatomical mapping (EAM) was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs). Compared to IRON- sections, IRON+ sections had higher[Formula: see text], but no difference in[Formula: see text]. A linear relationship was found between iron content and [Formula: see text] (p<0.001), but not [Formula: see text] (p = 0.34). Among two groups of animals (Iron (<1.5%) and Iron (>1.5%)) with similar scar volumes (7.28% ± 1.02% (Iron (<1.5%)) vs 8.35% ± 2.98% (Iron (>1.5%)), p = 0.51) but markedly different iron volumes (1.12% ± 0.64% (Iron (<1.5%)) vs 2.47% ± 0.64% (Iron (>1.5%)), p = 0.02), QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05). EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron

  15. Myocardial ischemia, reperfusion, and infarction in chronically instrumented, intact, conscious, and unrestrained mice

    PubMed Central

    Lujan, Heidi L.; Janbaih, Hussein; Feng, Han-Zhong; Jin, Jian-Ping

    2012-01-01

    In the United States alone, the National Heart, Lung, and Blood Institute (NHLBI) has invested several hundred million dollars in pursuit of myocardial infarct-sparing therapies. However, due largely to methodological limitations, this investment has not produced any notable clinical application or cardioprotective therapy. Among the major methodological limitations is the reliance on animal models that do not mimic the clinical situation. In this context, the limited use of conscious animal models is of major concern. In fact, whenever possible, studies of cardiovascular physiology and pathophysiology should be conducted in conscious, complex models to avoid the complications associated with the use of anesthesia and surgical trauma. The mouse has significant advantages over other experimental models for the investigation of infarct-sparing therapies. The mouse is inexpensive, has a high throughput, and presents the ability of one to create genetically modified models. However, successful infarct-sparing therapies in anesthetized mice or isolated mouse hearts may not be successful in more complex models, including conscious mice. Accordingly, a conscious mouse model of myocardial ischemia and reperfusion has the potential to be of major importance for advancing the concepts and methods that drive the development of infarct-sparing therapies. Therefore, we describe, for the first time, the use of an intact, conscious, and unrestrained mouse model of myocardial ischemia-reperfusion and infarction. The conscious mouse model permits occlusion and reperfusion of the left anterior descending coronary artery in an intact, complex model free of the confounding influences of anesthetics and surgical trauma. This methodology may be adopted for advancing the concepts and ideas that drive cardiovascular research. PMID:22538514

  16. Myocardial ischemia, reperfusion, and infarction in chronically instrumented, intact, conscious, and unrestrained mice.

    PubMed

    Lujan, Heidi L; Janbaih, Hussein; Feng, Han-Zhong; Jin, Jian-Ping; DiCarlo, Stephen E

    2012-06-15

    In the United States alone, the National Heart, Lung, and Blood Institute (NHLBI) has invested several hundred million dollars in pursuit of myocardial infarct-sparing therapies. However, due largely to methodological limitations, this investment has not produced any notable clinical application or cardioprotective therapy. Among the major methodological limitations is the reliance on animal models that do not mimic the clinical situation. In this context, the limited use of conscious animal models is of major concern. In fact, whenever possible, studies of cardiovascular physiology and pathophysiology should be conducted in conscious, complex models to avoid the complications associated with the use of anesthesia and surgical trauma. The mouse has significant advantages over other experimental models for the investigation of infarct-sparing therapies. The mouse is inexpensive, has a high throughput, and presents the ability of one to create genetically modified models. However, successful infarct-sparing therapies in anesthetized mice or isolated mouse hearts may not be successful in more complex models, including conscious mice. Accordingly, a conscious mouse model of myocardial ischemia and reperfusion has the potential to be of major importance for advancing the concepts and methods that drive the development of infarct-sparing therapies. Therefore, we describe, for the first time, the use of an intact, conscious, and unrestrained mouse model of myocardial ischemia-reperfusion and infarction. The conscious mouse model permits occlusion and reperfusion of the left anterior descending coronary artery in an intact, complex model free of the confounding influences of anesthetics and surgical trauma. This methodology may be adopted for advancing the concepts and ideas that drive cardiovascular research.

  17. Sustained myocardial production of stromal cell-derived factor-1α was associated with left ventricular adverse remodeling in patients with myocardial infarction.

    PubMed

    Uematsu, Manabu; Yoshizaki, Toru; Shimizu, Takuya; Obata, Jun-ei; Nakamura, Takamitsu; Fujioka, Daisuke; Watanabe, Kazuhiro; Watanabe, Yosuke; Kugiyama, Kiyotaka

    2015-11-15

    The role of stromal cell-derived factor-1α (SDF-1α) expressed in infarcted myocardium is unknown in humans. We examined whether SDF-1α produced in an infarcted myocardial lesion may play a role in left ventricle (LV) remodeling and dysfunction in patients with acute myocardial infarction (AMI). We measured SDF-1α levels in plasma obtained from aortic root (AO) and anterior interventricular vein (AIV) in the early phase (2 wk after MI) and the chronic phase (6 mo after MI) in 80 patients with anterior MI. An increment in SDF-1α level from AO to AIV, reflecting SDF-1α release from infarcted myocardium, was more frequent in patients with MI in the early phase of MI [n = 52 (65%), P = 0.03] but not in the chronic phase of MI [n = 46 (58%), P = 0.11] compared with that in control patients [n = 6/17 (35%)]. On linear regression analysis, the transmyocardial gradient in SDF-1α level in the chronic phase of MI was correlated with percentage changes in LV end-diastolic volume index (r = 0.39, P < 0.001), LV end-systolic volume index (r = 0.38, P < 0.001), and LV ejection fraction (r = -0.26, P = 0.01) 6 mo after AMI. By contrast, the transmyocardial gradient of SDF-1α in the early phase of MI had no significant correlations. In conclusion, the production of SDF-1α in infarcted myocardium in the chronic phase of MI was associated with LV adverse remodeling and progressive dysfunction in AMI survivors.

  18. 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.

    PubMed

    Okura, Hanayuki; Saga, Ayami; Soeda, Mayumi; Miyagawa, Shigeru; Sawa, Yoshiki; Daimon, Takashi; Ichinose, Akihiro; Matsuyama, Akifumi

    2012-09-07

    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 of 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.

  19. Involvement of protein kinase C in the delayed cytoprotection following sublethal ischaemia in rabbit myocardium.

    PubMed Central

    Baxter, G. F.; Goma, F. M.; Yellon, D. M.

    1995-01-01

    Rabbit hearts were preconditioned with four 5 min coronary artery occlusions 24 h before 30 min coronary occlusion with 120 min reperfusion. Preconditioning significantly reduced the percentage of myocardium infarcting within the risk zone from 49.1 +/- 4.3% to 31.8 +/- 3.5% (P < 0.05). When the protein kinase C (PKC) inhibitor, chelerythrine, was administered just before preconditioning, the delayed protection against infarction 24 h later was abolished. We conclude that the delayed cytoprotective response associated with ischaemic preconditioning of myocardium is likely to involve the early activation of one or more PKC subtypes. PMID:7545515

  20. Three-dimensional segmentation of the left ventricle in late gadolinium enhanced MR images of chronic infarction combining long- and short-axis information.

    PubMed

    Wei, Dong; Sun, Ying; Ong, Sim-Heng; Chai, Ping; Teo, Lynette L; Low, Adrian F

    2013-08-01

    Automatic segmentation of the left ventricle (LV) in late gadolinium enhanced (LGE) cardiac MR (CMR) images is difficult due to the intensity heterogeneity arising from accumulation of contrast agent in infarcted myocardium. In this paper, we present a comprehensive framework for automatic 3D segmentation of the LV in LGE CMR images. Given myocardial contours in cine images as a priori knowledge, the framework initially propagates the a priori segmentation from cine to LGE images via 2D translational registration. Two meshes representing respectively endocardial and epicardial surfaces are then constructed with the propagated contours. After construction, the two meshes are deformed towards the myocardial edge points detected in both short-axis and long-axis LGE images in a unified 3D coordinate system. Taking into account the intensity characteristics of the LV in LGE images, we propose a novel parametric model of the LV for consistent myocardial edge points detection regardless of pathological status of the myocardium (infarcted or healthy) and of the type of the LGE images (short-axis or long-axis). We have evaluated the proposed framework with 21 sets of real patient and four sets of simulated phantom data. Both distance- and region-based performance metrics confirm the observation that the framework can generate accurate and reliable results for myocardial segmentation of LGE images. We have also tested the robustness of the framework with respect to varied a priori segmentation in both practical and simulated settings. Experimental results show that the proposed framework can greatly compensate variations in the given a priori knowledge and consistently produce accurate segmentations.

  1. Idiopathic bilateral chronic subdural hematoma with left internal carotid artery infarct in a 3 months infant: A rare case report

    PubMed Central

    Kumar, Mahesh; Yadav, Krishan; Verma, Saurabh Kumar; Maheshwari, Vikas

    2016-01-01

    Spontaneous chronic subdural hematoma (CSH) in infants is extremely rare. A very limited number of cases are known and reported in literature. The clinical presentation can be myriad varying from asymptomatic cases to gross neurological deficits. We report a case of a 3-month-old child who presented to us with repeated episodes of focal seizures of the left upper and lower limb of 1 month duration. Subsequent imaging revealed bilateral CSH (right > left) with left internal carotid artery infarct and midline shift to left by 8 mm. The child improved following burr hole evacuation of the right-sided CSH. The management of such case and a brief review of literature are discussed. PMID:28217168

  2. Increased expression of Dock180 protein in the noninfarcted myocardium in rats.

    PubMed

    Liu, Xiao-Lan; Li, Gang; Wang, Zhi-Hua; Zhao, Wen-Ju; Wang, Li-Ping

    2013-03-01

    The integrin β1 subunit and its downstream molecule focal adhesion kinase have been identified as critical molecules for the inhibition of postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure. However, as a component of the integrin pathway, it is still unclear whether Dock180 (dedicator of cytokinesis 1) protein is expressed in the noninfarcted myocardium of the peri-infarct zones. In this study, experimental myocardial infarction (MI) and sham-operation (sham) models were established in Sprague Dawley rats and the expression of Dock180 protein in the myocardium of the sham group and in the noninfarcted myocardium of the peri-infarct zones of the MI group was detected by Western blot technique. The Dock180 protein expression in the myocardium was as follows: postsham 24-hour group, 0.10 ± 0.04 (n = 8); post-MI 24-hour group, 0.13 ± 0.03 (n = 8); postsham 12-week group, 0.11 ± 0.05 (n = 8); and post-MI 12-week group 0.17 ± 0.04 (n = 8). The Dock180 protein expression in the myocardium in the post-MI 12-week group was significantly higher than that in the postsham 12-week group (p = 0.019), in the postsham 24-hour group (p = 0.004), and in the post-MI 24-hour group (p = 0.040). We conclude that Dock180 protein is expressed in the myocardium in rats. Furthermore, its expression is significantly increased in the noninfarcted myocardium of the peri-infarct zones.

  3. Evaluation of monoenergetic late iodine enhancement dual-energy computed tomography for imaging of chronic myocardial infarction.

    PubMed

    Wichmann, Julian L; Arbaciauskaite, Ruta; Kerl, J Matthias; Frellesen, Claudia; Bodelle, Boris; Lehnert, Thomas; Monsefi, Nadejda; Vogl, Thomas J; Bauer, Ralf W

    2014-06-01

    To evaluate image quality and diagnostic accuracy of selective monoenergetic reconstructions of late iodine enhancement (LIE) dual-energy computed tomography (DECT) for imaging of chronic myocardial infarction (CMI). Twenty patients with a history of coronary bypass surgery underwent cardiac LIE-DECT and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI). LIE-DECT images were reconstructed as selective monoenergetic spectral images with photon energies of 40, 60, 80, and 100 keV and the standard linear blending setting (M_0.6). Images were assessed for late enhancement, transmural extent, signal characteristics and subjective image quality. Seventy-nine myocardial segments (23 %) showed LGE. LIE-DECT detected 76 lesions. Images obtained at 80 keV and M_0.6 showed a high signal-to-noise ratio (15.9; 15.1), contrast-to-noise ratio (4.2; 4.0) and sensitivity (94.9 %; 92.4 %) while specificity was identical (99.6 %). Differences between these series were not statistically significant. Transmural extent of LIE was overestimated in both series (80 keV: 40 %; M_0.6: 35 %) in comparison to MRI. However, observers preferred 80 keV in 13/20 cases (65 %, κ = 0.634) over M_0.6 (4/20 cases) regarding subjective image quality. Post-processing of LIE-DECT data with selective monoenergetic reconstructions at 80 keV significantly improves subjective image quality while objective image quality shows no significant difference compared to standard linear blending. Late enhancement dual-energy CT allows for detection of chronic myocardial infarction. Monoenergetic reconstructions at 80 keV significantly improve subjective image quality. 80 keV and standard linear blending reconstructions show no significant differences. Extent of CMI detected with LIE-DECT is overestimated compared with MRI.

  4. Medication regimen complexity and readmissions after hospitalization for heart failure, acute myocardial infarction, pneumonia, and chronic obstructive pulmonary disease.

    PubMed

    Abou-Karam, Nada; Bradford, Chad; Lor, Kajua B; Barnett, Mitchell; Ha, Michelle; Rizos, Albert

    2016-01-01

    Readmission rate is increasingly being viewed as a key indicator of health system performance. Medication regimen complexity index scores may be predictive of readmissions; however, few studies have examined this potential association. The primary objective of this study was to determine whether medication regimen complexity index is associated with all-cause 30-day readmission after admission for heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. This study was an institutional review board-approved, multi-center, case-control study. Patients admitted with a primary diagnosis of heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease were randomly selected for inclusion. Patients were excluded if they discharged against medical advice or expired during their index visit. Block randomization was utilized for equal representation of index diagnosis and site. Discharge medication regimen complexity index scores were compared between subjects with readmission versus those without. Medication regimen complexity index score was then used as a predictor in logistic regression modeling for readmission. Seven hundred and fifty-six patients were randomly selected for inclusion, and 101 (13.4%) readmitted within 30 days. The readmission group had higher medication regimen complexity index scores than the no-readmission group (p < 0.01). However, after controlling for demographics, disease state, length of stay, site, and medication count, medication regimen complexity index was no longer a significant predictor of readmission (odds ratio 0.99, 95% confidence interval 0.97-1.01) or revisit (odds ratio 0.99, 95% confidence interval 0.98-1.02). There is little evidence to support the use of medication regimen complexity index in readmission prediction when other measures are available. Medication regimen complexity index may lack sufficient sensitivity to capture an effect of medication

  5. Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Comparison of thallium scintigraphy with reinjection and PET imaging with sup 18 F-fluorodeoxyglucose

    SciTech Connect

    Bonow, R.O.; Dilsizian, V.; Cuocolo, A.; Bacharach, S.L. )

    1991-01-01

    In patients with chronic coronary artery disease and left ventricular dysfunction, the distinction between ventricular dysfunction arising from myocardial fibrosis and ischemic, but viable, myocardium has important clinical implications. By positron emission tomography (PET), enhanced fluorine-18-labeled fluorodeoxyglucose (FDG) uptake in myocardial segments with impaired function and reduced blood flow is evidence of myocardial viability. Reinjection of thallium-201 at rest immediately after stress-redistribution imaging may also provide evidence of myocardial viability by demonstrating thallium uptake in regions with apparently irreversible defects. To compare these two methods, we studied 16 patients with chronic coronary artery disease and left ventricular dysfunction, all of whom had irreversible defects on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT) imaging. Thallium was reinjected immediately after the redistribution study, and SPECT images were reacquired. The patients also underwent PET imaging with FDG and oxygen-15-labeled water. A total of 432 myocardial segments were analyzed from comparable transaxial tomograms, of which 166 (38%) had irreversible thallium defects on redistribution images before reinjection. FDG uptake was demonstrated in 121 (73%) of these irreversible defects. Irreversible defects were then subgrouped according to the degree of thallium activity, relative to peak activity in normal regions. Irreversible defects with only mild (60-85% of peak activity) or moderate (50-59% of peak) reduction in thallium activity were considered viable on the basis of FDG uptake in 91% and 84% of these segments, respectively. In contrast, in irreversible defects with severe reduction in thallium activity (less than 50% of peak), FDG uptake was present in 51% of segments.

  6. Effects of ranolazine on the exercise capacity of rats with chronic heart failure induced by myocardial infarction.

    PubMed

    Aaker, A; McCormack, J G; Hirai, T; Musch, T I

    1996-09-01

    Ranolazine was previously shown to stimulate cardiac glucose oxidation. Dichloroacetate (DCA) also does and was shown to improve exercise capacity in animals, but it has long-term toxicity problems. To test the hypothesis that ranolazine would increase exercise performance in the chronic heart failure (CHF) condition, we compared the exercise endurance capacities of rats with a surgically induced myocardial infarction (MI) with those of noninfarcted sham-operated (Sham) controls both before and after 14 and 28 days of drug administration. Chronic administration of ranolazine, 50 mg/kg twice daily (b.i.d.) oral, significantly reduced the endurance capacities of both Sham and MI rats (measured after a 12-h fast to reduce liver glycogen stores), as indicated by the reductions in run times to fatigue during a progressive treadmill test. Ranolazine produced reductions in resting plasma lactate and glucose concentrations of animals fasted for 12 h (consistent with stimulating glucose oxidation); however, tissue glycogen concentrations measured in various locomotor muscles located in the animal's hindlimb were unaffected when measured 48 h after the last treadmill test and after 12 h of fasting. Chronic administration of ranolazine did not increase the endurance capacity of rats with CHF induced by MI at the dosage and with the protocol used. To the contrary, the chronic administration of ranolazine appears to reduce the work capacity of all rats, suggesting that this drug may not be useful therapeutically in the treatment of CHF. Whether the decrements in endurance capacity produced by ranolazine are related to the high plasma concentrations of the drug produced in this study as compared with previous studies in humans remains subject to further experimentation.

  7. Acute Myocardial Infarction in the First Trimester of Pregnancy in a Great Grand Multiparous Woman with Poorly Controlled Chronic Hypertension

    PubMed Central

    Prasannan, Lakha; Blitz, Matthew J.; Rabin, Jill M.

    2016-01-01

    Introduction Acute myocardial infarction (MI) in pregnancy is a rare event, usually occurring late in gestation, either in the third trimester or in the puerperium. It is associated with significant maternal and fetal morbidity and mortality. Although diagnosis and management of MI in pregnancy has been discussed in the literature, management of pregnancy following an early antepartum MI, which may have more consequences for the fetus, has not received as much attention. Case A 38-year-old great grand multiparous woman presented to the emergency department complaining of acute onset chest pain. The patient had a history of chronic hypertension and was an active smoker. She was incidentally found to be 5 weeks pregnant. She was diagnosed with an acute MI, which was treated by primary percutaneous coronary intervention. Her subsequent pregnancy course was complicated by poorly controlled chronic hypertension, but she ultimately delivered a healthy newborn at 36 weeks of gestational age. Conclusion Good pregnancy outcomes are possible after early antepartum MI, especially with early diagnosis, appropriate treatment, and a multidisciplinary team approach to prenatal care. Delivery should occur in a tertiary referral center with experience managing high-risk obstetric patients with cardiac disease. PMID:27551581

  8. The Relationship Between Left Ventricular Fractional Shortening and Intravenous Administration of Stem Cells in Laboratory Rabbits Presenting Chronic Myocardial Infarction

    PubMed Central

    POP, IONEL CIPRIAN; GRAD, OVIDIU; PALL, EMOKE; PESTEAN, COSMIN; MIRCEAN, MIRCEA; MIRONIUC, ION AUREL

    2015-01-01

    Background and aims The present study conducted from March 2012 to July 2013 aimed to evaluate from echocardiographic point of view the effects of peripheral intravenous administration of mesenchymal stem cells (MSCs) in laboratory rabbits presenting 30 days old chronic myocardial infarction. Material and methods 30 days after the induction of an acute myocardial infarction in 40 laboratory rabbits by direct ligation of the left anterior descending coronary artery at about 10 mm from the apex, we injected 1×106 MSCs in the auricular vein in a group of 30 rabbits, and a group of 10 rabbits were used as controls. 30 days after the injection of stem cells the left ventricular (LV) fractional shortening (FS) was evaluated by echocardiography and compared with the control rabbits. Results In control rabbits, echocardiography revealed akinesis of apex, interventricular septum kinetics was also impaired, FS being approximately 6%. In 80% (24 rabbits) of the injected rabbits the FS of the LV was significantly greater than in the witness group (26+/−2%, p<0.0001). At 13.3% (4 rabbits) of the injected rabbits the FS of the LV showed no improvement in comparison with the control group (6.5+/−1%). Conclusion An improvement of LV SF 30 days after MSCs were injected(p<0.0001) was noted. We have to further determine if this improvement of the LV function is correlated with any histopathological changes and if it is not lost in time. Also, further studies needs to evaluate if there is any significant change in the overall mortality. PMID:26528044

  9. Extracellular volume fraction in coronary chronic total occlusion patients.

    PubMed

    Chen, Yin Yin; Zhang, Wei Guo; Yang, Shan; Yun, Hong; Deng, Sheng Ming; Fu, Cai Xia; Zeng, Meng Su; Jin, Hang; Guo, Liang

    2015-08-01

    (1) To assess extracellular volume fraction (ECV) and regional systolic function in patients presenting with coronary chronic total occlusion (CTO) in areas without significant late gadolinium enhancement (LGE), and (2) to investigate the correlation between angiography collateral flow and ECV in territories supplied by CTO vessels. A total of 50 angiographically documented CTO patients and 15 age- and sex-matched normal controls were recruited to the study. Myocardial ECV, was calculated in infarcted, global non-infarcted and the entire myocardium respectively. Segmental ECV was calculated from myocardial segments within the perfusion territory of a CTO vessel. The global and regional systolic function was evaluated using ejection fraction and percent systolic thickening. ECVs in global myocardium and global non-infarcted myocardium were significantly elevated in comparison with that in controls (29.1 ± 4.2% and 26.6 ± 2.6% vs. 23.3 ± 2.0%, all P < 0.005). Global ECV significantly correlated with LV ejection fraction (r = -0.56, P < 0.001) and ECV inversely correlated with systolic thickening in global non-infarcted myocardium (r = -0.31, P < 0.05). The lower segmental ECV was associated with the presence of well-developed collaterals (P = 0.004), and multivariate binary logistic analysis demonstrated that mean segmental ECV and course of disease were the independent discriminator of collateral flow with overall diagnostic accuracy of 74.4%. In patients with CTO, ECV is found to be increased beyond that observed with LGE, and correlates with LV regional wall motion abnormality, which appears to reflect diffuse myocardial fibrosis. Mean segmental ECV value, combined with course of disease, may serve as good predictors of collateral flow.

  10. Moderate ischemic mitral regurgitation after postero-lateral myocardial infarction in sheep alters left ventricular shear but not normal strain in the infarct and infarct borderzone

    PubMed Central

    Ge, Liang; Wu, Yife; Soleimani, Mehrdad; Khazalpour, Michael; Takaba, Kiyoaki; Tartibi, Mehrzad; Zhang, Zhihong; Acevedo-Bolton, Gabriel; Saloner, David A.; Wallace, Arthur W.; Mishra, Rakesh; Grossi, Eugene A.; Guccione, Julius M.; Ratcliffe, Mark B.

    2016-01-01

    Background Chronic ischemic mitral regurgitation (CIMR: MR) is associated with poor outcome. Left ventricular (LV) strain after postero-lateral myocardial infarction (MI) may drive LV remodeling. Although moderate CIMR has been previously shown to effect LV remodeling, the effect of CIMR on LV strain after postero-lateral MI remains unknown. We tested the hypothesis that moderate CIMR alters LV strain after postero-lateral MI. Methods/Results Postero-lateral MI was created in 10 sheep. Cardiac MRI with tags was performed 2 weeks before and 2, 8 and 16 weeks after MI. LV and right ventricular (RV) volumes were measured and regurgitant volume indexed to body surface area (BSA; RegurgVolume Index) calculated as the difference between LV and RV stroke volumes / BSA. Three-dimensional strain was calculated. Circumferential (Ecc)and longitudinal (Ell) strains were reduced in the infarct proper, MI borderzone (BZ) and remote myocardium 16 weeks after MI. In addition, radial circumferential (Erc) and radial longitudinal (Erl) shear strains were reduced in remote myocardium but increased in the infarct and BZ 16 weeks after MI. Of all strain components, however, only Erc was effected by RegurgVolume Index (p=0.0005). There was no statistically significant effect of RegurgVolume Index on Ecc, Ell, Erl, or circumferential longitudinal shear strain (Ecl). Conclusions Moderate CIMR alters radial circumferential shear strain after postero-lateral MI in the sheep. Further studies are needed to determine the effect of shear strain on myocyte hypertrophy and the effect of mitral repair on myocardial strain. PMID:26857634

  11. Tissue engineering for post-myocardial infarction ventricular remodeling.

    PubMed

    Kolettis, T M; Vilaeti, A; Dimos, K; Tsitou, N; Agathopoulos, S

    2011-03-01

    Myocardial tissue engineering involves the design of biomaterial scaffolds, aiming at regenerating necrotic myocardium after myocardial infarction. Biomaterials provide mechanical support to the infarct area and they can be used as vehicles for sustained and controlled local administration of cells and growth factors. Although promising results have been reported in experimental studies, many issues need to be addressed before human use.

  12. Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction.

    PubMed

    Hardwick, Jean C; Ryan, Shannon E; Beaumont, Eric; Ardell, Jeffrey L; Southerland, E Marie

    2014-04-01

    Myocardial infarction (MI) is associated with remodeling of the heart and neurohumoral control systems. The objective of this study was to define time-dependent changes in intrinsic cardiac (IC) neuronal excitability, synaptic efficacy, and neurochemical modulation following MI. MI was produced in guinea pigs by ligation of the coronary artery and associated vein on the dorsal surface of the heart. Animals were recovered for 4, 7, 14, or 50 days. Intracellular voltage recordings were obtained in whole mounts of the cardiac neuronal plexus to determine passive and active neuronal properties of IC neurons. Immunohistochemical analysis demonstrated an immediate and persistent increase in the percentage of IC neurons immunoreactive for neuronal nitric oxide synthase. Examination of individual neuronal properties demonstrated that after hyperpolarizing potentials were significantly decreased in both amplitude and time course of recovery at 7 days post-MI. These parameters returned to control values by 50 days post-MI. Synaptic efficacy, as determined by the stimulation of axonal inputs, was enhanced at 7 days post-MI only. Neuronal excitability in absence of agonist challenge was unchanged following MI. Norepinephrine increased IC excitability to intracellular current injections, a response that was augmented post-MI. Angiotensin II potentiation of norepinephrine and bethanechol-induced excitability, evident in controls, was abolished post-MI. This study demonstrates that MI induces both persistent and transient changes in IC neuronal functions immediately following injury. Alterations in the IC neuronal network, which persist for weeks after the initial insult, may lead to alterations in autonomic signaling and cardiac control.

  13. Evaluation of structural remodeling of the atria with OCT in a chronic rat model of myocardial infarction (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Eberle, Melissa M.; Thorn, Stephanie; Young, Lawerence; Pfau, Daniel; Madwed, Jeffrey; Small, Kersten; Kilmas, Michael; Choma, Michael A.; Sinusas, Albert J.

    2017-02-01

    Atrial fibrillation (AF) occurs following myocardial infarction (MI) and is associated with left ventricular dysfunction, which promotes the development of atrial remodeling and permanent atrial fibrosis. The purpose of this study was determining the effects of MI on left atrial (LA) remodeling with and without therapy with an angiotensin converting enzyme inhibition (ACEi) utilizing optical coherence tomography (OCT). As the composition of the myocardial tissue changes during LA remodeling the optical attenuation of the light will also change providing a metric to quantify the structural remodeling process. Lewis rats (240-275 g) underwent either surgical ligation of left coronary artery creating chronic MI, or SHAM surgery. 13 weeks post-surgery, ex vivo OCT imaging was performed of the LA appendage. Depth-resolved, attenuation coefficient volumes were calculated and the resulting atrial wall attenuation values were analyzed for four experimental groups: SHAM, SHAM with ACEi, MI no ACEi, and MI with ACEi. Quantification of tissue attenuation was performed and shown to significantly increase with MI in association with increases in collagen as verified with corresponding histological sectioning. Fractal analysis of the LA wall trabeculation patterns, 100 µm below the surface, was performed to quantify wall thickening associated with LA remodeling. A significant increase in fractal dimension was determined post MI compared to SHAM corresponding to a loss of the trabeculation pattern and wall thickening. The results from this study demonstrate OCT as an imaging technique capable of investigate LA remodeling with high resolution and label-free optical contrast processing.

  14. Chronic Kidney Disease and Subclinical Brain Infarction Increase the Risk of Vascular Cognitive Impairment: The Sefuri Study.

    PubMed

    Yao, Hiroshi; Araki, Yuko; Takashima, Yuki; Uchino, Akira; Yuzuriha, Takefumi; Hashimoto, Manabu

    2017-02-01

    The purpose of this study was to determine the complex associations among chronic kidney disease (CKD), subclinical brain infarction (SBI), and cognitive impairment. We used structural equation modeling (SEM) to examine the complex relationships among CKD, SBI, and cognitive function with Mini-Mental State Examination (MMSE; global function) and modified Stroop test (executive function) in a population-based cohort of 560 non-demented elderly subjects. Path analysis based on SEM revealed that the direct paths from estimated glomerular filtration rate (eGFR) to SBI and from SBI to executive function were significant (β = -.10, P = .027, and β = .16, P < .001, respectively). Furthermore, the direct path from eGFR to executive function was also significant (β = -.12, P = .006), indicating that the effects of CKD on executive function are independent of SBI. The direct paths from age and education to global cognitive function were highly significant (β = -.17 and .22, respectively, P < .001), whereas the direct path from eGFR to MMSE was not significant. Our findings indicate that CKD confers a risk of vascular cognitive impairment or executive dysfunction through mechanisms dependent and independent of SBI. Treating CKD may be a potential strategy to protect against vascular cognitive impairment or executive dysfunction in healthy elderly subjects. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Major depressive disorder in chronic heart failure patients: Does silent cerebral infarction cause major depressive disorder in this patient population?

    PubMed

    Kozdağ, Güliz; Yaluğ, İrem; İnan, Nagihan; Ertaş, Gökhan; Selekler, Macit; Kutlu, Hüseyin; Kutlu, Ayşe; Emre, Ender; Çetin, Metin; Ural, Dilek

    2015-09-01

    Depression frequently occurs in patients with heart failure as similar pathophysiological mechanisms present in both these diseases. Patients with dilated cardiomyopathy (DCM) have a high incidence of clinically asymptomatic silent cerebral infarction (SCI). This study aimed to evaluate the relation between SCI and major depressive disorder (MDD), and between MDD and clinical and biochemical parameters in DCM patients. Patients with ischemic and non-ischemic DCM who had chronic heart failure (CHF) (39 male, 10 female, age 60±10 years) were included in the study. Mean patient ejection fraction (EF) was 34±10%. Patients had no localized neurological symptoms or stroke history. The etiology of DCM was ischemic in 40 and non-ischemic in 9 patients. Twenty-five age-matched healthy volunteers served as a control group for comparison of SCI and MDD prevalence. Patients had mild to severe CHF symptoms. Prevalence of SCI and MDD was significantly higher in patients with DCM than in the control group; 63% vs 8%; p<0.001, and 52% vs 20%; p<0.001 respectively. Patients with SCI had a higher prevalence of MDD than patients without SCI in DCM (61% vs 27%, p=0.02). CHF patients have an increased prevalence of SCI and MDD. Patients with SCI have a higher prevalence of MDD compared to patients without SCI in CHF.

  16. Quantitative T2 mapping for detecting myocardial edema after reperfusion of myocardial infarction: validation and comparison with T2-weighted images.

    PubMed

    Park, Chul Hwan; Choi, Eui-Young; Kwon, Hyuck Moon; Hong, Bum Kee; Lee, Byoung Kwon; Yoon, Young Won; Min, Pil-Ki; Greiser, Andreas; Paek, Mun Young; Yu, Wei; Sung, Yon Mi; Hwang, Sung Ho; Hong, Yoo Jin; Kim, Tae Hoon

    2013-06-01

    This study evaluates the clinical usefulness of T2 mapping for the detection of myocardial edema in the re-perfused acute myocardial infarction (MI). Cardiac MRIs were reviewed in 20 patients who had acute MI after reperfusion therapy. The regional T2 values and T2-weighted image (T2WI) signal intensities (SI) were measured in the infarcted and remote zones of the myocardium. Patients were divided into three groups according to the signal patterns of the infarcted myocardium on the T2WIs. The T2 values of the infarcted zones were compared on the T2 maps among the three groups. Validation of the T2 values was performed in the normal myocardium of seven healthy volunteers. There were no significant differences in mean T2WI-SI or T2 values in the normal myocardium of healthy volunteers compared to the remote myocardium of acute MI patients (p > 0.05). Mean SI on the T2WIs was significantly higher in the infarcted myocardium (81.3 ± 37.6) than in the remote myocardium (63.8 ± 18.1) (p < 0.05). The T2WIs showed high SI in ten patients (group 1), iso-SI in seven (group 2), and low SI in three (group 3) in the infarcted myocardium, compared to the remote myocardium. The T2 maps showed that T2 values in the infarcted myocardium had mostly increased, regardless of group, with values of 71 ± 9 ms in group 1, 64.9 ± 7.4 ms in group 2, and 61.4 ± 8.5 ms in group 3. T2 mapping is superior to T2WI for detecting areas of high SI in the infarcted myocardium. Therefore, quantitative T2 mapping sequences may be more useful and reliable in identifying myocardial edema in the infarcted myocardium than T2WI.

  17. The pathophysiologic process of ventricular remodeling: from infarct to failure.

    PubMed

    Paul, S

    1995-05-01

    In the past, hypertensive heart disease was the principal cause of congestive heart failure, but currently ischemic heart disease is the major etiologic factor. In the last 20 years, the role of myocardial infarction (MI) and the subsequent alteration in ventricular architecture of the infarcted and noninfarcted myocardium have become increasingly associated with a phenomenon known as ventricular remodelling. This process consists of left ventricular wall thinning in the infarction area, ventricular chamber dilatation, and compensatory hypertrophy of the noninfarcted portion of the myocardium. This article describes the pathophysiologic transformation that begins with MI and ventricular remodeling and ends in congestive heart failure.

  18. Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium.

    PubMed

    Huang, Jing; Zhang, Zhiping; Guo, Jian; Ni, Aiguo; Deb, Arjun; Zhang, Lunan; Mirotsou, Maria; Pratt, Richard E; Dzau, Victor J

    2010-06-11

    Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly because of poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (eg, CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs 3 days postmyocardial infarction (MI). CCR1-MSC-injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium 3 days after MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks after MI. Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium.

  19. Infarct density distribution by MRI in the porcine model of acute and chronic myocardial infarction as a potential method transferable to the clinic.

    PubMed

    Varga-Szemes, Akos; Simor, Tamas; Lenkey, Zsofia; van der Geest, Rob J; Kirschner, Robert; Toth, Levente; Brott, Brigitta C; Elgavish, Ada; Elgavish, Gabriel A

    2014-06-01

    To study the feasibility of a myocardial infarct (MI) quantification method [signal intensity-based percent infarct mapping (SI-PIM)] that is able to evaluate not only the size, but also the density distribution of the MI. In 14 male swine, MI was generated by 90 min of closed-chest balloon occlusion followed by reperfusion. Seven (n = 7) or 56 (n = 7) days after reperfusion, Gd-DTPA-bolus and continuous-infusion enhanced late gadolinium enhancement (LGE) MRI, and R1-mapping were carried out and post mortem triphenyl-tetrazolium-chloride (TTC) staining was performed. MI was quantified using binary [2 or 5 standard deviation (SD)], SI-PIM and R1-PIM methods. Infarct fraction (IF), and infarct-involved voxel fraction (IIVF) were determined by each MRI method. Bias of each method was compared to the TTC technique. The accuracy of MI quantification did not depend on the method of contrast administration or the age of the MI. IFs obtained by either of the two PIM methods were statistically not different from the IFs derived from the TTC measurements at either MI age. IFs obtained from the binary 2SD method overestimated IF obtained from TTC. IIVF among the three different PIM methods did not vary, but with the binary methods the IIVF gradually decreased with increasing the threshold limit. The advantage of SI-PIM over the conventional binary method is the ability to represent not only IF but also the density distribution of the MI. Since the SI-PIM methods are based on a single LGE acquisition, the bolus-data-based SI-PIM method can effortlessly be incorporated into the clinical image post-processing procedure.

  20. Risk Factors for Development of Chronic Kidney Disease following Renal Infarction: Retrospective Evaluation of Emergency Room Patients from a Single Center

    PubMed Central

    Lin, Wen-Ling; Seak, Chen-June; Wu, Jiunn-Yih; Weng, Yi-Ming; Chen, Hang-Cheng

    2014-01-01

    Background Previous studies have analyzed factors associated with renal infarction so that patients can be provided with earlier diagnosis and treatment. However, the factors associated with development of chronic kidney disease (CKD) following renal infarction are unknown. Methods We retrospectively reviewed the records of patients with a diagnosis of renal infarction based on enhanced computed tomography. All patients were admitted to a single emergency department in Taiwan from 1999 to 2008. Univariate and multivariate analysis were used to assess the effect of different factors on development of CKD based on estimates of the glomerular filtration rate (eGFR) at admission and at 3–12 months after discharge. Results Univariate analysis indicated significantly increased risk of CKD in patients older than 50 years, with symptoms for 24 h or less before admission, lower eGFR at admission, APACHE II score greater than 7, SOFA score greater than 1, ASA score greater than 2, and SAPS II score greater than 15. Multivariate analysis indicated that only SOFA score greater than 1 was significantly and independently associated with CKD at follow-up (p<0.001). Conclusions A total of 32.5% of patients admitted for renal infarction over a ten-year period developed CKD at 3–12 months after discharge. A SOFA score greater than 1 was significantly and independently associated with development of CKD in these patients. PMID:24911965

  1. Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction.

    PubMed

    Liu, XinHua; Pan, LiLong; Gong, QiHai; Zhu, YiZhun

    2010-12-15

    Leonurine, an alkaloid typically found in Herba leonuri, is known to have both antioxidant and cardioprotective properties. In the present study, we investigated the cardioprotective mechanism of leonurine the in vivo rat model of chronic myocardial ischemia and in vitro H9c2 cardiac myocyte model of oxidative stress. Myocardial ischemia was induced by ligating the left anterior descending coronary artery. Rats were divided into sham, myocardial ischemia+saline, and myocardial ischemia+leonurine (15 mg/kg/day). Cardiac function was recorded by catheterization. Apoptosis-related factor vascular endothelial growth factor (VEGF), survivin, Bcl-2 and Bax and pro-survival signaling pathways Akt, hypoxia inducible factor (HIF)-1α were measured by Western blotting or RT-PCR. Our results showed leonurine significantly improved myocardial function as evidenced by the decreased left ventricle end-diastolic pressure and the increased +dP/dt. Interestingly, leonurine increased the phosphorylation of Akt, the protein and gene expression of Bcl-2, but it reduced the protein and gene expression of Bax in vivo. Meanwhile leonurine significantly increased Akt phosphorylation in a concentration-dependent manner in H9c2 cardiac myocyte induced by oxidative stress in vitro, which was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. Furthermore, leonurine not only increased the expression of HIF-1α but also the expression of survivin and VEGF. The results of present study demonstrated, for the first time that leonurine has potent anti-apoptotic effects after chronic myocardial ischemia mediated by activating the PI3K/Akt signaling pathway. Angiogenic mechanisms may be partially responsible for such an effect, which needs to be studied further.

  2. Scale-selective analysis of myocardium polarization images in problems of diagnostic of necrotic changes

    NASA Astrophysics Data System (ADS)

    Ushenko, O. G.; Dubolazov, O. V.; Ushenko, Yu. O.; Gorsky, M. P.

    2015-11-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  3. Statistical and fractal analysis of autofluorescent myocardium images in posthumous diagnostics of acute coronary insufficiency

    NASA Astrophysics Data System (ADS)

    Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Garazdiuk, M.; Motrich, A. V.

    2014-08-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  4. The Adult Göttingen Minipig as a Model for Chronic Heart Failure After Myocardial Infarction: Focus on Cardiovascular Imaging and Regenerative Therapies

    PubMed Central

    Schuleri, Karl H; Boyle, Andrew J; Centola, Marco; Amado, Luciano C; Evers, Robert; Zimmet, Jeffrey M; Evers, Kristine S; Ostbye, Katherine M; Scorpio, Diana G; Hare, Joshua M; Lardo, Albert C

    2008-01-01

    Porcine models have become increasingly popular in cardiovascular research. The standard farm pig rapidly increases in body weight and size, potentially confounding serial measurements of cardiac function and morphology. We developed an adult porcine model that does not show physiologic increases in heart mass during the study period and is suitable for long-term study. We compared adult minipigs with the commonly used adolescent Yorkshire swine. Myocardial infarction was induced in adult Göttingen minipigs and adolescent Yorkshire swine by occlusion of the left anterior descending coronary artery followed by reperfusion. At 8 wk after infarction, the left ventricular ejection fraction was 34.1 ± 2.3% in minipigs and 30.7 ± 2.0% in Yorkshire swine. The left ventricular end-diastolic mass in Yorkshire pigs assessed by magnetic resonance imaging increased 17 ± 5 g, from 42.6 ± 4.3 g at week 1 after infarction to 52.8 ± 6.6 g at week 8, whereas it remained unchanged in minipigs. Cardiac anatomy and physiology in adult minipigs were evaluated invasively by angiography and noninvasively by Multidetector Computed Tomography and by Magnetic Resonance Imaging at 1.5 T and 3 T prior to myocardial infarction and during folow-up. This porcine heart failure model is reproducible, mimics the pathophysiology in patients who have experienced myocardial infarction, and is suitable for imaging studies. New heart failure therapies and devices can be tested preclinically in this adult animal model of chronic heart failure. PMID:19149414

  5. Incidence and clinical impact of concurrent chronic total occlusion according to gender in ST-elevation myocardial infarction.

    PubMed

    Bataille, Yoann; Déry, Jean-Pierre; Larose, Éric; Abdelaal, Eltigani; Machaalany, Jimmy; Rodés-Cabau, Josep; Rinfret, Stéphane; Déry, Ugo; Costerousse, Olivier; Roy, Louis; Bertrand, Olivier F

    2013-07-01

    To determine the prevalence of a concurrent CTO in men and women and to examine its impact on mortality. The impact of chronic total occlusion (CTO) in patients with ST-elevation myocardial infarction (STEMI) according to gender has not been assessed. Patients referred with STEMI were categorized into single vessel disease (SVD), multivessel disease (MVD) without, with 1 or > 1 CTO. The primary end-point was the 1-year mortality. Among the 2020 STEMI patients included between 2006 and 2011, 24% were female. Women were older, had more hypertension and renal failure (P < 0.0001 for all). The prevalence of 1 or > 1 concurrent CTO was similar in both sexes, 7 and 1%, respectively. Early and late mortality was significantly higher in women compared with men (P < 0.0001). In women, the mortality was significantly worse in patients with > 1 CTO (100%) and with 1 CTO (36.4%) compared with those with MVD without CTO (18.4%) or with SVD (10.4%) (P < 0.0001). MVD with and without concurrent CTO were both independent predictors of 1-year mortality in women (HR 3.58; 95 % CI 1.69-7.18 and HR 2.76; 95 % CI 1.33-5.51) whereas only MVD with CTO was predictive in men (HR 2.19; 95% CI 1.20-3.97). Among unselected STEMI patients, the prevalence of CTO was equal in both sexes whereas early and late mortality remained significantly higher in women. Other factors than the presence of a concurrent CTO must be explored to explain differences in survival after STEMI between women and men. Copyright © 2013 Wiley Periodicals, Inc.

  6. Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study

    PubMed Central

    Mehta, Nehal N.; Matthews, Gregory J.; Krishnamoorthy, Parasuram; Shah, Rhia; McLaughlin, Catherine; Patel, Parth; Budoff, Matthew; Chen, Jing; Wolman, Melanie; Go, Alan; He, Jiang; Kanetsky, Peter A.; Master, Stephen R.; Rader, Daniel J.; Raj, Dominic; Gadegbeku, Crystal A.; Shah, Rachana; Schreiber, Marty; Fischer, Michael J.; Townsend, Raymond R.; Kusek, John; Feldman, Harold I.; Foulkes, Andrea S.; Reilly, Muredach P.; Appel, Lawrence J.; Feldman, Harold I.; Go, Alan S.; He, Jiang; Kusek, John W.; Lash, James P.; Ojo, Akinlolu; Rahman, Mahboob; Townsend, Raymond R.

    2014-01-01

    Aims Genome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown. Methods and results We analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate (eGFR), and higher inflammatory cytokine levels (P < 0.05). In fully adjusted models, higher study-entry CXCL12 was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence interval 1.14, 1.33, P < 0.001) for one standard deviation (SD) increase in CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI (1.26; 1.09,1.45, P < 0.001), death (1.20; 1.09,1.33, P < 0.001), and combined MI/death (1.23; 1.13–1.34, P < 0.001) adjusting for demographic factors, known CVD risk factors, and inflammatory markers and remained significant for MI (1.19; 1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after further controlling for eGFR and urinary albumin:creatinine ratio. Conclusions In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials. PMID:24306482

  7. Comparison of thrombolysis in myocardial infarction, Global Registry of Acute Coronary Events, and Acute Physiology and Chronic Health Evaluation II risk scores in patients with acute myocardial infarction who require mechanical ventilation for more than 24 hours.

    PubMed

    Eran, Oren; Novack, Victor; Gilutz, Harel; Zahger, Doron

    2011-02-01

    The ability to provide an accurate prognosis in an intensive care unit is of major importance. Numerous risk scores have been developed to predict hospital mortality based on demographic, physiologic, and clinical data. These scores were universally developed in general medical or surgical intensive care units. Patients admitted to a cardiac care unit differ in many aspects from those admitted to general medical intensive care units. Few patients require mechanical ventilation and prolonged intensive care. Performance of risk scores developed for patients with acute myocardial infarction (AMI) in this subgroup is unknown. We prospectively studied 51 consecutive patients who were admitted to a cardiac care unit from September 2006 to March 2008 for AMI and received mechanical ventilation for >24 hours. Acute Physiology and Chronic Health Evaluation II (APACHE II), Thrombolysis In Myocardial Infarction, and Global Registry of Acute Coronary Events risk scores were calculated for each patient. Mortality rates were extrapolated based on these 3 risk scores. Twenty-two of 51 patients (43%) died in hospital. Age, mean arterial pressure, urea, albumin, hemoglobin, need for vasopressors, and estimated glomerular filtration rate were predictive of mortality. APACHE II and Global Registry of Acute Coronary Events scores were higher in nonsurvivors but Thrombolysis In Myocardial Infarction risk score was not predictive of mortality. APACHE II score had the highest value for area under receiver operator characteristics curve for mortality prediction. In conclusion, patients with AMI requiring mechanical ventilation have a high mortality rate. This risk is predicted by co-morbidities better than by direct cardiac parameters. Consequently, conventional AMI risk scores do not perform well in this very sick population and the APACHE II score better predicts their short-term outcome.

  8. Inhibition of anti-apoptotic signals by Wortmannin induces apoptosis in the remote myocardium after LAD ligation: evidence for a protein kinase C-δ-dependent pathway.

    PubMed

    Wiedemann, Stephan; Wessela, Teresa; Schwarz, Kerstin; Joachim, Dirk; Jercke, Marcel; Strasser, Ruth H; Ebner, Bernd; Simonis, Gregor

    2013-01-01

    It has been shown that, in the remote myocardium after infarction (MI), protein kinase C (PKC) inhibition reduces apoptosis both by blocking proapoptotic pathways and by activating antiapoptotic signals including the Akt pathway. However, it was open if vice versa, blockade of antiapoptotic pathways may influence proapoptotic signals. To clarify this, the present study tested the effects of the PI3-kinase blocker Wortmannin on proapoptotic signals and on apoptosis execution in the remote myocardium after infarction. Rats were subjected to MI by LAD ligation in situ. Some were pre-treated with Wortmannin alone or in combination with the PKC inhibitor Chelerythrine. After 24 h, pro- and anti-apoptotic signals (caspase-3, PKC isoforms, p38-MAPK, p42/44-MAPK, Akt, Bad), and marker of apoptosis execution (TUNEL) were quantified in the myocardium remote from the infarction. Wortmannin treatment increased apoptosis in the remote myocardium both at baseline and after MI, together with an activation of the PKC-δ/p38-MAPK-pathway. PKC-ε and p42/44-MAPK were unaffected. Combined treatment with Wortmannin and Chelerythrine fully reversed the pro-apoptotic effects of Wortmannin both at baseline and after MI. The PKC-δ-p38-MAPK-pathway as a strong signal for apoptosis in the non-infarcted myocardium can be influenced by targeting the anti-apoptotic PI3-kinase pathway. This gives evidence of a bi-directional crosstalk of pro- and anti-apoptotic signals after infarction.

  9. A Case of Apoplexy Attack-Like Neuropathy due to Hereditary Neuropathy with Liability to Pressure Palsies in a Patient Diagnosed with Chronic Cerebral Infarction.

    PubMed

    Hachisuka, Akiko; Matsushima, Yasuyuki; Hachisuka, Kenji; Saeki, Satoru

    2016-06-01

    Hereditary neuropathy with liability to pressure palsies is an inherited disease associated with the loss of a copy of the PMP22 gene. The condition leads to mononeuropathy due to compression and easy strangulation during daily life activities, resulting in sudden muscle weakness and sensory disturbance, and displaying symptoms similar to cerebrovascular diseases. We report the case of an 80-year-old man with left paralysis due to chronic cerebral infarction. His medical history indicated remarkable recovery from about 4 months after the onset of left hemiplegia with predominant involvement of the fingers. Despite subsequent recurrent monoplegia of the upper or lower limbs, brain magnetic resonance imaging consistently revealed only previous cerebral infarction in the right corona radiata without new lesions. Medical examination showed reduced deep tendon reflexes in his extremities on both the healthy and hemiplegic sides. Nerve conduction studies showed delayed conduction at the bilateral carpal and cubital tunnels and near the right caput fibulae. Genetic analysis revealed loss of a copy of the PMP22 gene. Thus, he was diagnosed with a cerebral infarction complicated by hereditary neuropathy with liability to pressure palsies. Stroke patients develop sudden muscle weakness and sensory disturbance. However, if such patients have no hyperactive deep tendon reflexes and show atypical recovery of paralysis that does not correspond to findings of imaging modalities, nerve conduction studies and genetic analysis may be necessary, considering the complication of hereditary neuropathy with liability to pressure palsies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Early-phase myocardial infarction: Evaluation by MR imaging

    SciTech Connect

    Tscholakoff, D.; Higgins, C.B.; McNamara, M.T.; Derugin, N.

    1986-06-01

    In vivo gated magnetic resonance (MR) imaging was performed in 12 dogs immediately after occlusion of the left anterior descending coronary artery and serially up to 5 hours and again between 4 and 14 days. This was done to evaluate the appearance of acute myocardial infarcts and to determine how soon after coronary artery occlusion MR imaging can demonstrate the site of acute myocardial ischemia. In nine dogs with postmortem evidence of myocardial infarction, regional increase of signal intensity of the myocardium was present by 3 hours after coronary occlusion and conformed to the site of myocardial infarct found at autopsy. The signal intensity on T2-weighted images of the infarcted on T2-weighted images of the infarcted myocardium was significantly greater than that of normal myocardium at 3, 4, and 5 hours after occlusion. The T2 (spin-spin) relaxation time was significantly prolonged in the region of myocardial infarct at 3, 4, and 5 hours post-occlusion compared with normal myocardium. Myocardial wall thinning and increased intracavitary flow signal were found in six dogs with comparable pre- and postocclusion images in late systole.

  11. Delayed, oral pharmacological inhibition of calpains attenuates adverse post-infarction remodelling.

    PubMed

    Poncelas, Marcos; Inserte, Javier; Aluja, David; Hernando, Victor; Vilardosa, Ursula; Garcia-Dorado, David

    2017-07-01

    Calpains activate during myocardial ischemia-reperfusion and contribute to reperfusion injury. Studies in transgenic animals with altered calpain/calpastatin system subjected to permanent ischemia suggest that calpains are also involved in post-infarction remodelling and heart failure. To determine whether delayed oral administration of the calpain inhibitor SNJ-1945 reduces adverse myocardial remodelling and dysfunction following transient coronary occlusion. Male Sprague-Dawley rats were subjected to 30 min of ischemia followed by 21 days of reperfusion and received the calpain inhibitor SNJ-1945 intraperitoneally at the onset of reperfusion (Acute group), orally starting after 24 h of reperfusion and for 14 days (Chronic group), or the combination of both treatments. Calpain-1 and calpain-2 protein content increased and correlated with higher calpain activity in control hearts. Administration of SNJ-1945 attenuated calpain activation, and reduced scar expansion, ventricular dilation and dysfunction in both acute and chronic groups. Acute treatment reduced infarct size in hearts reperfused for 24 h and inflammation measured after 3 days. Delayed, chronic oral administration of SNJ-1945 attenuated inflammation, cardiomyocyte hypertrophy and collagen infiltration in the non-infarcted myocardium at 21 days in correlation with increased levels of IĸB and reduced NF-ĸB activation. In cultured fibroblasts, SNJ-1945 attenuated TGF-β1-induced fibroblast activation. Our data demonstrate for the first time that long-term calpain inhibition is possible with delayed oral treatment, attenuates adverse post-infarction remodelling, likely through prevention of NF-ĸB activation, and may be a promising therapeutic intervention to prevent adverse remodelling and heart failure in patients with acute myocardial infarction.

  12. Proliferation and recruitment contribute to myocardial macrophage expansion in chronic heart failure

    PubMed Central

    Sager, Hendrik B.; Hulsmans, Maarten; Lavine, Kory J.; Moreira, Marina B.; Heidt, Timo; Courties, Gabriel; Sun, Yuan; Iwamoto, Yoshiko; Tricot, Benoit; Khan, Omar F.; Dahlman, James E.; Borodovsky, Anna; Fitzgerald, Kevin; Anderson, Daniel G.; Weissleder, Ralph; Libby, Peter; Swirski, Filip K.; Nahrendorf, Matthias

    2017-01-01

    Rationale Macrophages reside in the healthy myocardium, participate in ischemic heart disease and modulate myocardial infarction (MI) healing. Their origin and roles in post-MI remodeling of non-ischemic remote myocardium, however, remain unclear. Objective This study investigated the number, origin, phenotype and function of remote cardiac macrophages residing in the non-ischemic myocardium in mice with chronic heart failure after coronary ligation. Methods and Results Eight weeks post-MI, fate mapping and flow cytometry revealed that a 2.9-fold increase in remote macrophages results from both increased local macrophage proliferation and monocyte recruitment. Heart failure produced by extensive MI, through activation of the sympathetic nervous system, expanded medullary and extramedullary hematopoiesis. Circulating Ly6Chigh monocytes rose from 64±5 to 108±9 /μl blood (p<0.05). Cardiac monocyte recruitment declined in Ccr2−/− mice, reducing macrophage numbers in the failing myocardium. Mechanical strain of primary murine and human macrophage cultures promoted cell cycle entry, suggesting that the increased wall tension in post-MI heart failure stimulates local macrophage proliferation. Strained cells activated the MAPK pathway, while specific inhibitors of this pathway reduced macrophage proliferation in strained cell cultures and in the failing myocardium (p<0.05). Steady-state cardiac macrophages, monocyte-derived and locally sourced macrophages isolated from failing myocardium expressed different genes in a pattern distinct from the M1/M2 macrophage polarization paradigm. In vivo silencing of endothelial cell adhesion molecules curbed post-MI monocyte recruitment to the remote myocardium and preserved ejection fraction (27.4±2.4 vs.19.1±2%, p<0.05). Conclusions Myocardial failure is influenced by an altered myeloid cell repertoire. PMID:27444755

  13. Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failure.

    PubMed

    Sager, Hendrik B; Hulsmans, Maarten; Lavine, Kory J; Moreira, Marina B; Heidt, Timo; Courties, Gabriel; Sun, Yuan; Iwamoto, Yoshiko; Tricot, Benoit; Khan, Omar F; Dahlman, James E; Borodovsky, Anna; Fitzgerald, Kevin; Anderson, Daniel G; Weissleder, Ralph; Libby, Peter; Swirski, Filip K; Nahrendorf, Matthias

    2016-09-16

    Macrophages reside in the healthy myocardium, participate in ischemic heart disease, and modulate myocardial infarction (MI) healing. Their origin and roles in post-MI remodeling of nonischemic remote myocardium, however, remain unclear. This study investigated the number, origin, phenotype, and function of remote cardiac macrophages residing in the nonischemic myocardium in mice with chronic heart failure after coronary ligation. Eight weeks post MI, fate mapping and flow cytometry revealed that a 2.9-fold increase in remote macrophages results from both increased local macrophage proliferation and monocyte recruitment. Heart failure produced by extensive MI, through activation of the sympathetic nervous system, expanded medullary and extramedullary hematopoiesis. Circulating Ly6C(high) monocytes rose from 64±5 to 108±9 per microliter of blood (P<0.05). Cardiac monocyte recruitment declined in Ccr2(-/-) mice, reducing macrophage numbers in the failing myocardium. Mechanical strain of primary murine and human macrophage cultures promoted cell cycle entry, suggesting that the increased wall tension in post-MI heart failure stimulates local macrophage proliferation. Strained cells activated the mitogen-activated protein kinase pathway, whereas specific inhibitors of this pathway reduced macrophage proliferation in strained cell cultures and in the failing myocardium (P<0.05). Steady-state cardiac macrophages, monocyte-derived macrophages, and locally sourced macrophages isolated from failing myocardium expressed different genes in a pattern distinct from the M1/M2 macrophage polarization paradigm. In vivo silencing of endothelial cell adhesion molecules curbed post-MI monocyte recruitment to the remote myocardium and preserved ejection fraction (27.4±2.4 versus 19.1±2%; P<0.05). Myocardial failure is influenced by an altered myeloid cell repertoire. © 2016 American Heart Association, Inc.

  14. Impact of Denervated Myocardium on Improving Risk Stratification for Sudden Cardiac Death

    PubMed Central

    Cain, Michael E.

    2014-01-01

    Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to 70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We tested whether hibernating myocardium or myocardial sympathetic denervation identifies patients at high-risk for developing VT/VF independently of ejection fraction (EF). Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation (11C-meta-hydroxyephedrine [11C-HED]), perfusion (13N-ammonia), and viability (insulin-stimulated 18F-2-deoxyglucose [18FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a primary prevention implantable cardioverter defibrillator (ICD). The primary end-point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable denervated myocardium (11C-HED-18FDG mismatch, P = .03) predicted SCA, whereas hibernating and infarcted myocardium did not. Multivariate analysis identified four independent predictors of SCA: denervated myocardium > 37.6% of left ventricule (LV), LV end-diastolic volume > 98 mL/m2, creatinine level > 1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated myocardium quantified using PET strongly predicts risk of SCA, and is independent of EF, infarct volume, and other clinical variables. PMID:25125727

  15. Impact of denervated myocardium on improving risk stratification for sudden cardiac death.

    PubMed

    Cain, Michael E

    2014-01-01

    Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to 70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We tested whether hibernating myocardium or myocardial sympathetic denervation identifies patients at high-risk for developing VT/VF independently of ejection fraction (EF). Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia), and viability (insulin-stimulated (18)F-2-deoxyglucose [(18)FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a primary prevention implantable cardioverter defibrillator (ICD). The primary end-point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable denervated myocardium ((11)C-HED-(18)FDG mismatch, P = .03) predicted SCA, whereas hibernating and infarcted myocardium did not. Multivariate analysis identified four independent predictors of SCA: denervated myocardium > 37.6% of left ventricule (LV), LV end-diastolic volume > 98 mL/m(2), creatinine level > 1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated myocardium quantified using PET strongly predicts risk of SCA, and is independent of EF, infarct volume, and other clinical variables.

  16. The role of chemokines in mesenchymal stem cell homing to myocardium.

    PubMed

    Wu, Yaojiong; Zhao, Robert C H

    2012-03-01

    A growing body of preclinical evidence suggests that mesenchymal stem cells (MSCs) are effective for the structural and functional recovery of the infracted heart. Accordingly, clinical trials are underway to determine the benefit of MSC-based therapies. While systemic administration of MSCs is an attractive strategy, and is the route currently used for the administration of MSCs in clinical studies for myocardial infarction, the majority of infused cells do not appear to localize to infracted myocardium in animal studies. Recently, important progress has been made in identifying chemokine receptors critical for the migration and homing of MSCs. Here, we review recent literature regarding mechanisms of MSC homing and recruitment to the ischemic myocardium, and discuss potential influences of low engraftment rates of systemically administered MSCs to the infracted heart tissue on the effects of MSC-based therapies on myocardial infarction.

  17. Cardiac αVβ3 integrin expression following acute myocardial infarction in humans.

    PubMed

    Jenkins, William S A; Vesey, Alex T; Stirrat, Colin; Connell, Martin; Lucatelli, Christophe; Neale, Anoushka; Moles, Catriona; Vickers, Anna; Fletcher, Alison; Pawade, Tania; Wilson, Ian; Rudd, James H F; van Beek, Edwin J R; Mirsadraee, Saeed; Dweck, Marc R; Newby, David E

    2017-04-01

    Maladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The αvβ3 integrin receptor is a key mediator and determinant of cardiac repair. We aimed to establish whether αvβ3 integrin expression determines myocardial recovery following MI. (18)F-Fluciclatide (a novel αvβ3-selective radiotracer) positron emission tomography (PET) and CT imaging and gadolinium-enhanced MRI (CMR) were performed in 21 patients 2 weeks after ST-segment elevation MI (anterior, n=16; lateral, n=4; inferior, n=1). CMR was repeated 9 months after MI. 7 stable patients with chronic total occlusion (CTO) of a major coronary vessel and nine healthy volunteers underwent a single PET/CT and CMR. (18)F-Fluciclatide uptake was increased at sites of acute infarction compared with remote myocardium (tissue-to-background ratio (TBRmean) 1.34±0.22 vs 0.85±0.17; p<0.001) and myocardium of healthy volunteers (TBRmean 1.34±0.22 vs 0.70±0.03; p<0.001). There was no (18)F-fluciclatide uptake at sites of established prior infarction in patients with CTO, with activity similar to the myocardium of healthy volunteers (TBRmean 0.71±0.06 vs 0.70±0.03, p=0.83). (18)F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index≥1 vs 0; TBRmean 0.93±0.31 vs 0.80±0.26 respectively, p<0.001) and subendocardial infarction. Importantly, although there was no correlation with infarct size (r=0.03, p=0.90) or inflammation (C reactive protein, r=-0.20, p=0.38), (18)F-fluciclatide uptake was increased in segments displaying functional recovery (TBRmean 0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery. (18)F-Fluciclatide uptake is increased at sites of recent MI acting as a biomarker of cardiac repair and predicting regions of recovery. NCT01813045; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

  18. Cardiac αVβ3 integrin expression following acute myocardial infarction in humans

    PubMed Central

    Jenkins, William S A; Stirrat, Colin; Connell, Martin; Lucatelli, Christophe; Neale, Anoushka; Moles, Catriona; Vickers, Anna; Fletcher, Alison; Pawade, Tania; Wilson, Ian; van Beek, Edwin J R; Mirsadraee, Saeed; Dweck, Marc R; Newby, David E

    2017-01-01

    Objective Maladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The αvβ3 integrin receptor is a key mediator and determinant of cardiac repair. We aimed to establish whether αvβ3 integrin expression determines myocardial recovery following MI. Methods 18F-Fluciclatide (a novel αvβ3-selective radiotracer) positron emission tomography (PET) and CT imaging and gadolinium-enhanced MRI (CMR) were performed in 21 patients 2 weeks after ST-segment elevation MI (anterior, n=16; lateral, n=4; inferior, n=1). CMR was repeated 9 months after MI. 7 stable patients with chronic total occlusion (CTO) of a major coronary vessel and nine healthy volunteers underwent a single PET/CT and CMR. Results 18F-Fluciclatide uptake was increased at sites of acute infarction compared with remote myocardium (tissue-to-background ratio (TBRmean) 1.34±0.22 vs 0.85±0.17; p<0.001) and myocardium of healthy volunteers (TBRmean 1.34±0.22 vs 0.70±0.03; p<0.001). There was no 18F-fluciclatide uptake at sites of established prior infarction in patients with CTO, with activity similar to the myocardium of healthy volunteers (TBRmean 0.71±0.06 vs 0.70±0.03, p=0.83). 18F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index≥1 vs 0; TBRmean 0.93±0.31 vs 0.80±0.26 respectively, p<0.001) and subendocardial infarction. Importantly, although there was no correlation with infarct size (r=0.03, p=0.90) or inflammation (C reactive protein, r=−0.20, p=0.38), 18F-fluciclatide uptake was increased in segments displaying functional recovery (TBRmean 0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery. Conclusion 18F-Fluciclatide uptake is increased at sites of recent MI acting as a biomarker of cardiac repair and predicting regions of recovery. Trial registration number NCT01813045; Post-results. PMID:27927700

  19. Guidelines to reducing delays in administration of thrombolytic therapy in acute myocardial infarction.

    PubMed

    Williams, W L

    1998-05-01

    The thrombotic coronary accident that triggers a myocardial infarction initiates a 'wavefront' of ischaemic cell death that can be aborted by timely restoration of blood flow. Myocardium destined for necrosis can be salvaged by quick lysis of the culprit clot to restore perfusion, reduce infarct size and save lives. While a number of useful thrombolytic regimens have been investigated, the greatest barrier to optimising efficacy is reducing the delay between the onset of symptoms and administration of thrombolytic therapy. Clinical experience has confirmed laboratory evidence that prompt restoration of coronary blood flow can salvage more than 50% of ischaemic myocardium if achieved within 2 hours. However, after 6 hours of sustained ischaemia, the opportunity to achieve meaningful salvage is largely lost. Analysis of pooled data estimates that for each hour of delay 1.6 fewer lives are saved per 1000 patients treated. Other investigators have estimated 60 to 80 lives saved per 1000 patients treated within 1 hour of symptom onset. More realistically, the time from symptom onset to treatment averages 2.5 to 5 hours in various studies. Reluctance to seek medical help results in a delay of more than 4 hours in at least 40% of patients. There may be some benefits of late, time-independent reperfusion from 12 to 24 hours after symptoms. Some hibernating myocardium may be salvaged resulting in less adverse late ventricular remodelling, reduced infarction expansion and improved electrical stability. Barriers to timely thrombolytic treatment may be classified as presentation delay or treatment delay. Strategies to optimise timely treatment have included pre-hospital administration of thrombolytics. This achieves greatest benefit when used in a more rural setting where transportation times tend to be longer. In this setting, as much as 140 minutes has been shaved off the symptom-to-needle time with a 50% reduction in 3-month mortality sustained as a 30% reduction in 5-year

  20. Imaging necrotic myocardium: Detection with 99mTc-pyrophosphate and radiolabeled antimyosin

    SciTech Connect

    Khaw, B.A.; Haber, E. )

    1989-08-01

    The major value of hot-spot imaging of the myocardium is its ability to define areas of necrosis rather than areas of diminished blood flow or cellular function. Applications of hot-spot imaging include the diagnosis and quantitation of myocardial infarction, myocarditis, and cardiac transplant rejection. The two agents in clinical use, 99mTc-Pyrophosphate and radiolabeled antimyosin, are discussed. 52 references.

  1. Electrocardiographic infarct size assessment after thrombolysis: insights from the Acute Myocardial Infarction STudy ADenosine (AMISTAD) trial.

    PubMed

    Barbagelata, Alejandro; Di Carli, Marcelo F; Califf, Robert M; Garg, Jyotsna; Birnbaum, Yochai; Grinfeld, Liliana; Gibbons, Raymond J; Granger, Christopher B; Goodman, Shaun G; Wagner, Galen S; Mahaffey, Kenneth W

    2005-10-01

    Noninvasive methods are needed to evaluate reperfusion success in patients with acute myocardial infarction (MI). The AMISTAD trial was analyzed to compare MI size and myocardial salvage determined by electrocardiogram (ECG) with technetium Tc 99m sestamibi single-photon emission computerized tomography (SPECT) imaging. Of 236 patients enrolled in AMISTAD, 166 (70 %) with no ECG confounding factors and no prior MI were included in this analysis. Of these, group 1 (126 patients, 53%) had final infarct size (FIS) available by both ECG and SPECT. Group 2 (56 patients, 24%) had myocardium at risk, FIS, and salvage index (SI) assessed by both SPECT and ECG techniques. Aldrich/Clemmensen scores for myocardium at risk and the Selvester QRS score for final MI size were used. Salvage index was calculated as follows: SI = (myocardium at risk-FIS)/(myocardium at risk). In group 1, FIS was 15% (6, 24) as measured by ECG and 11% (2, 27) as measured by SPECT. In the adenosine group, FIS was 12% (6, 21) and 11% (2, 22). In the placebo group, FIS was 16.5% (7.5, 24) and 11.5% (3.0, 38.5) by ECG and SPECT, respectively. The overall correlation between SPECT and ECG for FIS was 0.58 (P = .0001): 0.60 in the placebo group (P = .0001) and 0.54 (P = .0001) in the adenosine group. In group 2, myocardium at risk was 23% (17, 30) and 26% (10, 50) with ECG and SPECT, respectively (P = .0066). Final infarct size was 17% (6, 21) and 12% (1, 24) (P < .0001). The SI was 29% (-7, 57) and 46% (15, 79) with ECG and SPECT, respectively (P = .0510). The ECG measurement of infarct size has a moderate relationship with SPECT infarct size measurements in the population with available assessments. This ECG algorithm must further be validated on clinical outcomes.

  2. Cardiac telocytes were decreased during myocardial infarction and their therapeutic effects for ischaemic heart in rat

    PubMed Central

    Zhao, Baoyin; Chen, Shang; Liu, Juanjuan; Yuan, Ziqiang; Qi, Xufeng; Qin, Junwen; Zheng, Xin; Shen, Xiaotao; Yu, Yanhong; Qnin, Thomas J; Chan, John Yeuk-Hon; Cai, Dongqing

    2013-01-01

    Recently, cardiac telocytes were found in the myocardium. However, the functional role of cardiac telocytes and possible changes in the cardiac telocyte population during myocardial infarction in the myocardium are not known. In this study, the role of the recently identified cardiac telocytes in myocardial infarction (MI) was investigated. Cardiac telocytes were distributed longitudinally and within the cross network of the myocardium, which was impaired during MI. Cardiac telocytes in the infarction zone were undetectable from approximately 4 days to 4 weeks after an experimental coronary occlusion was used to induce MI. Although cardiac telocytes in the non-ischaemic area of the ischaemic heart experienced cell death, the cell density increased approximately 2 weeks after experimental coronary occlusion. The cell density was then maintained at a level similar to that observed 1–4 days after left anterior descending coronary artery (LAD)-ligation, but was still lower than normal after 2 weeks. We also found that simultaneous transplantation of cardiac telocytes in the infarcted and border zones of the heart decreased the infarction size and improved myocardial function. These data indicate that cardiac telocytes, their secreted factors and microvesicles, and the microenvironment may be structurally and functionally important for maintenance of the physiological integrity of the myocardium. Rebuilding the cardiac telocyte network in the infarcted zone following MI may be beneficial for functional regeneration of the infarcted myocardium. PMID:23205601

  3. Postmortem detection of inapparent myocardial infarction

    PubMed Central

    McVie, J. G.

    1970-01-01

    Two methods of detecting early inapparent myocardial infarcts have been studied and their value in diagnostic practice compared. The better method proved to be the determination of the potassium to sodium ratio (ionic ratio) which falls in infarcted tissue within minutes of the onset of anoxia. The second method was nitro blue tetrazolium staining of gross sections of myocardium which revealed any infarct older than three and a half hours. As staining is dependent upon enzyme activity, the latter method is disturbed by autolysis. It was shown, on the other hand, that the ionic ratio (K+/Na+) was not affected by autolysis and was therefore well suited to forensic practice. Sixteen non-infarcted control hearts, plus the nine from cases of sudden death due to causes other than myocardial infarction, all yielded high ionic ratios (K+/Na+), average 1·4, and stained normally with tetrazolium (the normal controls). Positive control was provided by 20 histologically proven infarcts of which the ionic ratios (K+/Na+) were all low (average 0·7). Histochemical staining with tetrazolium delineated infarcted areas in each case. In a series of 29 sudden deaths, a cause of death other than myocardial infarction was found at necropsy in nine, mentioned above as normal controls. The remaining 20 hearts were not infarcted histologically, but were shown to be infarcted by examination of the ionic ratios (K+/Na+). These ratios were low (average 0·8) including three borderline ratios. Confirmatory evidence of infarction included nitro blue tetrazolium staining which revealed infarcts in 10 of the 20 cases, and clinical and necropsy observations. The ionic ratio (K+/Na+) decreases as the age of the infarct increases for at least 24 hours. Thereafter as healing proceeds, the ratio gradually reverts to normal. Thus, previous infarction and replacement fibrosis do not significantly alter the ionic ratio (K+/Na+). Nor is it changed by left ventricular hypertrophy, the presence of

  4. Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction

    SciTech Connect

    Dae, M.W.; Herre, J.M.; O'Connell, J.W.; Botvinick, E.H.; Newman, D.; Munoz, L. )

    1991-05-01

    To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using I-123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findings in biopsy specimens. Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent. These findings suggest that (1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and (2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium.

  5. Multiscale Characterization of Impact of Infarct Size on Myocardial Remodeling in an Ovine Infarct Model.

    PubMed

    Zhang, Pei; Li, Tielou; Griffith, Bartley P; Wu, Zhongjun J

    2015-01-01

    The surviving myocardium initially compensates the loss of injured myocardium after myocardial infarction (MI) and gradually becomes progressively dysfunctional. There have been limited studies on the effect of infarct size on temporal and spatial alterations in the myocardium during progressive myocardial remodeling. MI with three infarct sizes, i.e. 15, 25 and 35% of the left ventricular (LV) wall, was created in an ovine infarction model. The progressive LV remodeling over a 12-week period was studied. Echocardiography, sonomicrometry, and histological and molecular analyses were carried out to evaluate cardiac function, regional tissue contractile function, structural remodeling and cardiomyocyte hypertrophy, and calcium handling proteins. Twelve weeks after MI, the 15, 25 and 35% MI groups had normalized LV end diastole volumes of 1.4 ± 0.2, 1.7 ± 0.3 and 2.0 ± 0.4 ml/kg, normalized end systole volumes of 1.0 ± 0.1, 1.0 ± 0.2 and 1.3 ± 0.3 ml/kg and LV ejection fractions of 43 ± 3, 42 ± 6 and 34 ± 4%, respectively. They all differed from the sham group (p < 0.05). All the three MI groups exhibited larger wall areal expansion (remodeling strain), larger cardiomyocyte size and altered expression of calcium handing proteins in the adjacent myocardium compared to the remote counterpart from the infarct. A significant correlation was found between cardiomyocyte size and remodeling strain in the adjacent zone. A comparative analysis among the three MI groups showed that a larger infarct size (35 vs. 15% MI) was associated with larger remodeling strain, more serious impairment in the cellular structure and composition, and regional contractile function at regional tissue level and LV function at organ level.

  6. Splenic infarction

    MedlinePlus

    Splenic infarction is the death of tissue (necrosis) in the spleen due to a blockage in blood flow. ... Common causes of splenic infarction include: Blood clots Blood diseases such as sickle cell anemia Infections such as endocarditis

  7. Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium.

    PubMed

    de Lorgeril, M; Rousseau, G; Basmadjian, A; St-Jean, G; Tran, D C; Latour, J G

    1990-01-01

    To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.

  8. 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% O2, 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

  9. [Climatologic parameters and myocardial infarction].

    PubMed

    Larcan, A; Gilgenkrantz, J M; Stoltz, J F; Lambert, H; Laprevote-Heully, M C; Evrard, D; Kempf, J B; Lambert, J

    1983-01-01

    535 patients admitted to hospital with myocardium infarct which was confirmed in a determined period and within a 80 kilometers radius from a city of the East of France were compared to the meteorological parameters of the day when the infarct occurred and of the day preceding its occurrence. On one hand, climatic parameters were selected: atmospheric pressure, temperature of the air under shelter, relative humidity, wind speed and wind direction, hydrometeors and electrometeors; on the other hand, parameters of solar and planetary activity: daily flare index, AA index, Ap index or daily planetary index, phases of the moon. The analytic study concerning all acute vascular accidents (infarcts and cerebral accidents all together) enabled to us to notice a higher frequency of vascular accidents in various meteorological circumstances: atmospheric pressure lower than 990 mb, temperature lower than 12 degrees, wind of sector North to South-South West, hoar-frost with fog, rain, snow, first quarter of the moon, daily flare index lower than 530, magnetic activity lower than 6. A factorial analysis of correspondence enabled to us to understand the problem better and to determine "an infarct area" in which main meteorological factors appeared: low or decreasing atmospheric pressure, relative or increasing humidity, clear or increasing solar activity, steady magnetic activity; other factors could play an apparently less important role: low temperature, snow, decrease of wind speed, full moon, wind of sector East to North-East, South-South West. Consequently it appeared in that study that the occurrence of myocardium infarct corresponded to a climatic tendency corresponding to cold, bad or deteriorating weather.

  10. Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused rat myocardium by long-circulating macromolecular and liposomal carriers

    PubMed Central

    Wang, LiNa; Yao, ChunXia; Wu, Fei; Lin, Xiao; Shen, Lan; Feng, Yi

    2015-01-01

    Drug delivery to ischemic myocardium is an enormous challenge. This work aimed to characterize cardiac delivery behaviors of mono-polyethylene glycosylated (PEGylated) conjugates and long-circulating liposomes (L-Lps) with Radix Ophiopogonis polysaccharide (ROP) as drug. The results showed that compared to native ROP, 32-, 52-, and 45-fold increases in blood half-life were achieved by 20-kDa PEG mono-modified ROP (P20k-R), 40-kDa PEG mono-modified ROP (P40k-R), and ROP-loaded L-Lp, respectively. With comparable blood pharmacokinetics, ROP-loaded L-Lp showed both significantly higher targeting efficacy and drug exposure in infarcted myocardium than P40k-R. With regard to P20k-R, both its targeting efficacy and its level in infarcted myocardium at 3 hours postdose were comparable to P40k-R, but its level in blood and myocardium reduced obviously faster. As a whole, the results indicate that both loading in L-Lps and mono-PEGylation are effective in targeting drug to ischemic myocardium, but the former appears to induce stronger effects. PMID:26425081

  11. Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused rat myocardium by long-circulating macromolecular and liposomal carriers.

    PubMed

    Wang, LiNa; Yao, ChunXia; Wu, Fei; Lin, Xiao; Shen, Lan; Feng, Yi

    2015-01-01

    Drug delivery to ischemic myocardium is an enormous challenge. This work aimed to characterize cardiac delivery behaviors of mono-polyethylene glycosylated (PEGylated) conjugates and long-circulating liposomes (L-Lps) with Radix Ophiopogonis polysaccharide (ROP) as drug. The results showed that compared to native ROP, 32-, 52-, and 45-fold increases in blood half-life were achieved by 20-kDa PEG mono-modified ROP (P(20k)-R), 40-kDa PEG mono-modified ROP (P(40k)-R), and ROP-loaded L-Lp, respectively. With comparable blood pharmacokinetics, ROP-loaded L-Lp showed both significantly higher targeting efficacy and drug exposure in infarcted myocardium than P(40k)-R. With regard to P(20k)-R, both its targeting efficacy and its level in infarcted myocardium at 3 hours postdose were comparable to P(40k)-R, but its level in blood and myocardium reduced obviously faster. As a whole, the results indicate that both loading in L-Lps and mono-PEGylation are effective in targeting drug to ischemic myocardium, but the former appears to induce stronger effects.

  12. Impaired oxidative phosphorylation in overtrained rat myocardium

    PubMed Central

    Kadaja, Lumme; Eimre, Margus; Paju, Kalju; Roosimaa, Mart; Põdramägi, Taavi; Kaasik, Priit; Pehme, Ando; Orlova, Ehte; Mudist, Margareeta; Peet, Nadezhda; Piirsoo, Andres; Seene, Teet; Gellerich, Frank N; Seppet, Enn K

    2010-01-01

    The present study was undertaken to characterize and review the changes in energy metabolism in rat myocardium in response to chronic exhaustive exercise. It was shown that a treadmill exercise program applied for six weeks led the rats into a state characterized by decreased performance, loss of body weight and enhanced muscle catabolism, indicating development of overtraining syndrome. Electron microscopy revealed disintegration of the cardiomyocyte structure, cellular swelling and appearance of peroxisomes. Respirometric assessment of mitochondria in saponin-permeabilized cells in situ revealed a decreased rate of oxidative phosphorylation (OXPHOS) due to diminished control over it by ADP and impaired functional coupling of adenylate kinase to OXPHOS. In parallel, reduced tissue content of cytochrome c was observed, which could limit the maximal rate of OXPHOS. The results are discussed with respect to relationships between the volume of work and corresponding energy metabolism. It is concluded that overtraining syndrome is not restricted to skeletal muscle but can affect cardiac muscle as well. PMID:21264069

  13. Shensong Yangxin (SSYX) ameliorates disordered excitation transmission by suppressing cardiac collagen hyperplasia in rabbits with chronic myocardial infarction.

    PubMed

    Dang, Song; Huang, Cong-Xin; Wang, Xi; Wang, Xin; Hu, Juan; Huang, He

    2016-04-01

    The traditional Chinese medicine Shensong Yangxin (SSYX) can improve the clinical symptoms of arrhythmia in an integrated manner. This study aimed to investigate the electrophysiological effect of SSYX on the hearts of myocardial-infarcted rabbits and further explore the mechanism by which SSYX alleviates myocardial fibrosis. Myocardial infarction (MI) was established in rabbits by ligation of the left circumflex coronary. The rabbits were treated with SSYX (0.5 g/kg/d) or saline for 8 weeks by oral administration. Microelectrode array (MEA) technology was used in vivo for extracellular electrophysiological recordings of the infarct border zone. Masson's trichrome staining was used to observe myocardial fibrosis. Western blotting was performed to evaluate the protein expression levels of collagen I (COL I) and collagen III (COL III). Quantitative real-time polymerase chain reaction (real-time PCR) was performed to evaluate the TGF-β1 and MMP-2 mRNA expression levels. The results showed that the total activation time (TAT) and the dispersion of TAT were significantly increased and the excitation propagation markedly disordered after MI. SSYX could significantly decrease TAT and the dispersion of TAT, and significantly ameliorate the chaotic spread pattern of excitation. Furthermore, SSYX treatment could significantly decrease COL I and COL III protein levels and down-regulate TGF-β1 and MMP-2 mRNA expression levels in MI rabbits. It was concluded that SSYX may ameliorate cardiac electrophysiological abnormalities in infarcted hearts by decreasing the protein levels of COL I and COL III, down-regulating the mRNA expression levels of TGF-β1 and MMP2, and thereby reducing adverse cardiac remodeling.

  14. [Physiopathology of left ventricular remodeling after myocardial infarction].

    PubMed

    Bassand, J P; Anguenot, T

    1991-12-01

    The geometry of both the infarcted and non-infarcted zone of the left ventricle changes after myocardial infarction. Two mechanisms are involved: expansion of the infarcted zone and secondary dilatation of the non-infarcted zone. The necrosed area undergoes an inflammatory reaction followed by fibrosis which end up as a sca within a period of a few days to a few weeks. During this period if fibrous scarring the infarcted, thinned myocardium undergoes progressive expansion which starts in the first hours of the myocardial infarction. The loss of left ventricular systolic function related to the infarct and volumic overload created by expansion of the infarct influence the secondary development of dilatation of the non-infarcted zones. This dilatation results in restoration of left ventricular stroke volume but at the price of increased wall stress, which itself induces compensatory wall hypertrophy. These phenomena are more pronounced when the initial infarction is extensive and if they are sustained, they result in definitive myocardial failure. Several factors influence remodeling: the size of the infarct, arterial patency, wall stress and the quality of the scarring process itself. Therapeutic interventions of each of these factors can influence the remodeling. Limitation of infarct size by thrombolytic therapy, arterial revascularisation, even when performed late, seem capable of limiting expansion of the necrosed zone. Pharmacodynamic intervention of left ventricular afterload also affects ventricular remodeling. Nitrate derivatives, vasodilator therapy in general and converting enzyme inhibitors have been shown to be effective.

  15. Biokinetics of radiolabeled Iodophenylpentadecanoic acid (I-123-IPPA) and thallium-201 in a rabbit model of chronic myocardial infarction measured using a series of thermoluminescent dosimeters

    NASA Astrophysics Data System (ADS)

    Medich, David Christopher

    1997-09-01

    The biokinetics of Iodophenylpentadecanoic acid (123I-IPPA) during a chronic period of myocardial infarction were determined and compared to 201Tl. IPPA was assessed as a perfusion and metabolic tracer in the scintigraphic diagnosis of coronary artery disease. The myocardial clearance kinetics were measured by placing a series of thermoluminescent dosimeters (TLDs) on normal and infarcted tissue to measure the local myocardial activity content over time. The arterial blood pool activity was fit to a bi-exponential function for 201Tl and a tri-exponential function for 123I-IPPA to estimate the left ventricle contribution to TLD response. At equilibrium, the blood pool contribution was estimated experimentally to be less than 5% of the total TLD response. The method was unable to resolve the initial uptake of the imaging agent due in part to the 2 minute TLD response integration time and in part to the 30 second lag time for the first TLD placement. A noticeable disparity was observed between the tracer concentrations of IPPA in normal and ischemic tissue of approximately 2:1. The fitting parameters (representing the biokinetic eigenvalue rate constants) were related to the fundamental rate constants of a recycling biokinetic model. The myocardial IPPA content within normal tissue was elevated after approximately 130 minutes post injection. This phenomenon was observed in all but one (950215) of the IPPA TLD kinetics curves.

  16. The therapeutic potential of hepatocyte growth factor for myocardial infarction and heart failure.

    PubMed

    Jin, Hongkui; Wyss, J Michael; Yang, Renhui; Schwall, Ralph

    2004-01-01

    Hepatocyte growth factor (HGF) is a cytokine whose multipotent actions are mediated by c-Met receptor. This review focuses on effects of HGF on myocardial infarction (MI) and heart failure. Circulating concentrations of HGF and myocardial concentrations of HGF and c-Met mRNA and protein are substantially increased following acute MI. HGF has been shown to be cardioprotective towards acute cardiac ischemia-reperfusion injury. Gene transfection of HGF into rat hearts attenuates acute ischemia injury. Administration of HGF protein reduces infarct size and increases cardiac performance in a rat model of acute ischemia/reperfusion. In contrast, acute blockade of endogenous HGF increases infarct size and mortality. These acute effects of HGF appear to be related to angiogenic and anti-apoptotic mechanisms. Recent studies demonstrate that post-MI treatment with HGF gene or protein attenuates chronic cardiac remodeling and dysfunction. In rats, HGF gene transfer following large MI results in preserved cardiac function and geometry in association with angiogenesis and reduced apoptosis, and treatment with recombinant HGF also significantly improves cardiac performance measured 8 weeks after MI. In mice, post-MI HGF gene therapy improves cardiac remodeling and dysfunction through hypertrophy of cardiomyocytes, infarct wall thickening, preservation of vessels, and antifibrosis. In addition, gene transfer of HGF improves cardiac remodeling, angiogenesis and regional myocardial function in the chronic ischemic myocardium of dogs. Together, these preclinical data highlight the significant acute and chronic cardioprotective effects of HGF following ischemic heart failure. Clinical trials are needed to investigate the therapeutic potential of HGF for postinfarction heart failure in humans.

  17. Detection and characterization of acute myocardial infarction in man with use of gated magnetic resonance.

    PubMed

    McNamara, M T; Higgins, C B; Schechtmann, N; Botvinick, E; Lipton, M J; Chatterjee, K; Amparo, E G

    1985-04-01

    To evaluate the capability of magnetic resonance imaging (MRI) in the detection and characterization of alterations in signal intensity and T2 relaxation time in acutely infarcted relative to normal myocardium 16 adult patients and normal volunteers were studied by electrocardiographically gated proton MRI. The seven volunteers were entirely asymptomatic and had no history of cardiovascular abnormality. The nine patients had each suffered an acute myocardial infarction within 5 to 12 days before the MRI studies. The diagnosis in each patient was confirmed by electrocardiographic (ECG) criteria and elevated levels of fractionated creatine kinase (CK) isoenzymes. Electrocardiographically gated MRI was performed with a superconducting system operating at 0.35 tesla. MRI demonstrated infarcted myocardium as a region of high signal intensity relative to that of adjacent normal myocardium; regions of high intensity corresponded anatomically to the site of infarction as defined by the ECG changes. The mean percent difference between normal and infarcted myocardium was substantially greater on 56 msec images (70.2 +/- 21.3%) compared with 28 msec images (27.1 +/- 13.6%). Region of interest analysis revealed that infarcted myocardium had a significantly (p less than .01) prolonged T2 relaxation time (mean T2 = 80.9 msec) relative to that in normal myocardium (mean T2 = 42.3 msec) and relative to the mean T2 of left ventricular myocardium in the volunteers (mean T2 = 42.4 msec). An additional finding for each patient with myocardial infarction was a high intraluminal flow signal on 56 msec images, but this was also observed in normal subjects and is therefore a nonspecific finding.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. [Ultrastructural changes in the undamaged areas of the myocardium in rats with ischaemic-metabolic cardiomyopathy (author's transl)].

    PubMed

    Zlatewa, M; Angelow, A

    1980-01-01

    The ultrastructural changes in the undamaged areas of the myocardium in rats with ischemic-metabolic cardiomyopathy induced by treatment with Na2HPO4, Sopolcort H, and adrenalin are studied. In the cardiac muscle cells that seem to be uninjured, by light-microscopic investigation considerable damages of the mitochondria, sarcoplasmatic reticulum, myofibrils and the intercalated discs are found. These damages show that the there are a heavy hypoxia and metabolic disturbances outside the infarcted zones. Probably, they have certain significance for the progression of the morbid process in the myocardium.

  19. Myocardial scar imaging by standard single-energy and dual-energy late enhancement CT: Comparison with pathology and electroanatomic map in an experimental chronic infarct porcine model.

    PubMed

    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

    Myocardial scar is a substrate for ventricular tachycardia and sudden cardiac death. Late enhancement 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). We aim to compare late enhancement CT using newer LE-DECT acquisition and single-energy LE-CT acquisitions with pathology and electroanatomic map (EAM) in an experimental chronic myocardial infarction (MI) porcine study. In 8 pigs with chronic myocardial infarction (59 ± 5 kg), we performed dual-source CT, EAM, and pathology. For CT imaging, we performed 3 acquisitions at 10 minutes after contrast administration: LE-CT 80 kV, LE-CT 100 kV, and LE-DECT with 2 postprocessing software settings. Of the sequences, LE-CT 100 kV provided the best contrast-to-noise ratio (all P ≤ .03) and correlation to pathology for scar (ρ = 0.88). LE-DECT overestimated scar (both P = .02), whereas LE-CT images did not (both P = .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). Standard single-energy LE-CT, particularly 100 kV, matched better to pathology and EAM than dual-energy LE-DECT for scar detection. Larger human trials as well as more technical studies that optimize varying different energies with newer hardware and software are warranted. Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  20. Cytokine mRNA expression in postischemic/reperfused myocardium.

    PubMed Central

    Herskowitz, A.; Choi, S.; Ansari, A. A.; Wesselingh, S.

    1995-01-01

    While the role of cytokines in mediating injury during hind limb skeletal muscle ischemia followed by reperfusion has recently been described, the role of cytokines in myocardial infarction and ischemia/reperfusion have remained relatively unexplored. We hypothesize that cytokines play an important role in the regulation of postischemic myocardial inflammation. This study reports the temporal sequence of proinflammatory cytokine gene expression in postischemic/reperfused myocardium and localizes interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)-protein by immunostaining. Rats were subjected to either permanent left anterior descending (LAD) occlusion or to 35 minutes of LAD occlusion followed by reperfusion and sacrificed up to 7 days later. Rat-specific oligonucleotide probes were used to semiquantitatively assess the relative expression of mRNA for TNF-alpha, IL-1 beta, IL-2, IL-6, interferon-gamma (IFN-gamma), and transforming growth factor-beta 1 (TGF-beta 1) utilizing the reverse transcriptase-polymerase chain reaction amplification technique. Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours. During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion. In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion. Immunostaining for IL-1 beta and TNF-alpha protein revealed two patterns of reactivity: 1) microvascular staining for both IL-1 beta and TNF-alpha protein only in postischemic reperfused myocardium in early post-reperfusion time points; and 2) staining of infiltrating macrophages in healing infarct zones which was most prominent at 7 days after permanent LAD occlusion

  1. [Stunned myocardium after acute ischemic stroke].

    PubMed

    Varela, Daniel; Díaz, Fernanda; Hlavnicka, Alejandro; Wainsztein, Néstor; Leiguarda, Ramón

    2006-01-01

    The so-called stunned myocardium, defined as transitory myocardial contractile dysfunction, has been clearly demonstrated in diverse clinical situations. However, stunned myocardium related to ischemic stroke has been poorly identified. We describe two patients with diagnosis of acute ischemic stroke who developed eletrocardiographic changes, cardiac enzyme increasing levels and myocardial dysfunction secondary to abnormal cardiac wall motion. At the same time the patients developed acute lung injury with rapid resolution, perhaps as a consequence of neurocardiogenic components.

  2. Characterization of nontransmural myocardial infarction by positron-emission tomography

    SciTech Connect

    Geltman, E.M.; Biello, D.; Welch, M.J.; Ter-Pogossian, M.M.; Roberts, R.; Sobel, B.E.

    1982-04-01

    The present study was performed to determine whether positron emission tomography (PET) performed after i.v. 11C-palmitate permits detection and characterization of nontransmural myocardial infarction. PET was performed after the i.v. injection of 11C-palmitate in 10 normal subjects, 24 patients with initial nontransmural myocardial infarction (defined electrocardiographically), and 22 patients with transmural infarction. Depressed accumulation of 11C-palmitate was detected with sagittal, coronal and transverse reconstructions, and quantified based on 14 contiguous transaxial reconstructions. Defects with homogeneously intense depression of accumulation of tracer were detected in all 22 patients with transmural infarction (100%). Abnormalities of the distribution of 11C-palmitate in the myocardium were detected in 23 patients with nontransmural infarction (96%). Thallium scintigrams were abnormal in only 11 of 18 patients with nontransmural infarction (61%). Tomographically estimated infarct size was greater among patients with transmural infarction (50.4 +/- 7.8 PET-g-Eq/m2 (+/- SEM SEM)) compared with those with nontransmural infarction (19 +/- 4 PET-g-Eq, p less than 0.01). Residual accumulation of 11C-palmitate within regions of infarction was more intensely depressed among patients with transmural compared to nontransmural infarction (33 +/- 1 vs 39 +/- 1% maximal myocardial radioactivity, p less than 0.01). Thus, PET and metabolic imaging with 11C-palmitate is a sensitive means of detecting, quantifying and characterizing nontransmural and transmural myocardial infarction.

  3. The effect of ibuprofen on accumulation of /sup 111/In-labeled platelets and leukocytes in experimental myocardial infarction

    SciTech Connect

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schork, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-11-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 (/sup 111/In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occlusion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p . 0.005). Quantification of the platelet-associated /sup 111/In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes accumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction.

  4. The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction

    SciTech Connect

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schark, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-11-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 (/sup 111/In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occulsion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p=0.005). Quantification of the platelet-associated /sup 111/In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes acumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction.

  5. Modeling the dispersion in electromechanically coupled myocardium

    PubMed Central

    Eriksson, Thomas S. E.; Prassl, Anton J.; Plank, Gernot; Holzapfel, Gerhard A.

    2014-01-01

    SUMMARY We present an approach to model the dispersion of fiber and sheet orientations in the myocardium. By utilizing structure parameters, an existing orthotropic and invariant-based constitutive model developed to describe the passive behavior of the myocardium is augmented. Two dispersion parameters are fitted to experimentally observed angular dispersion data of the myocardial tissue. Computations are performed on a unit myocardium tissue cube and on a slice of the left ventricle indicating that the dispersion parameter has an effect on the myocardial deformation and stress development. The use of fiber dispersions relating to a pathological myocardium had a rather big effect. The final example represents an ellipsoidal model of the left ventricle indicating the influence of fiber and sheet dispersions upon contraction over a cardiac cycle. Although only a minor shift in the pressure–volume (PV) loops between the cases with no dispersions and with fiber and sheet dispersions for a healthy myocardium was observed, a remarkably different behavior is obtained with a fiber dispersion relating to a diseased myocardium. In future simulations, this dispersion model for myocardial tissue may advantageously be used together with models of, for example, growth and remodeling of various cardiac diseases. PMID:23868817

  6. Chronic Exposure to Low Doses of HgCl2 Avoids Calcium Handling Impairment in the Right Ventricle after Myocardial Infarction in Rats

    PubMed Central

    Faria, Thaís de Oliveira; Costa, Gustavo Pinto; Almenara, Camila Cruz Pereira; Angeli, Jhuli Keli; Vassallo, Dalton Valentim; Stefanon, Ivanita; Vassallo, Paula Frizera

    2014-01-01

    Right ventricle systolic dysfunction is a major risk factor for death and heart failure after myocardial infarction (MI). Heavy metal exposure has been associated with the development of several cardiovascular diseases, such as MI. The aim of this study was to investigate whether chronic exposure to low doses of mercury chloride (HgCl2) enhances the functional deterioration of right ventricle strips after MI. Male Wistar rats were divided into four groups: Control (vehicle); HgCl2 (exposure during 4 weeks- 1st dose 4.6 µg/kg, subsequent dose 0.07 µg/kg/day, i.m. to cover daily loss); MI surgery induced and HgCl2-MI groups. One week after MI, the morphological and hemodynamic measurements and isometric tension of right ventricle strips were investigated. The chronic HgCl2 exposure did not worsen the injury compared with MI alone in the morphological or hemodynamic parameters evaluated. At basal conditions, despite similar maximum isometric force at L-max, relaxation time was increased in the MI group but unaffected in the HgCl2-MI compared to the Control group. Impairment of the sarcoplasmic reticulum (SR) function and reduction in the sarcolemmal calcium influx were observed in MI group associated with SERCA2a reduction and increased PLB protein expression. Induction of MI in chronic HgCl2 exposed rats did not cause any alteration in the developed force at L-max, lusitropic function or −dF/dt except for a tendency of a reduction SR function. These findings could be partially explained by the normalization in the sarcolemmal calcium influx and the increase in NCX protein expression observed only in this group. These results suggest that chronic exposure to low doses of HgCl2 prevents the impaired SR function and the reduced sarcolemmal calcium influx observed in MI likely by acting on NCX, PLB and SERCA2a protein expression. PMID:24748367

  7. Myocardial infarct: depiction with contrast-enhanced MR imaging--comparison of gadopentetate and gadobenate.

    PubMed

    Schlosser, Thomas; Hunold, Peter; Herborn, Christoph U; Lehmkuhl, Heidrun; Lind, Alexander; Massing, Sandra; Barkhausen, Jörg

    2005-09-01

    Institutional review board approval and patient written informed consent were obtained. On two separate occasions, 24 hours apart, contrast-enhanced cardiac magnetic resonance (MR) imaging was performed prospectively at 1, 3, 5, 10, and 20 minutes after injection of gadopentetate dimeglumine and gadobenate dimeglumine in 15 patients (11 men, four women) with history of myocardial infarction. Both agents allowed detection of infarcted myocardium. T1 values at all times were significantly (P < .05) lower for gadobenate, compared with values for gadopentetate, in both infarcted and noninfarcted myocardium. At 1 minute after administration of both agents, T1 values in left ventricular cavity (LVC) were not different; at 3-20 minutes after injection, values were significantly (P < .05) lower for gadobenate. Differences between contrast-to-noise ratio (CNR) values of infarcted and noninfarcted myocardium were significantly higher on gadobenate-enhanced images (P < .05). CNR values between infarcted myocardium and LVC were significantly higher on gadopentetate-enhanced images (P < .05). Gadopentetate might permit better delineation of infarcts, especially subendocardial infarcts.

  8. Data mining framework for identification of myocardial infarction stages in ultrasound: A hybrid feature extraction paradigm (PART 2).

    PubMed

    Sudarshan, Vidya K; Acharya, U Rajendra; Ng, E Y K; Tan, Ru San; Chou, Siaw Meng; Ghista, Dhanjoo N

    2016-04-01

    Early expansion of infarcted zone after Acute Myocardial Infarction (AMI) has serious short and long-term consequences and contributes to increased mortality. Thus, identification of moderate and severe phases of AMI before leading to other catastrophic post-MI medical condition is most important for aggressive treatment and management. Advanced image processing techniques together with robust classifier using two-dimensional (2D) echocardiograms may aid for automated classification of the extent of infarcted myocardium. Therefore, this paper proposes novel algorithms namely Curvelet Transform (CT) and Local Configuration Pattern (LCP) for an automated detection of normal, moderately infarcted and severely infarcted myocardium using 2D echocardiograms. The methodology extracts the LCP features from CT coefficients of echocardiograms. The obtained features are subjected to Marginal Fisher Analysis (MFA) dimensionality reduction technique followed by fuzzy entropy based ranking method. Different classifiers are used to differentiate ranked features into three classes normal, moderate and severely infarcted based on the extent of damage to myocardium. The developed algorithm has achieved an accuracy of 98.99%, sensitivity of 98.48% and specificity of 100% for Support Vector Machine (SVM) classifier using only six features. Furthermore, we have developed an integrated index called Myocardial Infarction Risk Index (MIRI) to detect the normal, moderately and severely infarcted myocardium using a single number. The proposed system may aid the clinicians in faster identification and quantification of the extent of infarcted myocardium using 2D echocardiogram. This system may also aid in identifying the person at risk of developing heart failure based on the extent of infarcted myocardium.

  9. Efficacy of coronary angioplasty for the treatment of hibernating myocardium

    PubMed Central

    Fath-Ordoubadi, F; Beatt, K; Spyrou, N; Camici, P

    1999-01-01

    OBJECTIVES—To determine the efficacy of coronary angioplasty as the sole method of revascularisation in patients with coronary artery disease and chronically dysfunctional but viable myocardium (hibernating myocardium), and to assess the effect of restenosis on functional outcome.
DESIGN AND PATIENTS—24 consecutive patients with hibernating myocardium were studied. Positron emission tomography was used to assess myocardial viability, blood flow, and flow reserve. One patient refused angioplasty, one had bypass surgery, and one died while waiting for an elective procedure. The procedure failed in three patients. The remaining 18 patients had repeat echocardiography, 15 had repeat coronary angiography, and nine had repeat assessments of blood flow and flow reserve at mean (SD) 17 (2) weeks after angioplasty. In three patients restenosis was documented.
RESULTS—The wall motion score index in the revascularised territories improved from 1.71 (0.37) to 1.34 (0.47) (p = 0.008). Thirty of 51 dysfunctional segments improved in territories without restenosis compared with three of 14 in restenosed territories (p = 0.001). Hibernating and normal segments had comparable flows (0.82 (0.26) v 0.89 (0.24) ml/min/g; NS) while flow reserve was lower in hibernating segments (1.55 (0.68) v 2.07 (1.08); p = 0.03). In segments without restenosis flow reserve improved from 2.03 (1.25) to 2.33 (1.4) (p = 0.03). Sensitivity, specificity, and positive and negative predictive accuracy of the viability study were 97%, 77%, 82%, and 96%, respectively. After excluding patients with restenosis, specificity and positive predictive accuracy improved to 90% and 93%.
CONCLUSIONS—Angioplasty improves function in hibernating myocardium, and restenosis prevents recovery; hibernating myocardium is characterised by an impairment of flow reserve; restenosis affects the diagnostic accuracy of viability studies.


Keywords: coronary artery disease; percutaneous

  10. Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium. A computer modeling study.

    PubMed

    Lesh, M D; Pring, M; Spear, J F

    1989-11-01

    Although slow conduction is a requirement for the preparation of sustained reentry, it alone is not sufficient for the initiation of reentry. Additionally, unidirectional block and recovery of excitability distal to the site of block must occur. Thus, a comprehensive description of the electrophysiological determinants of reentry must explain both slow conduction and unidirectional block. Although there is a growing body of research exploring the influence of axial resistivity and anisotropy on slow conduction, somewhat less is known about the relation of axial resistivity to spatial dispersion of action potential duration, a condition favorable to the development of unidirectional block. We hypothesized that when cells are well coupled, local differences in intrinsic action potential duration are not evident and that, as axial resistivity increases, local variation in action potential duration becomes manifest. We tested this hypothesis in a numerical model of electrical propagation in a grid of resistively coupled ionic current sources simulating a sheet of ventricular myocardium. Spatial dispersion of intrinsic action potential duration was simulated by varying the magnitude of the fully activated slow inward conductance in Beeler-Reuter membrane ionic kinetics. By then altering coupling resistance, we showed that dispersion of manifest action potential duration is masked in the setting of normal low-resistance cellular coupling and unmasked by increased axial resistance. When nonuniform anisotropy was simulated, dramatic pacing-site-dependent changes in both the pattern of activation and dispersion of action potential duration were noted. These findings may be important in understanding the mechanism of reentrant tachycardia initiation in the border zone of chronic, healed myocardial infarctions where evidence suggests that abnormal cellular coupling is the predominant electrophysiological derangement. In this study, we have shown, using a detailed ionic

  11. Biodistribution, dosimetry, and clinical evaluation of technetium-99m ethyl cysteinate dimer in normal subjects and in patients with chronic cerebral infarction

    SciTech Connect

    Holman, B.L.; Hellman, R.S.; Goldsmith, S.J.; Mena, I.G.; Leveille, J.; Gherardi, P.G.; Moretti, J.L.; Bischof-Delaloye, A.; Hill, T.C.; Rigo, P.M.

    1989-06-01

    Technetium-99m ethyl cysteinate dimer (ECD) has high initial cerebral uptake with slow clearance in nonhuman primates suggesting ideal characteristics for single photon emission computer tomography (SPECT) imaging. We evaluated the biodistribution, dosimetry and scintigraphic pattern of (/sup 99m/Tc)ECD in normal subjects and the accuracy of SPECT imaging in patients with chronic cerebral infarction. Sixteen normal subjects were injected with approximately 10 mCi of (/sup 99m/Tc)ECD. Anterior and posterior single-pass whole-body images were obtained at multiple times after injection. Blood clearance of the radiotracer was rapid, falling to 10.0 +/- 6.6% and 4.9 +/- 1.1% of the injected dose at 2 and 60 min, respectively. Brain uptake was 6.4 +/- 2.1% of the injected dose 5 min after injection. The critical organ was the urinary bladder. Technetium-99m ECD SPECT was performed with a rotating gamma camera in ten of the 16 normal subjects and 34 patients with clinical and CT evidence of chronic stroke. Thirty-three of the thirty-four patients had focal (/sup 99m/Tc)ECD abnormalities on SPECT (97.1%) based on visual inspection of the SPECT images. In summary, we obtained high quality SPECT images as a result of the optimal physical and biologic characteristics of the tracer. Technetium-99m ECD SPECT shows promise for the evaluation of patients with stroke.

  12. 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

  13. Sinoatrial Node Reentry in a Canine Chronic Left Ventricular Infarct Model: The Role of Intranodal Fibrosis and Heterogeneity of Refractoriness

    PubMed Central

    Glukhov, Alexey V.; Hage, Lori T.; Hansen, Brian J.; Pedraza-Toscano, Adriana; Vargas-Pinto, Pedro; Hamlin, Robert L.; Weiss, Raul; Carnes, Cynthia A.; Billman, George E.; Fedorov, Vadim V.

    2014-01-01

    Background Reentrant arrhythmias involving the sinoatrial node (SAN), namely, SAN reentry, remain one of the most intriguing enigmas of cardiac electrophysiology. The goal of the present study was to elucidate the mechanism of SAN micro-reentry in canine hearts with post myocardial infarction (MI) structural remodeling. Methods and Results In vivo, Holter monitoring revealed ventricular arrhythmias and SAN dysfunctions in post left ventricular MI (6–15 wks) dogs (n=5) compared to control dogs (n=4). In vitro, high resolution near-infrared optical mapping of intramural SAN activation was performed in coronary perfused atrial preparations from MI (n=5) and controls (n=4). Both SAN macro- (slow-fast; 16–28 mm) and micro-reentries (1–3 mm) were observed in 60% of the MI preparations during moderate autonomic stimulation (acetylcholine (0.1 µM) or isoproterenol (0.01-0.1 µM)) after termination of atrial tachypacing (5–8 Hz), a finding not seen in controls. The autonomic stimulation induced heterogeneous changes in the SAN refractoriness; thus, competing atrial and/or SAN pacemaker waves could produce unidirectional blocks and initiate intranodal micro-reentries. The micro-reentry pivot waves were anchored to the longitudinal block region and produced both tachycardia and paradoxical bradycardia (due to exit block), despite an atrial ECG morphology identical to regular sinus rhythm. Intranodal longitudinal conduction blocks coincided with interstitial fibrosis strands that were exaggerated in the MI SAN pacemaker complex (fibrosis density 37±7% MI vs. 23±6% control, P<0.001). Conclusions Both tachy- and bradyarrhythmias can result from SAN micro-reentries. Post-infarction remodeling, including increased intranodal fibrosis and heterogeneity of refractoriness, provides substrates for SAN reentry. PMID:23960214

  14. Evaluation of the Effect of Concurrent Chronic Total Occlusion and Successful Staged Revascularization on Long-Term Mortality in Patients with ST-Elevation Myocardial Infarction

    PubMed Central

    Shi, Guoxiang; He, Pengcheng; Liu, Yuanhui; Lin, Yaowang; Yang, Xing; Chen, Jiyuan; Zhou, Yingling; Tan, Ning

    2014-01-01

    Aims. To investigate the impact of chronic total occlusion (CTO) in non-infarct-related artery (IRA) on the long-term prognosis and evaluate the clinical significance of staged revascularization in patients with ST-segment elevation myocardial infarction (STEMI). Methods. 1266 STEMI patients with primary percutaneous coronary intervention (PCI) were categorized as single-vessel disease (SVD), multivessel disease (MVD) without and with CTO. We study the clinical outcomes of patients after primary PCI in the following 3 years. Additionally, patients with CTO received staged revascularization, and major adverse cardiac events (MACE) during 3-year follow-up were recorded. Results. Presence of CTO was a predictor of both early mortality [hazard ratio (HR) 3.4, 95% confidence interval (CI) 2.4–4.5, P < 0.01] and late mortality (HR 1.9, 95% CI 1.4–3.6, P < 0.01), whereas MVD without CTO was only a predictor of early mortality (HR 1.7, 95% CI 1.3–2.3, P < 0.05). In CTO group, 100 patients had successful CTO recanalization, and 48 patients failed. During 3-year follow-up, patients with failed procedure had higher cardiac mortality (22.9% versus 9.0%, P = 0.020) and lower MACE-free survival (50.0% versus 72.0%, P = 0.009) compared to patients with successful procedure. Conclusion. The presence of CTO and not MVD alone is associated with long-term mortality. Successful revascularization of CTO in the non-IRA is associated with improved clinical outcomes in patients with STEMI undergoing primary PCI. PMID:24790581

  15. Impact of a chronic total occlusion in an infarct-related artery on the long-term outcome of ventricular tachycardia ablation.

    PubMed

    Di Marco, Andrea; Paglino, Gabriele; Oloriz, Teresa; Maccabelli, Giuseppe; Baratto, Francesca; Vergara, Pasquale; Bisceglia, Caterina; Anguera, Ignasi; Sala, Simone; Sora, Nicoleta; Dallaglio, Paolo; Marzi, Alessandra; Trevisi, Nicola; Mazzone, Patrizio; Della Bella, Paolo

    2015-05-01

    In patients with a prior myocardial infarction (MI), angiographic predictors of ventricular tachycardia (VT) recurrence after ablation are lacking. Recently, a proarrhythmic effect of a chronic total occlusion (CTO) in a coronary artery has been suggested. A total of 191 patients with prior MI were referred to our Hospital between 2010 and June 2013 for a first ablation of VT. Of these, 84 patients (44%) with stable coronary artery disease that underwent a coronary angiography during the index hospitalization were included in this study. A CTO in an infarct-related artery (IRA-CTO) was present in 47 patients (56%). Patients with and without IRA-CTO did not differ in terms of comorbidities, severity of heart failure, presentation of VT or acute outcome of ablation, that was completely successful in 93% of cases. At electroanatomic mapping, IRA-CTO was associated with greater scar and especially with greater area of border zone (34 cm(2) vs. 19 cm(2) , P = 0.001). Median follow-up was 19 months (IQR 18). At follow-up, patients with IRA-CTO had a significantly higher rate of VT recurrence (47% vs. 16%, P = 0.003). At multivariate analysis, IRA-CTO resulted to be an independent predictor of VT recurrence after ablation (HR 4.05, P = 0.004). IRA-CTO is an independent predictor of VT recurrence after ablation and identifies a subgroup of patients with high recurrence rate despite a successful procedure. IRA-CTO is associated with greater scars and border zone area; however, this association does not completely justify its proarrhythmic effect. © 2015 Wiley Periodicals, Inc.

  16. Chronic emotional stress exposure increases infarct size in rats: the role of oxidative and nitrosative damage in response to sympathetic hyperactivity.

    PubMed

    Mercanoglu, G; Safran, N; Uzun, H; Eroglu, L

    2008-12-01

    We investigated the level of sympathetic hyperactivity in response to stress exposure in an acute myocardial infarction (AMI) model and the contribution of oxidative and nitrosative damage to this phenomenon. Stress was induced by 20-day administration of different emotional stress factors: daylight/darkness exposure, overcrowding, isolation, new hierarchy, tilting the cage and restriction of water or food. AMI was induced surgically. Heart rate (HR) and heart rate variability (HRV) measurements were done before and after AMI. Oxidant parameters were measured in heart tissue and cortisol levels were measured in plasma specimens. Compared with the nonstressed group, stress-exposed rats showed sympathetic hyperactivity characterized by increased HR together with decreased HRV. In the stressed group serum corticosterone levels were high both before and after AMI. Mean infarct size in the stressed group was significantly larger (44.6+/-3.23% and 53.1+/-4.52%, respectively; P<0.05). Increased tissue malondialdehyde (MDA) levels (0.63+/-0.59 and 1.60+/-0.31 nmol/mg protein, respectively; P<0.05) and decreased superoxide dismutase (SOD) activity and glutathione (GSH) content were seen in stress-exposed rats. Likewise, heart peroxynitrite levels were also high in stress-exposed rats (141.8+/-18 nmol/g tissue vs. 164.2+/-21 nmol/g tissue). Chronic emotional stress is a deteriorating factor for the induction and prognosis of MI. Exaggerated sympathetic activity may be the major contributing factor. Oxidative and nitrosative damage in response to this sympathetic hyperactivity is the key mechanism.

  17. [The relationship between fragmented QRS complex and coronary collateral circulation in patients with chronic total occlusion lesion without prior myocardial infarction].

    PubMed

    Gu, X J; Shan, S J; Liu, Z Z; Jin, G Z; Hu, Z Y; Zhu, L L; Zhang, J

    2017-04-24

    Objective: To explore the relationship between fragmented QRS complex(fQRS) and coronary collateral circulation(CCC) in patients with chronic total occlusion(CTO)lesion without prior myocardial infarction. Methods: This retrospective study analyzed 238 consecutive patients with CTO lesion in one of the major coronary arteries from May 2014 to October 2015 in our department. Patients were divided into poor CCC group (grade 0 and 1, 58 cases) and good CCC group(grade 2 and 3, 180 cases) based on Rentrop's classification of CCC. The fQRS was defined as the presence of an additional R wave or notching of R or S wave or the presence of fragmentation in two contiguous electrocardiogram leads corresponding to a major coronary artery territory. Multivariate logistic regression was used to analyze the relationship between CCC and fQRS on electrocardiogram. Results: Compared with good CCC group, patients in poor CCC group had older age((65.2±8.9)years old vs. (60.3±10.1) years old, P=0.03), higher plasma glucose ((7.22±3.00) mmol/L vs.(6.31±1.83)mmol/L, P=0.04), and lower left ventricular ejection fraction ((45.2±11.4)% vs. (51.2±13.5)%, P=0.02). None of patients had Rentrop grade 0, the presence of fQRS on ECG in patients with Rentrop grade 1, grade 2, and grade 3 CCC was 69.0% (40/58), 48.6% (35/72) , and 19.4% (21/108), respectively (P<0.01). The presence of fQRS were higher in poor CCC group than in good CCC group (69.0%(40/58)vs. 31.1%(56/180), P<0.01), and number of leads with fQRS were higher in poor CCC group than in good CCC group (3(0, 4)vs.0(0, 3), P<0.01). Multivariate logistic regression analysis demonstrated that poor CCC growth in patients with CTO lesion without prior myocardial infarction was independently related to the presence of fQRS (OR=3.659, 95%CI 1.619-8.217, P<0.01). Conclusion: Poor CCC in patients with CTO lesion without prior myocardial infarction is independently related to the presence of fQRS on electrocardiogram.

  18. Quantifying the Release of Biomarkers of Myocardial Necrosis from Cardiac Myocytes and Intact Myocardium.

    PubMed

    Marjot, Jack; Kaier, Thomas E; Martin, Eva D; Reji, Shiney S; Copeland, O'Neal; Iqbal, Mohammed; Goodson, Bob; Hamren, Sarah; Harding, Sian E; Marber, Michael S

    2017-05-01

    Myocardial infarction is diagnosed when biomarkers of cardiac necrosis exceed the 99th centile, although guidelines advocate even lower concentrations for early rule-out. We examined how many myocytes and how much myocardium these concentrations represent. We also examined if dietary troponin can confound the rule-out algorithm. Individual rat cardiac myocytes, rat myocardium, ovine myocardium, or human myocardium were spiked into 400-μL aliquots of human serum. Blood was drawn from a volunteer after ingestion of ovine myocardium. High-sensitivity assays were used to measure cardiac troponin T (cTnT; Roche, Elecsys), cTnI (Abbott, Architect), and cardiac myosin-binding protein C (cMyC; EMD Millipore, Erenna(®)). The cMyC assay could only detect the human protein. For each rat cardiac myocyte added to 400 μL of human serum, cTnT and cTnI increased by 19.0 ng/L (95% CI, 16.8-21.2) and 18.9 ng/L (95% CI, 14.7-23.1), respectively. Under identical conditions cTnT, cTnI, and cMyC increased by 3.9 ng/L (95% CI, 3.6-4.3), 4.3 ng/L (95% CI, 3.8-4.7), and 41.0 ng/L (95% CI, 38.0-44.0) per μg of human myocardium. There was no detectable change in cTnI or cTnT concentration after ingestion of sufficient ovine myocardium to increase cTnT and cTnI to approximately 1 × 10(8) times their lower limits of quantification. Based on pragmatic assumptions regarding cTn and cMyC release efficiency, circulating species, and volume of distribution, 99th centile concentrations may be exceeded by necrosis of 40 mg of myocardium. This volume is much too small to detect by noninvasive imaging. © 2017 American Association for Clinical Chemistry.

  19. Reduced expression of CRHR2 and Sp-1 in myocardium of ovariectomized rats is improved by exercise training.

    PubMed

    Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Cong, Binhai; Lu, Jianqiang

    2015-01-01

    Exercise training has been looked on as a non-pharmacologic approach to treating ovariectomy (OVX)-induced dysfunctions. In this study, we investigated whether chronic exercise impacts on expression of urocortins (UCNs) and corticotropin-releasing hormone receptor type 2 (CRHR2) in myocardium of OVX rats. Bilateral OVX or sham-operation was performed under anesthesia. Both groups were then divided into two subgroups, with or without treadmill training for 8 weeks. It was found that OVX as well as exercise did not affect the mRNA levels of UCN, UCN2 and UCN3 in myocardium. OVX caused down-regulation of CRHR2 in myocardium. Exercise training reversed the OVX-induced reduction of CRHR2, but had no influence on CRHR2 level in sham rats. OVX resulted in a decrease in estrogen receptor α (ERα) expression in myocardium, which was restored by exercise. Moreover, exercise training also reversed OVX-induced down-regulation of specific protein-1 (Sp-1) expression in myocardium. CRHR2 expression level correlated with Sp-1 and ERα level in myocardium. These results indicate that exercise training can restore the CRHR2 level in myocardium of OVX rats, which is associated with ERα and Sp-1 expression.

  20. Risk stratification after acute myocardial infarction: which studies are best?

    PubMed

    Figueredo, V M

    1996-04-01

    The prognosis for a patient who has survived an acute myocardial infarction depends on three general prognostic factors: (1) residual left ventricular function, (2) remaining viable myocardium at risk (residual ischemia), and (3) presence of substrate for the development of malignant arrhythmias. Multiple clinical and historical factors predict the presence of one or more of these prognostic indicators. Electrocardiographic exercise treadmill testing needs to be done in all patients with uncomplicated infarctions. Guidelines of the American College of Cardiology/American Heart Association Task Force are recommended for risk stratification in most patients after acute myocardial infarction.

  1. Cardiomyocyte transplantation in a porcine myocardial infarction model.

    PubMed

    Watanabe, E; Smith, D M; Delcarpio, J B; Sun, J; Smart, F W; Van Meter, C H; Claycomb, W C

    1998-01-01

    Transplantation of cardiomyocytes into the heart is a potential treatment for replacing damaged cardiac muscle. To investigate the feasibility and efficiency of this technique, either a cardiac-derived cell line (HL-1 cells), or normal fetal or neonatal pig cardiomyocytes were grafted into a porcine model of myocardial infarction. The myocardial infarction was created by the placement of an embolization coil in the distal portion of the left anterior descending artery in Yorkshire pigs (n = 9). Four to 5 wk after creation of an infarct, the three preparations of cardiomyocytes were grafted, at 1 x 10(6) cells/20 microL into normal and into the middle of the infarcted myocardium. The hearts were harvested and processed for histologic examinations 4 to 5 wk after the cell grafts. Histologic evaluation of the graft sites demonstrated that HL-1 cells and fetal pig cardiomyocytes formed stable grafts within the normal myocardium without any detrimental effect including arrhythmia. In addition, a marked increase in angiogenesis was observed both within the grafts and adjacent host myocardium. Electron microscopy studies demonstrated that fetal pig cardiomyocytes and the host myocardial cells were coupled with adherens-type junctions and gap junctions. Histologic examination of graft sites from infarct tissue failed to show the presence of grafted HL-1 cells, fetal, or neonatal pig cardiomyocytes. Cardiomyocyte transplantation may provide the potential means for cell-mediated gene therapy for introduction of therapeutic molecules into the heart.

  2. Body mass index and myocardium at risk in patients with acute coronary syndrome.

    PubMed

    Arrebola-Moreno, A L; Marfil-Alvarez, R; Catena, A; García-Retamero, R; Arrebola, J P; Melgares-Moreno, R; Ramirez-Hernández, J A; Kaski, J C

    2014-04-01

    Whilst traditional studies have shown that obese individuals are at a higher risk of cardiovascular events compared to lean subjects, recent studies in patients with acute myocardial infarction (AMI) have suggested that obesity may exert protective effects (the "obesity paradox"). We sought to assess the relationship between body mass index (BMI) and the BARI score (BARIsc), a validated tool used to assess myocardium at risk, in patients with acute coronary syndrome. Participants were 116 consecutive patients (mean age, 60.6 years; 97 men) with AMI (68 ST elevated myocardial infarction, STEMI; 48 non-ST elevated myocardial infarction, NSTEMI). Demographics, BMI, risk factors, biochemistry data, left ventricular function, angiographic data and the BARIsc were assessed in every patient. Multiple linear regression analyses showed that BMI significantly correlated with BARIsc; β=.23, p<0.02. This was found only in the overweight/obese patients, β=.27, p<0.01, but not in patients with normal BMIs, β=0.08, p=0.71. An increased body weight is associated with an increased area of myocardium at risk in patients with ACS. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  3. Transmural versus nontransmural in situ electrical impedance spectrum for healthy, ischemic, and healed myocardium.

    PubMed

    Salazar, Yolocuauhtli; Bragos, Ramon; Casas, Oscar; Cinca, Juan; Rosell, Javier

    2004-08-01

    Electrical properties of myocardial tissue are anisotropic due to the complex structure of the myocardial fiber orientation and the distribution of gap junctions. For this reason, measured myocardial impedance may differ depending on the current distribution and direction with respect to myocardial fiber orientation and, consequently, according to the measurement method. The objective of this study is to compare the specific impedance spectra of the myocardium measured using two different methods. One method consisted of transmural measurements using an intracavitary catheter and the other method consisted of nontransmural measurements using a four-needle probe inserted into the epicardium. Using both methods, we provide the in situ specific impedance spectrum (magnitude and phase angle) of normal, ischemic, and infarcted pig myocardium tissue from 1 kHz to 1 MHz. Magnitude spectra showed no significant differences between the measurement techniques. However, the phase angle spectra showed significant differences for normal and ischemic tissues according to the measurement technique. The main difference is encountered after 60 min of acute ischeimia in the phase angle spectrum. Healed myocardial tissue showed a small and flat phase angle spectrum in both methods due tothe low content of cells in the transmural infarct scar. In conclusion, both transmural and nontransmural measurements of phase angle spectrum allow the differentiation among normal, ischemic, and infarcted tissue.

  4. Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction.

    PubMed

    Heidt, Timo; Courties, Gabriel; Dutta, Partha; Sager, Hendrik B; Sebas, Matt; Iwamoto, Yoshiko; Sun, Yuan; Da Silva, Nicolas; Panizzi, Peter; van der Laan, Anja M; van der Lahn, Anja M; Swirski, Filip K; Weissleder, Ralph; Nahrendorf, Matthias

    2014-07-07

    Macrophages populate the steady-state myocardium. Previously, all macrophages were thought to arise from monocytes; however, it emerged that, in several organs, tissue-resident macrophages may self-maintain through local proliferation. Our aim was to study the contribution of monocytes to cardiac-resident macrophages in steady state, after macrophage depletion in CD11b(DTR/+) mice and in myocardial infarction. Using in vivo fate mapping and flow cytometry, we estimated that during steady state the heart macrophage population turns over in ≈1 month. To explore the source of cardiac-resident macrophages, we joined the circulation of mice using parabiosis. After 6 weeks, we observed blood monocyte chimerism of 35.3±3.4%, whereas heart macrophages showed a much lower chimerism of 2.7±0.5% (P<0.01). Macrophages self-renewed locally through proliferation: 2.1±0.3% incorporated bromodeoxyuridine 2 hours after a single injection, and 13.7±1.4% heart macrophages stained positive for the cell cycle marker Ki-67. The cells likely participate in defense against infection, because we found them to ingest fluorescently labeled bacteria. In ischemic myocardium, we observed that tissue-resident macrophages died locally, whereas some also migrated to hematopoietic organs. If the steady state was perturbed by coronary ligation or diphtheria toxin-induced macrophage depletion in CD11b(DTR/+) mice, blood monocytes replenished heart macrophages. However, in the chronic phase after myocardial infarction, macrophages residing in the infarct were again independent from the blood monocyte pool, returning to the steady-state situation. In this study, we show differential contribution of monocytes to heart macrophages during steady state, after macrophage depletion or in the acute and chronic phase after myocardial infarction. We found that macrophages participate in the immunosurveillance of myocardial tissue. These data correspond with previous studies on tissue-resident macrophages

  5. Galectin-3 and post-myocardial infarction cardiac remodeling.

    PubMed

    Meijers, Wouter C; van der Velde, A Rogier; Pascual-Figal, Domingo A; de Boer, Rudolf A

    2015-09-15

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in order to preserve cardiac function. A hallmark herein is fibrosis formation, both in the early and late phase following acute myocardial infarction. Galectin-3, a β-galactoside-binding lectin, which is a shared factor in fibrosis formation in multiple organs, has an established role in cardiac fibrosis in the setting of pressure overload, neuro-endocrine activation and hypertension, but its role in post- myocardial infarction remodeling has received less attention. However, accumulative experimental studies have shown that myocardial galectin-3 expression is upregulated after myocardial infarction, both on mRNA and protein level. This already occurs shortly after myocardial infarction in the infarcted and border zone area, and also at a later stage in the spared myocardium, contributing to tissue repair and fibrosis. This is associated with typical aspects of fibrosis formation, such as apposition of matricellular proteins and increased factors of collagen turnover. Interestingly, myocardial fibrosis in experimental post-myocardial infarction cardiac remodeling could be attenuated by galectin-3 inhibition. In clinical studies, circulating galectin-3 levels have been shown to identify patients at risk for new-onset heart failure and atrial fibrillation. Circulating galectin-3 levels also predict progressive left ventricular dilatation after myocardial infarction. From literature we conclude that galectin-3 is an active player in cardiac remodeling after myocardial infarction. Future studies should focus on the dynamics of galectin-3 activation after myocardial infarction, and study the possibilities to target galectin-3.

  6. Benefits of Standardizing the Treatment of Arrhythmias in the Sheep (Ovis aries) Model of Chronic Heart Failure after Myocardial Infarction

    PubMed Central

    Dardenne, Adrienne; Fernandez, Carlos; Wagner, Alyssa; Milewski, Krzysztof; Ordanes, Diane R; Mount, Patricia A; Cheng, Yanping; Yi, Geng-Hua; Conditt, Gerard B; Tellez, Armando; Kaluza, Greg L; Granada, Juan F; Feeney, William P

    2013-01-01

    Large animal models of heart failure are essential in preclinical device testing. In sheep, catheter-based coil embolization of the left anterior descending and diagonal artery provides a minimally invasive and reproducible model of myocardial infarction (MI). Although widely used, this model has historically been plagued with a 30% mortality rate, both in the literature and in our own experience. Our study endeavored to decrease the mortality rate by targeting the most common cause of death, intractable arrhythmias, during creation of the ovine MI model. To this end, we evaluated 2 methods of managing perioperative antiarrhythmic therapy and cardiopulmonary resuscitation during model creation. The first group of sheep was managed at the discretion of the individual operator, whereas the second group was treated according to a standardized protocol that included mandatory pretreatment with amiodarone. Sheep experiencing life-threatening arrhythmias, most commonly ventricular fibrillation, were either resuscitated according to operator-driven instructions or the standardized protocol. By comparing these 2 treatment groups, we have shown that using a standardized protocol is advantageous in reducing mortality associated with the ovine MI model. Since implementing the standardized protocol, our laboratory has lowered the expected mortality rate to 10% during catheter-based induction of ovine MI and has greatly reduced the number of animals required for study needs. In addition, the standardized protocol has proven beneficial in training new staff members. By implementing this standardized method of model management, the outcomes of model creation have been optimized. PMID:23849412

  7. Regional sympathetic denervation after myocardial infarction: a follow-up study using [123I]MIBG.

    PubMed

    Podio, V; Spinnler, M T; Spandonari, T; Moretti, C; Castellano, G; Bessone, M; Brusca, A

    1995-12-01

    Previous studies in dogs have shown that experimental infarction produces myocardial sympathetic denervation not only in the infarcted area, but also in a region apical to the infarction. In these dogs MIBG myocardial scintigraphy detected denervation but returned to normal in a few months at which time reinnervation was shown to have occurred. Myocardial sympathetic denervation was studied with MIBG scintigraphy in ten patients after their first acute transmural myocardial infarction; scans were repeated at 4 months, one year and 30 months to follow the time course of possible reinnervation. Except during the first 48 hours following the infarction, no therapy except for antiaggregants was administered to the patients; during this follow-up period no cardiac events were seen. One week after infarction, comparison of MIBG images with perfusion scans revealed that the denervated area was larger than the infarcted area; no difference in MIBG uptake by the infarcted myocardium was found during the 30 months follow-up.

  8. Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challenges

    PubMed Central

    Saxena, Amit; Russo, Ilaria; Frangogiannis, Nikolaos G

    2015-01-01

    In the infarcted myocardium, necrotic cardiomyocytes release danger signals, activating an intense inflammatory response. Inflammatory pathways play a crucial role in regulation of a wide range of cellular processes involved in injury, repair and remodeling of the infarcted heart. Pro-inflammatory cytokines, such as tumor necrosis factor-a and interleukin (IL)-1, are markedly upregulated in the infarcted myocardium and promote adhesive interactions between endothelial cells and leukocytes, by stimulating chemokine and adhesion molecule expression. Distinct chemokine/chemokine receptor pairs are implicated in recruitment of various leukocyte subpopulations in the infarcted myocardium. Over the last 30 years, extensive experimental work has explored the role of inflammatory signals and the contributions of leukocyte subpopulations, in myocardial infarction. Robust evidence derived from experimental models of myocardial infarction has identified inflammatory targets that may attenuate cardiomyocyte injury, or protect from adverse remodeling. Unfortunately, attempts to translate the promising experimental findings to clinical therapy have failed. This review manuscript discusses the biology of the inflammatory response following myocardial infarction, attempts to identify the causes for the translational failures of the past, and proposes promising new therapeutic directions. Because of their potential involvement in injurious, reparative and regenerative responses, inflammatory cells may hold the key for design of new therapies in myocardial infarction. PMID:26241027

  9. 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

  10. Radioiodinated hypericin disulfonic acid sodium salts as a DNA-binding probe for early imaging of necrotic myocardium.

    PubMed

    Duan, Xinghua; Yin, Zhiqi; Jiang, Cuihua; Jin, Qiaomei; Zhang, Dongjian; Sun, Ziping; Ye, Wencai; Zhang, Jian

    2017-08-01

    Necrotic myocardium imaging can provide great indicators of salvaged myocardial areas for clinical guidances to patients with myocardial infarction (MI). One of the key challenges in necrotic myocardium imaging however, is lack of ideal necrotic imaging tracers for exactly and timely depicting the necrotic myocardium. (131)I-hypericin ((131)I-Hyp) is a promising tracer in exact necrotic myocardium delineation. However, it can't clearly image necrotic myocardium until 9h post injection (p.i.) for the high background signals in blood and lung due to the strong lipophilicity. Herein, an optimized (131)I-hypericin-2,5-disulfonic acid sodium salts ((131)I-Shyp) probe was synthesized for better pharmacokinetic and biodistribution properties to necrosis imaging. And the related mechanisms of necrotic avidity ability of (131)I-Hyp and (131)I-Shyp were also explored. In the results, (131)I-Shyp still showed selectively high accumulation in both necrotic cells and tissues. Biodistribution data revealed the decreased uptake of (131)I-Shyp in normal organs (lung, spleen and heart) and blood (as shown in pharmacokinetics studies). (131)I-Shyp presented quicker and clearer imaging for necrotic myocardium at 4h p.i. compared with (131)I-Hyp, suggesting that improved hydrophilicity of (131)I-Shyp may be conducive to its better pharmacokinetic and biodistribution properties to imaging. Additionally, DNA competitive binding assays and blocking experiments indicated that E-DNA is the possible target of Shyp and Hyp for their necrosis avidity. (131)I-Shyp may serve as a potential E-DNA targeted probe for necrotic myocardium imaging with molecular specificity for clinical use. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Exosomes and cardiac repair after myocardial infarction.

    PubMed

    Sahoo, Susmita; Losordo, Douglas W

    2014-01-17

    Myocardial infarction is a leading cause of death among all cardiovascular diseases. The analysis of molecular mechanisms by which the ischemic myocardium initiates repair and remodeling indicates that secreted soluble factors are key players in communication to local and distant tissues, such as bone marrow. Recently, actively secreted membrane vesicles, including exosomes, are being recognized as new candidates with important roles in intercellular and tissue-level communication. In this review, we critically examine the emerging role of exosomes in local and distant microcommunication mechanisms after myocardial infarction. A comprehensive understanding of the role of exosomes in cardiac repair after myocardial infarction could bridge a major gap in knowledge of the repair mechanism after myocardial injury.

  12. Collateral Circulation in Chronic Total Occlusions - an interventional perspective.

    PubMed

    Choo, Gim-Hooi

    2015-09-09

    Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

  13. Collateral Circulation in Chronic Total Occlusions - An Interventional Perspective

    PubMed Central

    Choo, Gim-Hooi

    2015-01-01

    Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

  14. Effect of chronic blockade of angiotensin II-receptor subtypes on aortic compliance in rats with myocardial infarction.

    PubMed

    Ceiler, D L; Nelissen-Vrancken, H J; De Mey, J G; Smits, J F

    1998-04-01

    This study was undertaken to investigate changes in aortic geometry and compliance after long-term blockade of angiotensin receptors type 1 (AT1) and AT2 receptors under basal conditions and after myocardial infarction (MI). Sham-operated (sham) or MI rats received either no treatment, AT1 antagonist GR138950C (GR; 2 mg/kg/day i.v.), or AT2 antagonist PD123319 (PD; 3 mg/kg/day s.c.). After 3 weeks, mean arterial blood pressure (MAP) was measured. Thoracic aorta diastolic diameter (D[dia]), compliance coefficient (CC), and distensibility coefficient (DC) were determined noninvasively in anesthetized rats by using ultrasound and wall tracking. After the rats were killed, histologic measurements were made on aortic cross sections. In sham rats, MAP was reduced by GR treatment (76 +/- 6 vs. 106 +/- 5 mm Hg), but not by PD. D(dia) was reduced in both GR-treated (1.74 +/- 0.08 vs. 2.09 +/- 0.05 mm) and PD-treated (1.83 +/- 0.05 vs. 2.09 +/- 0.05 mm) sham rats. CC and DC were not modified by either treatment. Although media cross-sectional area was not affected by either GR or PD treatment in sham rats, media thickness and media/lumen ratio were increased in both cases. Induction of MI had no effect on aortic structure, geometry, or mechanics; however, treatment with either GR or PD improved DC versus untreated MI rats. We conclude that AT1 and AT2 receptors are involved in angiotensin II-mediated effects on aortic geometry and mechanics under both basal conditions and after MI. Whereas blockade of AT1 receptors most likely influences vascular properties through a depressor mechanism, AT2 receptors induce pressure-independent remodeling.

  15. Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia.

    PubMed

    Bernaudin, Françoise; Verlhac, Suzanne; Arnaud, Cécile; Kamdem, Annie; Vasile, Manuela; Kasbi, Florence; Hau, Isabelle; Madhi, Fouad; Fourmaux, Christine; Biscardi, Sandra; Epaud, Ralph; Pondarré, Corinne

    2015-03-05

    Early transcranial Doppler (TCD) screening of the Créteil sickle cell anemia (SCA)-newborn cohort, and rapid initiation of transfusion programs, resulted in successful prevention of overt strokes, but a high cumulative risk of silent cerebral infarcts (SCI) remained, suggesting that TCD screening does not identify all patients with SCA at risk for SCI. We hypothesized that episodes of hypoperfusion/hypoxia, as observed during acute chest syndromes or acute anemic events (AAE), and extracranial internal carotid artery (eICA) stenoses, detectable via submandibular Doppler sonography and cervical magnetic resonance angiography (MRA), could also be risk factors for SCI. This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is a highly significant predictive risk factor for SCI (hazard ratio, 2.97; 95% CI, 1.43-6.17; P = .004). Furthermore, we show that AAE rate (odds ratio, 2.64 per unit increase; 95% CI, 1.09-6.38; P = .031) and isolated eICA stenosis (odds ratio, 3.19; 95% CI, 1.18-8.70; P = .023) are significant and independent risk factors for SCI.

  16. Differential regeneration of myocardial infarction depending on the progression of disease and the composition of biomimetic hydrogel.

    PubMed

    Yoon, So Jeong; Hong, Soyoung; Fang, Yong Hu; Song, Myeongjin; Son, Kuk Hui; Son, Ho Sung; Kim, Sook Kyoung; Sun, Kyung; Park, Yongdoo

    2014-10-01

    Hydrogel has been used for regenerating myocardial infraction (MI) as a delivery vehicle for cells and growth factors. This study showed that injectable hyaluronic acid (HA)-based hydrogels alone would effectively regenerate the damaged infarcted heart tissue. We found that there are two major factors of regeneration in MI. One is molecular weight of HA and another is the progression of MI; sub-acute and chronic. Rat MI model was prepared by ligating the left anterior descending coronary artery (LAD). Four weeks after injection of hydrogel, functional analysis of the heart and histological analysis was assessed. When different molecular weight HA-based hydrogels with 50 kDa, 130 kDa, and 170 kDa were applied to the infarcted area in the sub-acute model, 50 kDa HA-based hydrogel showed the most significant regeneration of myocardium as well as functional recovery among samples. For the disease progression, 50 kDa HA-based hydrogels were injected to sub-acute and chronic MI models. The regeneration activity was significantly decreased in the chronic models reflecting that injection timing of the therapeutic agents is also major determinants in the regeneration process. These results suggest that injection time and composition of hydrogel are two major points treating MI. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Resting thallium-201 myocardial perfusion patterns in patients with severe left ventricular dysfunction: differences between patients with primary cardiomyopathy, chronic coronary artery disease, or acute myocardial infarction

    SciTech Connect

    Iskandrian, A.S.; Hakki, A.H.; Kane, S.

    1986-04-01

    This study examined the value of resting thallium-201 imaging in differentiating patients with primary cardiomyopathy from those with ischemic cardiomyopathy. There were 15 patients with primary cardiomyopathy (group I); 20 with chronic CAD (group II); and 25 with acute Q wave myocardial infarction (group III). All patients had LVEF less than or equal to 35%. The thallium score was less than 50 (maximum 60) in one patient (7%) in group I, in 17 patients (85%) in group II, and in 25 patients (100%) in group III (p less than 0.0001, I vs II and III). The number of normal segments was 11.4 +/- 4.9 in group I, 6.9 +/- 2.9 in group II, and 7.0 +/- 2.2 in group III (p less than 0.0001, I vs II, III). Reversible defects were present in three patients in group II, three in group III, and none in group I. Abnormal right ventricular thallium uptake was observed in 27% of patients in group I, 25% in group II, and 40% in group III (p = NS). Abnormal lung thallium uptake was observed in 33% in group I, 20% in group II, and 20% in group III (p = NS). Thus, rest thallium imaging is useful in separating patients with primary cardiomyopathy from those with ischemic cardiomyopathy.

  18. Cardiac Function in a Long-Term Follow-Up Study of Moderate and Severe Porcine Model of Chronic Myocardial Infarction

    PubMed Central

    de Jong, Renate; van Hout, Gerardus P. J.; Houtgraaf, Jaco H.; Takashima, S.; Pasterkamp, Gerard; Hoefer, Imo; Duckers, Henricus J.

    2015-01-01

    Background. Novel therapies need to be evaluated in a relevant large animal model that mimics the clinical course and treatment in a reasonable time frame. To reliably assess therapeutic efficacy, knowledge regarding the translational model and the course of disease is needed. Methods. Landrace pigs were subjected to a transient occlusion of the proximal left circumflex artery (LCx) (n = 6) or mid-left anterior descending artery (LAD) (n = 6) for 150 min. Cardiac function was evaluated before by 2D echocardiography or 3D echocardiography and pressure-volume loop analysis. At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations. Results. Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group (−17.1 ± 1.6%, P = 0.009) compared to only a moderate reduction in the LCx group (−5.9 ± 1.5%, P = 0.02) and this effect remained unchanged during 12 weeks of follow-up. Conclusion. Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx. PMID:25802838

  19. Fluorescence spectroscopy to assess apoptosis in myocardium

    NASA Astrophysics Data System (ADS)

    Ranji, Mahsa; Matsubara, Muneaki; Grosso, Michael A.; Jaggard, Dwight L.; Chance, Britton; Gorman, Robert C.; Gorman, Joseph H., III

    2007-02-01

    Apoptosis induced mitochondrial destruction and dysfunction has been shown to play an important role in the pathogenesis of both acute cardiac ischemia-reperfusion injury and chronic myocardial infarction-induced ventricular remodeling. Unfortunately this understanding has not translated into effective therapeutic strategies for either condition-mostly due to an inability to assess mitochondrial dysfunction/apoptosis effectively in humans. All current measures of apoptosis are pseudo-quantitative and require invasive tissue biopsy. Our group has developed an optical, non-tissue destructive catheter based device that allows the quantitative regional assessment of this pathological process in vivo. This instrument has been designed to acquire fluorescence signals of intrinsic mitochondrial fluorophores, Nicotinamide Adenine Dinucleotide (NAD) and Flavoprotein (FP). The normalized ratio of these fluorophores (FP/FP+NADH) called the redox ratio, is an indicator of the in vivo mitochondrial dysfunction. 1-3 We have demonstrated in a rabbit reperfusion model of apoptotic myocyte injury that this redox ratio is drastically increased which is consistent with profound apoptosis-induced "unhinging" of the mitochondrial respiratory function.

  20. [Prognosis of the outcome of recurrent myocardial infarct].

    PubMed

    Ustinskova, N M; Syrkin, A L; Markova, A I; Zhuravel', A A

    1979-05-01

    The authors developed a method for prognosticating the outcome of recurrent myocardial infarction with the use of the Bayes formula. The diagnosis of recurrent myocardial infarction was made when necroses recurred in the myocardium during in-patient treatment for acute myocardial infarction. The prognosis was determined 72 hours after the recurrence of the necrosis. The prognostic signs characterized predominantly the degree of congestive circulatory failure and the frequency of disorders of cardiac rhythm in the acute period of myocardial infarction and recurrent myocardial infarction as well as in the interval betwen them (10 signs with informativeness of 0.117 to 0.05 were used.) The prognosis was erroneous in 8 of 70 patients who recovered from the disease and in 1 of 17 who died.

  1. Myocardium wall thickness transducer and measuring method

    NASA Technical Reports Server (NTRS)

    Feldstein, C.; Lewis, G. W.; Silver, R. H.; Culler, V. H. (Inventor)

    1976-01-01

    A miniature transducer for measuring changes of thickness of the myocardium is described. The device is easily implantable without traumatizing the subject, without affecting the normal muscle behavior, and is removable and implantable at a different muscle location. Operating features of the device are described.

  2. Neurogenic stunned myocardium in subarachnoid hemorrhage.

    PubMed

    Kerro, Ali; Woods, Timothy; Chang, Jason J

    2017-04-01

    "Stunned myocardium," characterized by reversible left ventricular dysfunction, was first described via animal models using transient coronary artery occlusion. However, this phenomenon has also been noted with neurologic pathologies and collectively been labeled "neurogenic stunned myocardium" (NSM). Neurogenic stunned myocardium resulting from subarachnoid hemorrhage (SAH) is a challenging pathology due to its diagnostic uncertainty. Traditional diagnostic criteria for NSM after SAH focus on electrocardiographic and echocardiographic abnormalities and troponemia. However, tremendous heterogeneity still exists. Traditional pathophysiological mechanisms for NSM encompassed hypothalamic and myocardial perivascular lesions. More recently, research on pathophysiology has centered on myocardial microvascular dysfunction and genetic polymorphisms. Catecholamine surging as a mechanism has also gained attention with particular focus placed on the role of adrenergic blockade in both the prehospital and acute settings. Management remains largely supportive with case reports acknowledging the utility of inotropes such as dobutamine and milrinone and intra-aortic balloon pump when NSM is accompanied by cardiogenic shock. Neurogenic stunned myocardium that follows SAH can result in many complications such as arrhythmias, pulmonary edema, and prolonged intubation, which can negatively impact long-term recovery from SAH and increase morbidity and mortality. This necessitates the need to accurately diagnose and treat NSM.

  3. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    PubMed Central

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  4. Role of Perfusion at Rest in the Diagnosis of Myocardial Infarction Using Vasodilator Stress Cardiovascular Magnetic Resonance.

    PubMed

    Patel, Mita B; Mor-Avi, Victor; Kawaji, Keigo; Nathan, Sandeep; Kramer, Christopher M; Lang, Roberto M; Patel, Amit R

    2016-04-01

    In clinical practice, perfusion at rest in vasodilator stress single-photon emission computed tomography is commonly used to confirm myocardial infarction (MI) and ischemia and to rule out artifacts. It is unclear whether perfusion at rest carries similar information in cardiovascular magnetic resonance (CMR). We sought to determine whether chronic MI is associated with abnormal perfusion at rest on CMR. We compared areas of infarct and remote myocardium in 31 patients who underwent vasodilator stress CMR (1.5 T), had MI confirmed by late gadolinium enhancement (LGE scar), and coronary angiography within 6 months. Stress perfusion imaging during gadolinium first pass was followed by reversal with aminophylline (75 to 125 mg), rest perfusion, and LGE imaging. Resting and peak-stress time-intensity curves were used to obtain maximal upslopes (normalized by blood pool upslopes), which were compared between infarcted and remote myocardial regions of interest. At rest, there was no significant difference between the slopes in the regions of interest supplied by arteries with and without stenosis >70% (0.31 ± 0.16 vs 0.26 ± 0.15 1/s), irrespective of LGE scar. However, at peak stress, we found significant differences (0.20 ± 0.11 vs 0.30 ± 0.22 1/s; p <0.05), reflecting the expected stress-induced ischemia. Similarly, at rest, there was no difference between infarcted and remote myocardium (0.27 ± 0.14 vs 0.30 ± 0.17 1/s), irrespective of stenosis, but significant differences were seen during stress (0.21 ± 0.16 vs 0.28 ± 0.18 1/s; p <0.001), reflecting inducible ischemia. In conclusion, abnormalities in myocardial perfusion at rest associated with chronic MI are not reliably detectable on CMR images. Accordingly, unlike single-photon emission computed tomography, normal CMR perfusion at rest should not be used to rule out chronic MI. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Epicardial, endocardial and transmural mapping in assessing electrophysiological effects of 14-C lidocaine and 14-C propafenone on activation times in experimental chronic myocardial infarction. Correlations with myocardial drugs concentrations.

    PubMed

    Naccarella, F F; Agarwal, J B; Weintraub, W S; Bracchetti, D; Helfant, R H

    1984-10-01

    The electrophysiological effects of lidocaine (L) and propafenone (P) in chronic myocardial infarction in relation to tissue drug concentrations (TDC) are unknown. Thus of 16 dogs with one week old myocardial infarction, 8 received propafenone 2 mg/kg and 8 lidocaine 5 mg/kg followed by 0.2 mg/kg/min of either drug for 60 min. Epicardial (EPI) mapping (greater than 30 points) was performed with a bipolar electrode. Endocardial (ENDO) and transmural (TRANS) mapping (greater than 20 points) were performed with 4 pairs of needle mounted bipolar electrodes. The % change in activation times (% delta AT) in EPI, ENDO and TRANS was evaluated in normal (N) and infarcted (I) zones at control and 60 min after drugs. Ventricular arrhythmias (VA) were studied with programmed extra stimulation. Results (P less than 0.01 to L, P less than 0.01 to N zone, # P less than 0.05 to ENDO): (Table: see text) At 60' ventricular tachycardia and ventricular fibrillation were both still inducible in 50% in the lidocaine group (37% in control), while only in 16% in the propafenone group (62% in control). Despite lower drug concentrations in the infarct, the effects on AT are comparable to normal zones for both drugs. In conclusion lidocaine reduces and propafenone increases AT, affecting in opposite directions the inducibility of reentrant ventricular arrhythmias.

  6. Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

    PubMed Central

    Galagudza, Michael; Korolev, Dmitry; Postnov, Viktor; Naumisheva, Elena; Grigorova, Yulia; Uskov, Ivan; Shlyakhto, Eugene

    2012-01-01

    Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery. PMID:22619519

  7. Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic myocardial infarction even when the absolute atrioventricular plane displacement is decreased.

    PubMed

    Asgeirsson, Daniel; Hedström, Erik; Jögi, Jonas; Pahlm, Ulrika; Steding-Ehrenborg, Katarina; Engblom, Henrik; Arheden, Håkan; Carlsson, Marcus

    2017-07-28

    The majority (60%) of left ventricular (LV) stroke volume (SV) is generated by longitudinal shortening causing apical atrioventricular plane displacement (AVPD) in systole. The remaining SV is caused by radial inward motion of the epicardium both in the septal and the lateral wall. We aimed to determine if these longitudinal, septal and lateral contributions to LVSV are changed in patients with chronic myocardial infarction (MI). Patients with a chronic (>3 months) ST-elevation MI in the left anterior descending (LAD, n = 20) or right coronary artery (RCA, n = 16) and healthy controls (n = 20) were examined with cardiovascular magnetic resonance (CMR). AVPD was quantified in long axis cine CMR images and LV volumes and dimensions in short axis cine images. AVPD was decreased both in patients with LAD-MI (11 ± 1 mm, p < 0.001) and RCA-MI (13 ± 1 mm, p < 0.05) compared to controls (15 ± 0 mm). However, the longitudinal contribution to SV was unchanged for both LAD-MI (58 ± 3%, p = 0.08) and RCA-MI (59 ± 3%, p = 0.09) compared to controls (64 ± 2%). The preserved longitudinal contribution despite decreased absolute AVPD was a results of increased epicardial dimensions (p < 0.01 for LAD-MI and p = 0.06 for RCA-MI). In LAD-MI the septal contribution to LVSV was decreased (5 ± 1%) compared to both controls (10 ± 1%, p < 0.01) and patients with RCA-MIs (10 ± 1%, p < 0.01). The lateral contribution was increased in LAD-MI patients (44 ± 3%) compared to both RCA-MI (35 ± 2%, p < 0.05) and controls (29 ± 2%, p < 0.001). Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic MI even when the absolute AVPD is decreased.

  8. Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III–V, and ESRD

    PubMed Central

    Saad, Marc; Karam, Boutros; Faddoul, Geovani; Douaihy, Youssef El; Yacoub, Harout; Baydoun, Hassan; Boumitri, Christine; Barakat, Iskandar; Saifan, Chadi; El-Charabaty, Elie; Sayegh, Suzanne El

    2016-01-01

    Patients with chronic kidney disease (CKD) are three times more likely to have myocardial infarction (MI) and suffer from increased morbidity and higher mortality. Traditional and unique risk factors are prevalent and constitute challenges for the standard of care. However, CKD patients have been largely excluded from clinical trials and little evidence is available to guide evidence-based treatment of coronary artery disease in patients with CKD. Our objective was to assess whether a difference exists in the management of MI (ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction) among patients with normal kidney function, CKD stage III–V, and end-stage renal disease (ESRD) patients. We conducted a retrospective cohort study on patients admitted to Staten Island University Hospital for the diagnosis of MI between January 2005 and December 2012. Patients were assigned to one of three groups according to their kidney function: Data collected on the medical management and the use of statins, platelet inhibitors, beta-blockers, and angiotensin converting enzyme inhibitors/angiotensin receptor blockers were compared among the three cohorts, as well as medical interventions including: catheterization and coronary artery bypass graft (CABG) when indicated. Chi-square test was used to compare the proportions between nominal variables. Binary logistic analysis was used in order to determine associations between treatment modalities and comorbidities, and to account for possible confounding factors. Three hundred and thirty-four patients (mean age 67.2±13.9 years) were included. In terms of management, medical treatment was not different among the three groups. However, cardiac catheterization was performed less in ESRD when compared with no CKD and CKD stage III–V (45.6% vs 74% and 93.9%) (P<0.001). CABG was performed in comparable proportions in the three groups and CABG was not associated with the degree of CKD (P=0.078) in

  9. Gene expression profiling of human hibernating myocardium: increased expression of B-type natriuretic peptide and proenkephalin in hypocontractile vs normally-contracting regions of the heart.

    PubMed

    Prasad, Sanjay K; Clerk, Angela; Cullingford, Timothy E; Chen, Alexander W Y; Kemp, Timothy J; Cannell, Timothy M; Cowie, Martin R; Petrou, Mario

    2008-12-01

    A greater understanding of the molecular basis of hibernating myocardium may assist in identifying those patients who would most benefit from revascularization. Paired heart biopsies were taken from hypocontractile and normally-contracting myocardium (identified by cardiovascular magnetic resonance) from 6 patients with chronic stable angina scheduled for bypass grafting. Gene expression profiles of hypocontractile and normally-contracting samples were compared using Affymetrix microarrays. The data for patients with confirmed hibernating myocardium were analysed separately and a different, though overlapping, set (up to 380) of genes was identified which may constitute a molecular fingerprint for hibernating myocardium. The expression of B-type natriuretic peptide (BNP) was increased in hypocontractile relative to normally-contracting myocardium. The expression of BNP correlated most closely with the expression of proenkephalin and follistatin 3, which may constitute additional heart failure markers. Our data illustrate differential gene expression in hypocontractile and/hibernating myocardium relative to normally-contracting myocardium within individual human hearts. Changes in expression of these genes, including increased relative expression of natriuretic and other factors, may constitute a molecular signature for hypocontractile and/or hibernating myocardium.

  10. Harm Avoidance and Cerebral Infarction

    PubMed Central

    Wilson, Robert S.; Boyle, Patricia A.; Levine, Steven R.; Yu, Lei; Hoganson, George M.; Buchman, Aron S.; Schneider, Julie A.; Bennett, David A.

    2014-01-01

    Objective Harm avoidance, a trait indicative of behavioral inhibition, is associated with disability and dementia in old age, but the basis of these associations is uncertain. We test the hypothesis that higher level of harm avoidance is associated with increased likelihood of cerebral infarction. Methods Older persons without dementia completed a standard measure of harm avoidance. During a mean of 3.5 years of follow-up, 257 (of 1,082) individuals died of whom 206 (80%) underwent brain autopsy. Number of chronic cerebral infarcts (microscopic plus gross; expressed as 0,1, or >1) was assessed on neuropathologic examination, completed in 192 individuals at the time of analyses. Results On postmortem examination, chronic cerebral infarcts were found in 89 (42 with 1, 47 with >1). Higher harm avoidance was associated with higher likelihood of infarcts (odds ratio = 1.083, 95% confidence interval 1.040–1.128). A moderately high level of the trait (score=17, 75th percentile) was associated with a 2.4-fold increase in the likelihood of infarction compared to a moderately low level of the trait (score = 6, 25th percentile). These associations persisted in models that controlled for other cardiovascular risk factors. Conclusion Higher level of the harm avoidance trait may be a risk factor for cerebral infarction. PMID:24364391

  11. [Myocardial infarction and acute coronary syndrome: definitions, classification, and diagnostic criteria].

    PubMed

    Zaĭrat'iants, O V; Mishnev, O D; Kakturskiĭ, L V

    2014-01-01

    The review gives the definitions and classification of and diagnostic criteria for myocardial infarction and acute coronary syndrome in accordance with the "The third universal definition of myocardial infarction" adopted in 2012 (Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, 2012). It also discusses the clinical and morphological comparisons of and the problems in the differential diagnosis of myocardial infarction as a nosological entity within coronary heart disease with other coronarogenic and non-coronarogenic necroses of the myocardium.

  12. Cardiac telocytes were decreased during myocardial infarction and their therapeutic effects for ischaemic heart in rat.

    PubMed

    Zhao, Baoyin; Chen, Shang; Liu, Juanjuan; Yuan, Ziqiang; Qi, Xufeng; Qin, Junwen; Zheng, Xin; Shen, Xiaotao; Yu, Yanhong; Qnin, Thomas J; Chan, John Yeuk-Hon; Cai, Dongqing

    2013-01-01

    Recently, cardiac telocytes were found in the myocardium. However, the functional role of cardiac telocytes and possible changes in the cardiac telocyte population during myocardial infarction in the myocardium are not known. In this study, the role of the recently identified cardiac telocytes in myocardial infarction (MI) was investigated. Cardiac telocytes were distributed longitudinally and within the cross network of the myocardium, which was impaired during MI. Cardiac telocytes in the infarction zone were undetectable from approximately 4 days to 4 weeks after an experimental coronary occlusion was used to induce MI. Although cardiac telocytes in the non-ischaemic area of the ischaemic heart experienced cell death, the cell density increased approximately 2 weeks after experimental coronary occlusion. The cell density was then maintained at a level similar to that observed 1-4 days after left anterior descending coronary artery (LAD)-ligation, but was still lower than normal after 2 weeks. We also found that simultaneous transplantation of cardiac telocytes in the infarcted and border zones of the heart decreased the infarction size and improved myocardial function. These data indicate that cardiac telocytes, their secreted factors and microvesicles, and the microenvironment may be structurally and functionally important for maintenance of the physiological integrity of the myocardium. Rebuilding the cardiac telocyte network in the infarcted zone following MI may be beneficial for functional regeneration of the infarcted myocardium. © 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  13. Unsupervised 4D myocardium segmentation with a Markov Random Field based deformable model.

    PubMed

    Cordero-Grande, L; Vegas-Sánchez-Ferrero, G; Casaseca-de-la-Higuera, P; San-Román-Calvar, J Alberto; Revilla-Orodea, Ana; Martín-Fernández, M; Alberola-López, C

    2011-06-01

    A stochastic deformable model is proposed for the segmentation of the myocardium in Magnetic Resonance Imaging. The segmentation is posed as a probabilistic optimization problem in which the optimal time-dependent surface is obtained for the myocardium of the heart in a discrete space of locations built upon simple geometric assumptions. For this purpose, first, the left ventricle is detected by a set of image analysis tools gathered from the literature. Then, the segmentation solution is obtained by the Maximization of the Posterior Marginals for the myocardium location in a Markov Random Field framework which optimally integrates temporal-spatial smoothness with intensity and gradient related features in an unsupervised way by the Maximum Likelihood estimation of the parameters of the field. This scheme provides a flexible and robust segmentation method which has been able to generate results comparable to manually segmented images for some derived cardiac function parameters in a set of 43 patients affected in different degrees by an Acute Myocardial Infarction. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Diabetes Mellitus-Induced Microvascular Destabilization in the Myocardium.

    PubMed

    Hinkel, Rabea; Howe, Andrea; Renner, Simone; Ng, Judy; Lee, Seungmin; Klett, Katharina; Kaczmarek, Veronika; Moretti, Alessandra; Laugwitz, Karl-Ludwig; Skroblin, Philipp; Mayr, Manuel; Milting, Hendrik; Dendorfer, Andreas; Reichart, Bruno; Wolf, Eckhard; Kupatt, Christian

    2017-01-17

    Diabetes mellitus causes microcirculatory rarefaction and may impair the responsiveness of ischemic myocardium to proangiogenic factors. This study sought to determine whether microvascular destabilization affects organ function and therapeutic neovascularization in diabetes mellitus. The authors obtained myocardial samples from patients with end-stage heart failure at time of transplant, with or without diabetes mellitus. Diabetic (db) and wild-type (wt) pigs were used to analyze myocardial vascularization and function. Chronic ischemia was induced percutaneously (day 0) in the circumflex artery. At day 28, recombinant adeno-associated virus (rAAV) (5 × 10(12) viral particles encoding vascular endothelial growth factor-A [VEGF-A] or thymosin beta 4 [Tβ4]) was applied regionally. CD31+ capillaries per high power field (c/hpf) and NG2+ pericyte coverage were analyzed. Global myocardial function (ejection fraction [EF] and left ventricular end-diastolic pressure) was assessed at days 28 and 56. Diabetic human myocardial explants revealed capillary rarefaction and pericyte loss compared to nondiabetic explants. Hyperglycemia in db pigs, even without ischemia, induced capillary rarefaction in the myocardium (163 ± 14 c/hpf in db vs. 234 ± 8 c/hpf in wt hearts; p < 0.005), concomitant with a distinct loss of EF (44.9% vs. 53.4% in nondiabetic controls; p < 0.05). Capillary density further decreased in chronic ischemic hearts, as did EF (both p < 0.05). Treatment with rAAV.Tβ4 enhanced capillary density and maturation in db hearts less efficiently than in wt hearts, similar to collateral growth. rAAV.VEGF-A, though stimulating angiogenesis, induced neither pericyte recruitment nor collateral growth. As a result, rAAV.Tβ4 but not rAAV.VEGF-A improved EF in db hearts (34.5 ± 1.4%), but less so than in wt hearts (44.8 ± 1.5%). Diabetes mellitus destabilized microvascular vessels of the heart, affecting the amplitude of therapeutic neovascularization via r

  15. Recognition of Fibrotic Infarct Density by the Pattern of Local Systolic-Diastolic Myocardial Electrical Impedance

    PubMed Central

    Amorós-Figueras, Gerard; Jorge, Esther; García-Sánchez, Tomás; Bragós, Ramón; Rosell-Ferrer, Javier; Cinca, Juan

    2016-01-01

    Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1–1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (<10% fibrosis), heterogeneous scar (10–50%) and dense scar (>50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 Ω·cm vs. 10 ± 1 Ω·cm, at 41 kHz; P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions (285 ± 10 Ω·cm, 225 ± 25 Ω·cm, and 162 ± 6 Ω·cm, at 41 kHz; P < 0.001 respectively). Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis (resistivity: r = 0.86 at 1 kHz, P < 0.001; phase angle: r = 0.84 at 41 kHz, P < 0.001). Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of myocardial fibrosis can be detected in vivo by local measurement of phasic systolic

  16. Coronary collateral vessels in patients with previous myocardial infarction

    SciTech Connect

    Nakatsuka, M.; Matsuda, Y.; Ozaki, M.; Ogawa, H.; Moritani, K.; Khono, M.; Miura, T.; Shimizu, T.; Furutani, Y.; Kusukawa, R.

    1987-12-01

    To assess the degree of collateral vessels after myocardial infarction, coronary angiograms, left ventriculograms, and exercise thallium-201 myocardial scintigrams of 36 patients with previous myocardial infarction were reviewed. All 36 patients had total occlusion of infarct-related coronary artery and no more than 70% stenosis in other coronary arteries. In 19 of 36 patients with transient reduction of thallium-201 uptake in the infarcted area during exercise (Group A), good collaterals were observed in 10 patients, intermediate collaterals in 7 patients, and poor collaterals in 2 patients. In 17 of 36 patients without transient reduction of thallium-201 uptake in the infarcted area during exercise (Group B), good collaterals were seen in 2 patients, intermediate collaterals in 7 patients, and poor collaterals in 8 patients (p less than 0.025). Left ventricular contractions in the infarcted area were normal or hypokinetic in 10 patients and akinetic or dyskinetic in 9 patients in Group A. In Group B, 1 patient had hypokinetic contraction and 16 patients had akinetic or dyskinetic contraction (p less than 0.005). Thus, patients with transient reduction of thallium-201 uptake in the infarcted area during exercise had well developed collaterals and preserved left ventricular contraction, compared to those in patients without transient reduction of thallium-201 uptake in the infarcted area during exercise. These results suggest that the presence of viable myocardium in the infarcted area might be related to the degree of collateral vessels.

  17. Noninvasive quantification of the extent of jeopardized myocardium in patients with single-vessel coronary disease by stress thallium-201 single-photon emission computerized rotational tomography

    SciTech Connect

    Prigent, F.; Maddahi, J.; Garcia, E.; Van Train, K.; Friedman, J.; Berman, D.

    1986-03-01

    In 22 patients with single-vessel coronary artery disease and no history of infarction, stress Tl-201 rotational tomography was used to quantify the extent of jeopardized myocardium. The vertical long- and short-axis tomograms were quantified by means of maximum-count circumferential profile analysis. The scintigraphic extent of jeopardized myocardium was expressed as the percentage of profile points falling 2.5 standard deviations below a previously established mean normal profile and was correlated to a quantitatively expressed angiographic extent of jeopardized myocardium. The extent of jeopardized myocardium varied from 1% to 55% by tomography and 8% to 50% by angiography and correlated with an r = 0.79 and a 10% standard error of the estimate. Defect intensity, reflecting the mean depth by which the abnormal points fell below the normal value of greater than or equal to 10%, was 100% specific for a coronary stenosis of greater than or equal to 70%. In conclusion, this study demonstrates that: patients with single-vessel disease have highly variable extents of hypoperfused myocardium defined by Tl-201 tomography and coronary arteriography, there is a fair relationship between angiographic jeopardy score and perfusion defects by Tl-201 tomography during exercise, and Tl-201 tomography may be used to noninvasively determine the extent of hypoperfused myocardium in coronary artery disease.

  18. Association of periprocedural myocardial infarction with long-term survival in patients treated with coronary revascularization therapy of chronic total occlusion.

    PubMed

    Jang, Woo Jin; Yang, Jeong Hoon; Choi, Seung-Hyuk; Song, Young Bin; Hahn, Joo-Yong; Kim, Wook Sung; Lee, Young Tak; Kim, Bum-Sung; Gwon, Hyeon-Cheol

    2016-05-01

    To evaluate the impact of periprocedural myocardial infarction (PMI) on long-term survival after coronary revascularization in patients with chronic total occlusion (CTO). Little is known about the clinical impact of PMI on long-term cardiac mortality after CTO revascularization in patients with stable angina. We analyzed data from 927 patients with CTO and stable angina who were treated with coronary artery bypass grafting (CABG, n = 367) or percutaneous coronary intervention (PCI, n = 560). PMI was defined as a peak CK-MB ≥ 3 times the upper limit of normal (ULN) after PCI or a CK-MB ≥ 5 times the ULN after CABG. The primary outcome was cardiac death in patients with PMI (PMI group, n = 118 [12.7%]) or without PMI (no-PMI group, n = 809 [87.3%]) after revascularization. During a median follow-up of 42 months, PMI occurred in 118 patients (12.7% of the overall study population). Fifty-nine patients treated with PCI (10.5% of PCI subgroup) and 59 patients treated with CABG (16.1% of CABG subgroup) suffered from PMI. In multivariate analysis, the PMI group and the no-PMI group had a similar incidence of cardiac death (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.20 to 1.62; P = 0.29). PMI may not be associated with increased cardiac mortality after coronary revascularization in patients with stable CTO. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  19. Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction: Early Evidence.

    PubMed

    Cokic, Ivan; Kali, Avinash; Yang, Hsin-Jung; Yee, Raymond; Tang, Richard; Tighiouart, Mourad; Wang, Xunzhang; Jackman, Warren S; Chugh, Sumeet S; White, James A; Dharmakumar, Rohan

    2015-08-01

    Recent canines studies have shown that iron deposition within chronic myocardial infarction (CMI) influences the electric behavior of the heart. To date, the link between the iron deposition and malignant ventricular arrhythmias in humans with CMI is unknown. Patients with CMI (n=94) who underwent late-gadolinium-enhanced cardiac magnetic resonance imaging before implantable cardioverter-defibrillator implantation for primary and secondary preventions were retrospectively analyzed. The predictive values of hypointense cores (HIC) in balanced steady-state free precession images and conventional cardiac magnetic resonance imaging and ECG malignant ventricular arrhythmia parameters for the prediction of primary combined outcome (appropriate implantable cardioverter-defibrillator therapy, survived cardiac arrest, or sudden cardiac death) were studied. The use of HIC within CMI on balanced steady-state free precession as a marker of iron deposition was validated in a canine MI model (n=18). Nineteen patients met the study criteria with events occurring at a median of 249 (interquartile range of 540) days after implantable cardioverter-defibrillator placement. Of the 19 patients meeting the primary end point, 18 were classified as HIC+, whereas only 1 was HIC-. Among the cohort in whom the primary end point was not met, there were 28 HIC+ and 47 HIC- patients. Receiver operating characteristic curve analysis demonstrated an additive predictive value of HIC for malignant ventricular arrhythmias with an increased area under the curve of 0.87 when added to left ventricular ejection fraction (left ventricular ejection fraction alone, 0.68). Both cardiac magnetic resonance imaging and histological validation studies performed in canines demonstrated that HIC regions in balanced steady-state free precession images within CMI likely result from iron depositions. Hypointense cores within CMI on balanced steady-state free precession cardiac magnetic resonance imaging can be used

  20. Impact of chronic obstructive pulmonary disease on in-hospital morbidity and mortality in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

    PubMed

    Șerban, Răzvan Constantin; Hadadi, Laszlo; Șuș, Ioana; Lakatos, Eva Katalin; Demjen, Zoltan; Scridon, Alina

    2017-09-15

    Patients with chronic obstructive pulmonary disease (COPD) presenting with ST-segment elevation myocardial infarction (STEMI) are less likely to beneficiate of primary percutaneous coronary intervention (pPCI), and have poorer prognosis. We aimed to evaluate the impact of COPD on the in-hospital outcomes of pPCI-treated STEMI patients. Data were collected from 418 STEMI patients treated by pPCI. Inotropics and diuretics usage, cardiogenic shock, asystole, kidney dysfunction, and left ventricular ejection fraction were used as markers of hemodynamic complications. Atrial and ventricular fibrillation, conduction disorders, and antiarrhythmics usage were used as markers of arrhythmic complications. In-hospital mortality was evaluated. The associations between these parameters and COPD were assessed. COPD was present in 7.42% of STEMI patients. COPD patients were older (p=0.02) and less likely to receive beta-blockers (OR 0.29; 95%CI 0.13-0.64; p<0.01). They had higher Killip class on admission (p<0.001), received more often inotropics (p<0.001) and diuretics (p<0.01), and presented more often atrial (p=0.01) and ventricular fibrillation (p=0.02). Unadjusted in-hospital mortality was higher in COPD patients (OR 4.18, 95%CI 1.55-11.30, p<0.01). After adjustment for potentially confounding factors except beta-blockers, COPD remained an independent predictor of in-hospital mortality (p=0.02). After further adjustment with beta-blocker therapy, no excess mortality was noted in COPD patients. Despite being treated by pPCI, COPD patients with STEMI are more likely to develop hemodynamic and arrhythmic complications, and have higher in-hospital mortality. This appears to be due to lower beta-blockers usage in COPD patients. Increasing beta-blockers usage in COPD patients with STEMI may improve survival. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. Caudate infarcts.

    PubMed

    Caplan, L R; Schmahmann, J D; Kase, C S; Feldmann, E; Baquis, G; Greenberg, J P; Gorelick, P B; Helgason, C; Hier, D B

    1990-02-01

    Eighteen patients had caudate nucleus infarcts (10 left-sided; 8 right-sided). Infarcts extended into the anterior limb of the internal capsule in 9 patients, and also the anterior putamen in 5 patients. Thirteen patients had motor signs, most often a slight transient hemiparesis. Dysarthria was common (11 patients). Cognitive and behavioral abnormalities were frequent, and included abulia (10 patients), agitation and hyperactivity (7 patients), contralateral neglect (3 patients, all right caudate), and language abnormalities (2 patients, both left caudate). The majority of patients had risk factors for penetrating artery disease. Branch occlusion of Heubner's artery, or perforators from the proximal anterior or middle cerebral arteries were the posited mechanism of infarction.

  2. Characterization of acute myocardial infarction by magnetic resonance imaging.

    PubMed

    Johnston, D L; Wendt, R E; Mulvagh, S L; Rubin, H

    1992-05-15

    The T2-weighted spin-echo technique is currently the most frequently used magnetic resonance imaging (MRI) method to visualize acute myocardial infarction. However, image quality is often degraded by ghost artifacts from blood flow, and respiratory and cardiac contractile motion. To enhance the usefulness of this technique for detailed characterization of infarction, a velocity-compensated spin-echo pulse sequence was tested by imaging a flow phantom, 6 normal subjects and 17 patients with acute myocardial infarction. After preliminary studies were performed in 7 patients to determine optimal imaging parameters, a standardized imaging protocol was used in the next 10. The location of myocardial infarction identified by the electrocardiogram and coronary anatomy was correctly identified in 10 of 10 patients. Distribution of the injury within the left ventricle was clearly visualized, and showed that patients often had a mixture of transmural and nontransmural injury. Heterogenous distribution of signal intensity within the infarction suggested the presence of hemorrhage. Papillary muscle involvement was readily apparent. Signal intensity of the infarction (brightest segment) was increased by 89 +/- 31% compared with the mean of the remote segments. The myocardial/skeletal muscle ratio was significantly (p less than 0.001) increased for the infarction segments compared with that for remote myocardium, allowing quantitative analysis of segmental signal intensity. The MRI wall motion study obtained as part of this protocol demonstrated wall thickening in 58% of the infarction segments and in 6 of 10 patients. This finding suggested the presence of reversibly injured myocardium. In conclusion, the results demonstrate the potential of MRI for detailed tissue characterization after acute myocardial infarction.

  3. Acute myocardial infarction.

    PubMed

    Boersma, Eric; Mercado, Nestor; Poldermans, Don; Gardien, Martin; Vos, Jeroen; Simoons, Maarten L

    2003-03-08

    Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view. The advent of coronary-care units and the results of randomised clinical trials on reperfusion therapy, lytic or percutaneous coronary intervention, and chronic medical treatment with various pharmacological agents have substantially changed the therapeutic approach, decreased in-hospital mortality, and improved the long-term outlook in survivors of the acute phase. New treatments will continue to emerge, but the greatest challenge will be to effectively implement preventive actions in all high-risk individuals and to expand delivery of acute treatment in a timely fashion for all eligible patients.

  4. Effects of coronary occlusion and norepinephrine on the myocardium of alloxan-diabetic dogs.

    PubMed

    Palik, I; Koltai, M Z; Kolonics, I; Wagner, M; Pogátsa, G

    1982-01-01

    The aim of this study was to clarify the role of altered diabetic vascular reactivity in ischaemic heart disease. In diabetic condition, the necrotic area of myocardial infarction was significantly extended and myocardial oedema failed to develop after administration of norepinephrine 2 or 48 hours after ligation of the left anterior descending coronary artery. In metabolically healthy dogs the necrotic area of myocardial infarction was considerably smaller and an increase in myocardial water content, in myocardial thiocyanate space, in microscopically demonstrable permeability and in diastolic stiffness of left ventricular wall occurred when norepinephrine was administered 2 or 48 hours after coronary infarction. A close correlation was demonstrable between enhanced water content, thiocyanate space and diastolic stiffness in metabolically healthy animals, whereas in diabetic condition diastolic stiffness was primarily increased, and decreased when norepinephrine was infused after coronary ligation. Therefore, the altered vascular reactivity in diabetes is supposed to be responsible for the lack of oedema in the nonischaemic part of myocardium after norepinephrine infusion as well as for the size and severity of myocardial infarction.

  5. Effect of ethanol and the catalase inhibitor aminotriazole on lipid peroxidation in the rat myocardium

    SciTech Connect

    Panchenko, L.F.; Pirozhkov, S.V.; Popova, S.V.; Antonenkov, V.D.

    1987-09-01

    The authors study the effect of chronic administration of ethanol and aminotriazole on the level of lipid peroxidation in the ray myocardium. The action of natural and artificial antioxidants on alcohol-induced lipid peroxidation also was studied. To determine the level of chemiluminescence, 1 ml of a sample of nuclear free homogenate or of the total fraction of particles was introduced for radioactivity measurement. After incubation the spontaneous weak luminescence was measured.

  6. Chitosan hydrogel improves mesenchymal stem cell transplant survival and cardiac function following myocardial infarction in rats

    PubMed Central

    Xu, Bin; Li, Yang; Deng, Bo; Liu, Xiaojing; Wang, Lin; Zhu, Qing-Lei

    2017-01-01

    Myocardial infarction (MI) remains the leading cause of cardiovascular-associated mortality and morbidity. Improving the retention rate, survival and cardiomyocyte differentiation of mesenchymal stem cells (MSCs) is important in improving the treatment of patients with MI. In the present study, temperature-responsive chitosan hydrogel, an injectable scaffold, was used to deliver MSCs directly into the infarcted myocardium of rats following MI. Histopathology and immunohistochemical staining were used to evaluate cardiac cell survival and regeneration, and cardiac function was assessed using an echocardiograph. It was demonstrated that chitosan hydrogel increased graft size and cell retention in the ischemic heart, promoted MSCs to differentiate into cardiomyocytes and increased the effects of MSCs on neovasculature formation. Furthermore, chitosan hydrogel enhanced the effect of MSCs on the improvement of cardiac function and hemodynamics in the infarcted area of rats following MI. These findings suggest that chitosan hydrogel is an appropriate material to deliver MSCs into infarcted myocardium. PMID:28352335

  7. Vegfa Impacts Early Myocardium Development in Zebrafish

    PubMed Central

    Zhu, Diqi; Fang, Yabo; Gao, Kun; Shen, Jie; Zhong, Tao P.; Li, Fen

    2017-01-01

    Vascular endothelial growth factor A (Vegfa) signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium–endocardium crosstalk. PMID:28230770

  8. Automatic cardiac MRI myocardium segmentation using graphcut

    NASA Astrophysics Data System (ADS)

    Kedenburg, Gunnar; Cocosco, Chris A.; Köthe, Ullrich; Niessen, Wiro J.; Vonken, Evert-jan P. A.; Viergever, Max A.

    2006-03-01

    Segmentation of the left myocardium in four-dimensional (space-time) cardiac MRI data sets is a prerequisite of many diagnostic tasks. We propose a fully automatic method based on global minimization of an energy functional by means of the graphcut algorithm. Starting from automatically obtained segmentations of the left and right ventricles and a cardiac region of interest, a spatial model is constructed using simple and plausible assumptions. This model is used to learn the appearance of different tissue types by non parametric robust estimation. Our method does not require previously trained shape or appearance models. Processing takes 30-40s on current hardware. We evaluated our method on 11 clinical cardiac MRI data sets acquired using cine balanced fast field echo. Linear regression of the automatically segmented myocardium volume against manual segmentations (performed by a radiologist) showed an RMS error of about 12ml.

  9. Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

    PubMed

    Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

    2017-05-09

    Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

  10. Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab

    SciTech Connect

    Khaw, B.A.; Yasuda, T.; Gold, H.K.; Leinbach, R.C.; Johns, J.A.; Kanke, M.; Barlai-Kovach, M.; Strauss, H.W.; Haber, E.

    1987-11-01

    Indium-111 monoclonal antimyosin Fab scintigraphy was used to detect myocardial necrosis in 52 of 54 patients (96.3%) with acute myocardial infarction. Infarcts were visualized when coronary arteries were persistently occluded (n = 10), became patent after thrombolysis (n = 33), or became patent after spontaneous reperfusion (n = 7). Posteroinferolateral visualizations were obtained in two patients with clinical and enzymatic evidence of infarction but normal electrocardiograms. Of the two patients in whom no infarcts were visualized, one had an anterior myocardial infarct. This patient underwent successful thrombolytic therapy, with attendant minimization of creatine kinase release. The other patient had a small, nonreperfused inferior myocardial infarct. Five patients with a history of remote infarction and acute necrosis showed antimyosin uptake only in regions concordant with the acute episodes of infarction, and radiolabeled antimyosin Fab localized in neither old infarcts nor normal, noninfarcted myocardium. Antimyosin Fab scintigraphy, thus, appears to be a highly specific means of delineating necrotic myocardium, at least in this limited and selected group of patients.

  11. Mechanisms of myocardium-coronary vessel interaction

    PubMed Central

    Algranati, Dotan; Kassab, Ghassan S.

    2010-01-01

    The mechanisms by which the contracting myocardium exerts extravascular forces (intramyocardial pressure, IMP) on coronary blood vessels and by which it affects the coronary flow remain incompletely understood. Several myocardium-vessel interaction (MVI) mechanisms have been proposed, but none can account for all the major flow features. In the present study, we hypothesized that only a specific combination of MVI mechanisms can account for all observed coronary flow features. Three basic interaction mechanisms (time-varying elasticity, myocardial shortening-induced intracellular pressure, and ventricular cavity-induced extracellular pressure) and their combinations were analyzed based on physical principles (conservation of mass and force equilibrium) in a realistic data-based vascular network. Mechanical properties of both vessel wall and myocardium were coupled through stress analysis to simulate the response of vessels to internal blood pressure and external (myocardial) mechanical loading. Predictions of transmural dynamic vascular pressure, diameter, and flow velocity were determined under each MVI mechanism and compared with reported data. The results show that none of the three basic mechanisms alone can account for the measured data. Only the combined effect of the cavity-induced extracellular pressure and the shortening-induced intramyocyte pressure provides good agreement with the majority of measurements. These findings have important implications for elucidating the physical basis of IMP and for understanding coronary phasic flow and coronary artery and microcirculatory disease. PMID:19966048

  12. High-resolution 3-D T1*-mapping and quantitative image analysis of GRAY ZONE in chronic fibrosis.

    PubMed

    Pop, Mihaela; Ramanan, Venkat; Yang, Franklin; Zhang, Li; Newbigging, Susan; Ghugre, Nilesh R; Wright, Graham A

    2014-12-01

    The substrate of potentially lethal cardiac arrhythmias often resides in the gray zone (GZ), a mixture of viable myocytes and collagen strands found between healthy myocardium and infarct core (IC). The specific aims of this paper are to demonstrate correspondence between regions delineated in T1* (apparent T1) maps and tissue characteristics seen in histopathology and to determine the MR imaging resolution needed to adequately identify GZ-associated substrate in chronic infarct. For this, a novel 3-D multicontrast late enhancement (MCLE) MR method was used to image ex vivo swine hearts with chronic infarction, at high resolution ( 0.6×0.6×1.25 mm). Pixel-wise classified tissue maps were calculated using steady-state and T1* images as input to a fuzzy-clustering algorithm. Quantitative histology based on collagen stains was performed in n = 10 selected slabs and showed very good correlations between histologically-determined areas of heterogeneous and dense fibrosis, and the corresponding GZ ( R2 = 0.96) and IC ( R2 = 0.97 ) in tissue classified maps. Furthermore, in n = 24 slabs, we performed volumetric measurements of GZ and IC, at the original and decreased image resolutions. Our results demonstrated that the IC volume remained relatively unchanged across all resolutions, whereas the GZ volume progressively increased with diminished image resolution, with changes reaching significance at 1×1×5 mm resolution (p < 0.05 ) but not at 1×1×2.5 mm, suggesting that this resolution may be sufficient to adequately identify the GZ from MCLE images, enabling an effective MR probing of remodeled myocardium in late infarct. Future work will focus on translating these findings to optimizing the current in vivo MCLE imaging of the GZ.

  13. [Myocardial infarction after butane inhalation in a 14-year-old boy].

    PubMed

    Godlewski, Krzysztof; Werner, Bozena; Sterliński, Maciej; Pytkowski, Mariusz; Szwed, Hanna; Domagała, Marek; Koc, Lucyna

    2006-03-01

    Myocardial infarction is a rare disease in children. Among many reasons the toxic damage of myocardium should be taken into consideration. The authors present the case of a 14-year-old boy with sudden cardiac arrest due to ventricular fibrillation and myocardial infarction as a result of butane gas inhalation. Coronary angiography revealed normal coronary arteries. Cardioverter-defibrillator was implanted as a secondary prophylaxis of sudden cardiac death.

  14. Noninvasive computational imaging of cardiac electrophysiology for 3-D infarct.

    PubMed

    Wang, Linwei; Wong, Ken C L; Zhang, Heye; Liu, Huafeng; Shi, Pengcheng

    2011-04-01

    Myocardial infarction (MI) creates electrophysiologically altered substrates that are responsible for ventricular arrhythmias, such as tachycardia and fibrillation. The presence, size, location, and composition of infarct scar bear significant prognostic and therapeutic implications for individual subjects. We have developed a statistical physiological model-constrained framework that uses noninvasive body-surface-potential data and tomographic images to estimate subject-specific transmembrane-potential (TMP) dynamics inside the 3-D myocardium. In this paper, we adapt this framework for the purpose of noninvasive imaging, detection, and quantification of 3-D scar mass for postMI patients: the framework requires no prior knowledge of MI and converges to final subject-specific TMP estimates after several passes of estimation with intermediate feedback; based on the primary features of the estimated spatiotemporal TMP dynamics, we provide 3-D imaging of scar tissue and quantitative evaluation of scar location and extent. Phantom experiments were performed on a computational model of realistic heart-torso geometry, considering 87 transmural infarct scars of different sizes and locations inside the myocardium, and 12 compact infarct scars (extent between 10% and 30%) at different transmural depths. Real-data experiments were carried out on BSP and magnetic resonance imaging (MRI) data from four postMI patients, validated by gold standards and existing results. This framework shows unique advantage of noninvasive, quantitative, computational imaging of subject-specific TMP dynamics and infarct mass of the 3-D myocardium, with the potential to reflect details in the spatial structure and tissue composition/heterogeneity of 3-D infarct scar.

  15. Backscatter and attenuation characterization of ventricular myocardium

    NASA Astrophysics Data System (ADS)

    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when

  16. Rehmannia Glutinosa Extract Activates Endothelial Progenitor Cells in a Rat Model of Myocardial Infarction through a SDF-1 α/CXCR4 Cascade

    PubMed Central

    Wang, Ying-Bin; Liu, Yun-Fang; Lu, Xiao-Ting; Yan, Fang-Fang; Wang, Bo; Bai, Wen-Wu; Zhao, Yu-Xia

    2013-01-01

    Objectives Endothelial progenitor cells (EPCs) can be used to repair tissues after myocardial infarction (MI) but EPC activators have adverse reactions. Rehmannia glutinosa is a herb used in traditional Chinese medicine, which can promote bone-marrow proliferation and protect the ischemic myocardium. We investigated the effects of Rehmannia glutinosa extract (RGE) on EPCs in a rat model of MI. Methods A total of 120 male Wistar rats were randomized to 2 groups (n = 60 each) for treatment: high-dose RGE (1.5 g·kg−1·day−1 orally) for 8 weeks, then left anterior descending coronary artery ligation, mock surgery or no treatment, then RGE orally for 4 weeks; or normal saline (NS) as the above protocol. The infarct region of the left ventricle was assessed by serial sectioning and morphology. EPCs were evaluated by number and function. Protein and mRNA levels of CD133, vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-X-C motif receptor 4 (CXCR4), stromal cell–derived factor-1α (SDF-1α) were measured by immunohistochemistry, Western blot and quantitative PCR analysis. Results RGE significantly improved left ventricular function, decreased the ischemic area and the apoptotic index in the infarct myocardium, also decreased the concentration of serum cardiac troponin T and brain natriuretic peptide at the chronic stage after MI (from week 2 to week 4). RGE increased EPC number, proliferation, migration and tube-formation capacity. It was able to up-regulate the expression of angiogenesis-associated ligand/receptor, including CD133, VEGFR2 and SDF-1α/CXCR4. In vitro, the effect of RGE on SDF-1α/CXCR4 cascade was reversed by the CXCR4 specific antagonist AMD3100. Conclusion RGE may enhance the mobilization, migration and therapeutic angiogenesis of EPCs after MI by activating the SDF-1α/CXCR4 cascade. PMID:23349848

  17. Interval and continuous aerobic exercise training similarly increase cardiac function and autonomic modulation in infarcted mice.

    PubMed

    Abad, Cesar Cavinato Cal; do Nascimento, Ademir Manuel; Dos Santos, Leandro Eziquiel; Figueroa, Diego; Ramona, Pamella; Sartori, Michele; Scapini, Katia B; Albuquerque, Oscar; Moraes-Silva, Ivana Cinthya; Coelho-Júnior, Hélio José; Rodrigues, Bruno; Mostarda, Cristiano Teixeira; De Angelis, Kátia; Irigoyen, Maria Cláudia

    2017-06-01

    The present study aimed to compare the effects of moderate-intensity continuous and high-intensity interval exercise training (ET) on exercise tolerance, cardiac morphometry and function, hemodynamic, and cardiac autonomic modulation in myocardial infarcted mice. Wild-type mice (WT) were divided into four groups: sedentary WT (S); WT myocardium infarction sedentary (IS); WT myocardium infarction underwent to moderate-intensity continuous ET (MICT), and WT myocardium infarction underwent to high-intensity interval ET (MIIT). After 60 days of descending coronary artery ligation, moderate-intensity continuous ET consisted of running at 60% of maximum, while the high-intensity interval training consisted of eight sprints of 4 min at 80% of maximum and a 4-min recovery at 40% of maximum. Both exercises were performed 1 hr a day, 5 days a week, during 8 weeks. Results demonstrated that IS showed elevated exercise tolerance, as well as decreased hemodynamic and heart function, and autonomic control. On the other hand, both programs of ET were equally effective to increase all parameters, without further differences between the groups. In conclusion, the results of the present study showed that myocardial infarction leads to damage in both investigated strains and the two types of physical exercise attenuated the major impairments provoked by myocardial infarction in exercise tolerance, cardiac structure, cardiac function, hemodynamic and cardiac autonomic modulation.

  18. [Use of cytoflavin for correction of complications of myocardial infarction].

    PubMed

    Bul'on, V V; Khnychenko, L K; Sapronov, N S; Kovalenko, A L; Alekseeva, L E

    2002-01-01

    The possibility of using a combined preparation cytoflavine was studied on rats with myocardial infarction induced by coronary artery occlusion. The drug produces a positive action upon the energy exchange and the lipid peroxidation process and normalizes functioning of the system of antioxidant protection of the ischemized myocardium. Cytoflavine treatment led to a more favorable course of ischemic and necrotic processes and optimum organization of the necrosis zones.

  19. The impact of the location of a chronic total occlusion in a non-infarct-related artery on long-term mortality in ST-elevation myocardial infarction patients.

    PubMed

    Hoebers, Loes P C; Elias, Joëlle; van Dongen, Ivo M; Ouweneel, Dagmar M; Claessen, Bimmer E P M; Piek, Jan J; Henriques, Jose P S

    2016-07-20

    Several studies have evaluated the impact of a CTO on short- and long-term mortality in STEMI patients. It has been speculated that the adverse effect on prognosis could differ per coronary location. The purpose of this study was to evaluate whether the long-term prognosis of STEMI patients differs according to the coronary location of the CTO. Between 2000 and 2012, a total of 480 STEMI patients with a CTO in a non-infarct-related artery were included. The primary outcome for the present analysis was three-year all-cause mortality, evaluating the impact of the coronary CTO and infarct location. Four hundred and thirteen patients had a single CTO in a non-infarct-related artery, whereas 67 patients had more than one CTO and in this group mortality was higher. In patients with a single CTO, the highest risk of mortality was observed when the culprit lesion was located in the LAD or proximal LCX or when the CTO lesion was located in the proximal LAD. We previously reported that STEMI patients with a CTO have a worse prognosis than STEMI patients without a CTO. We now show that, in these patients, LAD or proximal LCX location for the culprit lesion, or proximal LAD location for the CTO lesion, is associated with the highest risk. As a result, almost all CTO patients are at increased risk for mortality due to the combination of the culprit and CTO artery location.

  20. Sequential thallium-201 myocardial scintigraphy after acute infarction in man

    SciTech Connect

    Fletcher, J.W.; Mueller, H.S.; Rao, P.S.

    1980-07-01

    Three sequential Tl-201 myocardial perfusion studies were performed in 21 patients (18 men, 3 women) with first acute transmural myocardia infarction. The Tl-201 image defect size was determined with a semiquantitative visual scoring method and temporal changes in image defect size were compared to CK-MB infarct size and enzymatic evidence of progressive myocardial necrosis and infarct extension. Progressive decreases in Tl-201 image defect size were observed and the visual score in all 21 patients decreased significantly from 6.5 +- 3.7 (mean +- SD) on day 1 to 4.9 +- 3.5 on day 12. Eleven patients without evidence of infarct extension had significantly lower infarct size, a significant decrease in visual score by the 12th day and had significantly smaller Tl-201 defects at all three study times compared to 10 patients with infarct extension. Seven of 10 (70%) with extension had an initial visual score greater than or equal to 7 compared to only 2/11 (18%) without extension. The temporal behavior of Tl-201 image defects is related to the size of the infarction and presence or absence of extension. Sequential studies comparing early initial and subsequent defect size may assist in evaluating the behavior of ischemic and infarcted myocardium in the postinfarction period.

  1. Cardiac Extracellular Vesicles in Normal and Infarcted Heart

    PubMed Central

    Chistiakov, Dimitry A.; Orekhov, Alexander N.; Bobryshev, Yuri V.

    2016-01-01

    Heart is a complex assembly of many cell types constituting myocardium, endocardium and epicardium that intensively communicate to each other in order to maintain the proper cardiac function. There are many types of intercellular intracardiac signals, with a prominent role of extracellular vesicles (EVs), such as exosomes and microvesicles, for long-distant delivering of complex messages. Cardiomyocytes release EVs, whose content could significantly vary depending on the stimulus. In stress, such as hypoxia, inflammation or injury, cardiomyocytes increase secretion of EVs. In hypoxic conditions, cardiac EVs are enriched with angiogenic and prosurvival factors. In acute myocardial infarction (AMI), damaged cardiac muscle cells produce EVs with increased content of angiogenic, anti-apoptotic, mitogenic and growth factors in order to induce repair and healing of the infarcted myocardium. Exosomal microRNAs play a central role in cardiac regeneration. In AMI, circulating cardiac EVs abundantly contain cardiac-specific miRNAs that serve as indicators of cardiac damage and have a big diagnostic potential as AMI biomarkers. Cardioprotective and regenerative properties of exosomes derived from cardiac and non-cardiac stem/progenitor cells are very helpful to be used in cell-free cardiotherapy and regeneration of post-infarct myocardium. PMID:26742038

  2. Testosterone replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing expression of cytokines HIF-1a, SDF-1a and VEGF.

    PubMed

    Chen, Yeping; Fu, Lu; Han, Ying; Teng, Yueqiu; Sun, Junfeng; Xie, Rongsheng; Cao, Junxian

    2012-06-05

    In order to investigate the effects of testosterone-replacement therapy on peripheral blood stem cells and angiogenesis after acute myocardial infarction, a castrated rat acute myocardial infarction model was established by ligation of the left anterior descending coronary followed by treatment with testosterone. CD34(+) cells in myocardium and in peripheral blood after 1 and 3 days were measured by immunohistochemistry and flow cytometry, respectively. In the early phase of acute myocardial infarction, the expression levels of hypoxia-inducible factor 1a (HIF-1a), stromal cell-derived factor 1a (SDF-1a) and vascular endothelium growth factor (VEGF) in ischemic myocardium were determined by real time RT-PCR and immunohistochemistry, respectively. Infarct size, cardiomyocyte apoptosis, capillary density and cardiac function were assessed after 28 days. These results showed that the number of CD34(+) cells in the peripheral blood and in myocardium was significantly decreased in castrated rats, and the early expression levels of HIF-1a, SDF-1a and VEGF in the myocardium were also decreased. Furthermore, reduced capillary density, worsened cardiac function, increased infarct size and cardiomyocyte apoptosis at 28 days post-infarction were found in castrated rats. But these adverse effects could be reversed by testosterone-replacement therapy. These findings suggested that testosterone can increase the mobilization and homing of CD34(+) cells into the ischemic myocardium and further promote neoangiogenesis after myocardial infarction. The pro-angiogenesis effect of testosterone-replacement therapy is associated with the enhanced expression of HIF-1a, SDF-1a and VEGF in myocardium after myocardial infarction.

  3. Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis

    PubMed Central

    Rothnie, Kieran J; Yan, Ruoling; Smeeth, Liam; Quint, Jennifer K

    2015-01-01

    Objectives Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD. Design Systematic review and meta-analysis. Methods MEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible. Results Searches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case–control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40). Conclusions There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI. PMID:26362660

  4. Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis.

    PubMed

    Rothnie, Kieran J; Yan, Ruoling; Smeeth, Liam; Quint, Jennifer K

    2015-09-11

    Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD. Systematic review and meta-analysis. MEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible. Searches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case-control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40). There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Metabolic tissue characterization in patients with acute myocardial infarction with positron tomography

    SciTech Connect

    Schwaiger, M.; Brunken, R.C.; Grover-McKay, M.; Krivokapich, J.; Child, J.S.; Tillisch, J.H.; Marshall, R.C.; Phelps, M.E.; Schelbert, H.R.

    1985-05-01

    Identification of myocardium at risk in acute myocardial infarction (AMI) is important for patient management. The authors previously demonstrated in animals that reversible tissue injury can be identified with PET and tracers of metabolism. To characterize reginal metabolism in AMI, 12 patients were studied <72 hours after onset of symptoms with positron tomography (PET). Regional wall motion (WM) was assessed by 2D echocardiography at the time of the PET study and again 6 weeks later. Myocardial blood flow (MBF) and exogenous glucose utilization were measured with N-13 ammonia and F-18 deoxyglucose in 5 LV segments in each patient and compared to regional WM. MBF was decreased in 29 LV segments. The irreversible tissue injury can be identified early in patients with AMI. PET frequently reveals persistent glucose utilization in ''infarcted'' myocardium when studied within 72 hours after AMI. Persistent exogenous glucose utilization detected by PET early after AMI can identify viable but jeopardized myocardium and may predict subsequent functional recovery.

  6. Uptake of iodinated contrast material in ischemic myocardium as an indicator of loss of cellular membrane integrity.

    PubMed

    Abraham, J L; Higgins, C B; Newell, J D

    1980-11-01

    Differential uptake of iodine containing radiographic contrast medium (I) in myocardial infarcts compared with normal mycardium has been detected by computerized transmission tomography (CTT). In this study the histologic and cellular distribution of I in ischemically damaged canine myocardium after intravenous administration of contrast material was examined by the use of scanning electron microscopy and energy dispersive X-ray microanalysis of fresh frozen cryosections. Analysis of individual cells in 6-mu thick sections mounted on carbon substrates showed that I was detectable in the ischemically damaged but not the normal myocardial cells. A decline in the potassium-to-sodium ratio confirmed the loss of membrane integrity in the ischemically damaged cells that accumulated I. These results indicate that I enters ischemically damaged but not normal myocardial cells suggesting that CTT scans after intravenous administration of contrast material may be capable of defining the area of the myocardium in which cells have lost membrane integrity after an ischemic injury.

  7. Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell transplantation repairs ischemic myocardium

    PubMed Central

    Li, Jun; Zhu, Kai; Yang, Shan; Wang, Yulin; Guo, Changfa; Yin, Kanhua; Wang, Chunsheng

    2015-01-01

    Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothelial cells and cardiomyocyte-like differentiation of BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene-modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis, inhibit remodeling, increase grafted cell survival and reduce apoptosis. In conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene modified BMSCs, could promote the histological cardiac repair for a clinically relevant porcine model of I/R myocardium injury. PMID:25767192

  8. Diagnostic accuracy of late iodine-enhancement dual-energy computed tomography for the detection of chronic myocardial infarction compared with late gadolinium-enhancement 3-T magnetic resonance imaging.

    PubMed

    Wichmann, Julian L; Bauer, Ralf W; Doss, Mirko; Stock, Wenzel; Lehnert, Thomas; Bodelle, Boris; Frellesen, Claudia; Vogl, Thomas J; Kerl, J Matthias

    2013-12-01

    The purpose of the study was to compare the performance of late iodine-enhancement (LIE) dual-energy computed tomography (DECT) linear blending and selective myocardial iodine mapping for the detection of chronic myocardial infarction (CMI) with late gadolinium-enhancement (LGE) 3-T magnetic resonance imaging. This study was approved by the institutional review board, and the patients gave informed consent. A total of 20 patients with a history of CMI underwent cardiac LIE-DECT and LGE-MRI. Images of the LIE-DECT were reconstructed as 100 kilovolt (peak) (kV[p]), 140 kV(p), and weighted-average (WA; linear blending) images from low- and high-kilovoltage peak data using 3 different weighting factors (0.8, 0.6, 0.3). Additional color-coded myocardial iodine distribution maps were calculated. The images were reviewed for the presence of late enhancement, transmural extent, signal characteristics, infarct volume, and subjective image quality. Segmental analysis of LIE-DECT data from 100 kV(p), WA of 0.8, and WA of 0.6 showed identical results for the identification of CMI (89% sensitivity, 98% specificity, 96% accuracy) and correctly identified all segments with transmural scarring detected through LGE-MRI. Weighted average of 0.6 received the best subjective image quality rating (15/20 votes) and average measured infarct size correlated best with LGE-MRI (5.7% difference). In comparison with LGE-MRI, iodine distribution maps were susceptible to false-positive and false-negative findings (52% sensitivity, 88% specificity, 81% accuracy), overestimating quantity of transmural scars by 78% while underestimating infarct volume by 55%. Late iodine enhancement cardiac dual-energy computed tomography correlates well with LGE-MRI for detecting CMI, whereas iodine distribution analysis provides inferior accuracy. Linear blending further improves image quality and enables more precise estimation of scar volume.

  9. Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction.

    PubMed

    Garg, Monika; Khanna, Deepa; Kalra, Sanjeev; Balakumar, Pitchai

    2016-10-01

    Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses.

  10. Prolonged Cardiac Dysfunction After Intraparenchymal Hemorrhage and Neurogenic Stunned Myocardium

    PubMed Central

    Krishnamoorthy, Vijay; Wilson, Thomas; Sharma, Deepak; Vavilala, Monica S.

    2015-01-01

    Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Lastly, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients. PMID:26462162

  11. Immunohistochemical Investigation of the Heart Allograft Myocardium (1991-1998).

    PubMed

    Beletskaya, Ludmila V.; Baranova, Flora S.; Khalimova, Zarema A.; Zaidenov, Vladimir A.; Kurenkova, Lubov G.; Kormer, Arkadiy Ya.; Khubutia, Anzor Sh.; Kupriyanova, Anna G.; Shumakov, Valeriy I.

    2000-04-01

    What is a contribution of the humoral (vascular) and mixed type of the rejection episodes to all the episodes of heart allograft rejection is not quite clear, though this factor is of considerable importance for the choice of the treatment methods. The hearts from recipients, as well as endomyocardial biopsies of the heart allografts and postmortem material were investigated with the aim to determine the immunopathological process. Overall, 420 samples from 80 patients were analyzed. Immunofluorescence examination of endomyocardial biopsy showed that in 8 from 44 patients with heart allograft in postoperative period for the first six weeks there were revealed the immunomorphological signs of the acute humoral rejection, manifested as fixation of immunoglobulins and complement in capillaries. Six of them exhibited rejection of mixed type. Most patients in the later postoperative period exhibited a discrete local fixation of immunoglobulins and complement in myocardium, that can be assessed as one of the compartments of the chronic rejection process. In cases of the secondary administration of serum preparations, the fixation of immune complexes was shown in sarcolemma and capillaries, and can be proposed as a sign of serum disease. Repeated acute rejection episodes of humoral or mixed types raised at the first six weeks after transplantation. In the period from 1-5 years after operation, patients displayed discrete deposits of the immunoglobulins and complement as part of the chronic rejection process.

  12. Human cord blood cells and myocardial infarction: effect of dose and route of administration on infarct size.

    PubMed

    Henning, Robert J; Burgos, Jose D; Vasko, Mark; Alvarado, Felipe; Sanberg, Cyndy D; Sanberg, Paul R; Morgan, Michael B

    2007-01-01

    There is no consensus regarding the optimal dose of stem cells or the optimal route of administration for the treatment of acute myocardial infarction. Bone marrow cells, containing hematopoietic and mesenchymal stem cells, in doses of 0.5 x 10(6) to >30 x 10(6) have been directly injected into the myocardium or into coronary arteries or infused intravenously in subjects with myocardial infarctions to reduce infarct size and improve heart function. Therefore, we determined the specific effects of different doses of human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic and mesenchymal stem cells, on infarct size. In order to determine the optimal technique for stem cell administration, HUCBC were injected directly into the myocardium (IM), or into the LV cavity with the ascending aorta transiently clamped to facilitate coronary artery perfusion (IA), or injected intravenously (IV) in rats 1-2 h after the left anterior coronary artery was permanently ligated. Immune suppressive therapy was not given to any rat. One month later, the infarct size in control rat hearts treated with only Isolyte averaged 23.7 +/- 1.7% of the LV muscle area. Intramyocardial injection of HUCBC reduced the infarct size by 71% with 0.5 x 10(6) HUCBC and by 93% with 4 x 10(6) HUCBC in comparison with the controls (p < 0.001). Intracoronary injection reduced the infarction size by 47% with 0.5 x 10(6) HUCBC and by 80% with 4 x 10(6) HUCBC (p < 0.001), and IV HUCBC reduced infarct size by 51% with 0.5 x 10(6) and by 75-77% with 16-32 million HUCBC (p < 0.001) in comparison with control hearts. With 4 x 10(6) HUCBC, infarction size was 65% smaller with IM HUCBC than with IA HUCBC and 78% smaller than with IV HUCBC (p < 0.05). Nevertheless, IM, IA, and IV HUCBC all produced significant reductions in infarct size in comparison with Isolyte-treated infarcted hearts without requirements for host immune suppression. The present experiments demonstrate that the optimal dose

  13. Metastatic Midgut Carcinoid in the Myocardium.

    PubMed

    Bukowczan, Jakub; Lois, Konstantinos B; Skinner, Jane; Petrides, George; James, Robert Andrew; Perros, Petros

    2015-09-01

    Metastasis of neuroendocrine tumor to the myocardium is rare. We present a case of 64-year-old woman, who presented initially with abdominal pain and large adnexal mass. The image-guided biopsy showed low-grade neuroendocrine tumor with Ki67 less than 2% within the ovarian tissue. CT staging revealed bilateral adnexal masses, liver metastases, and primary lesion in the terminal ileum. Octreoscan showed marked tracer uptake within the lower esophagus not related to obvious mass on CT scan; the echocardiography confirmed the presence of a 2.7 cm LV/LA mass. In this case, close correlation between ECHO and the octreoscan obviated need for myocardial biopsy.

  14. Cardiomyopathy development protection after myocardial infarction in rats: Successful competition for major dihydropyridines' common metabolite against captopril.

    PubMed

    Mitręga, Katarzyna A; Spałek, Adrianna M; Nożyński, Jerzy; Porc, Maurycy; Stankiewicz, Magdalena; Krzemiński, Tadeusz F

    2017-01-01

    During the last 25 years angiotensin-converting enzyme inhibitors spectacularly conquered the field of cardiovascular diseases therapy. Nevertheless, lack of new studies concerning side effects associated with their chronic administration seems to be rather confusing. In our previous research, we proved that the main furnidipines' metabolite (M-2) possess multiple cardioprotective actions. Currently, we compared effects of post-infarction long-term oral treatment with M-2 and captopril on hemodynamic parameters and "ischemic cardiomyopathy" development in rats. Myocardial infarction was evoked by permanent left anterior descending coronary artery occlusion for 35 days. Surviving rats were treated with captopril (2 × 25 mg/kg) or M-2 (4 mg/kg) from 6th- 35th day. At 35th day rats' hearts were tested on working heart setup, where following parameters were measured: heart rate, preload pressure, aortic systolic and diastolic pressures, aortic maximum rise and fall, aortic and coronary flow, myocardial oxygen consumption and oximetry in perfusate. Subsequently, heart tissue specimens were assessed during morphological estimation. Captopril caused significant heart rate increase and markedly diminished preload pressure in comparison to M-2. Both drugs evoked essential aortic pressure increase. Aortic flow was significantly decreased after M-2, whereas captopril increased this parameter in comparison to M-2. Both agents caused marked coronary flow increase. Morphologic examination in captopril revealed cardiomyopathic process in 70% of hearts, whereas in M-2 this value reached 30%. Neovascularization of post-infarcted myocardium was visible only after M-2 therapy. Concluding, M-2 presented itself as more attractive agent in long-term post-infarction treatment by preventing cardiomyopathy development, angiogenesis stimulation and preserving cardiac performance.

  15. Prognostic value and determinants of a hypointense infarct core in T2-weighted cardiac magnetic resonance in acute reperfused ST-elevation-myocardial infarction.

    PubMed

    Eitel, Ingo; Kubusch, Konrad; Strohm, Oliver; Desch, Steffen; Mikami, Yoko; de Waha, Suzanne; Gutberlet, Matthias; Schuler, Gerhard; Friedrich, Matthias G; Thiele, Holger

    2011-07-01

    A hypointense core of infarcted myocardium in T2-weighted cardiovascular MRI (CMR) has been used as a noninvasive marker for intramyocardial hemorrhage. However, the clinical significance of such findings not yet been established. The aim of this study was to evaluate determinants and prognostic impact of a hypointense infarct core in T2-weighted CMR images, studied in patients after acute, reperfused ST-elevation-myocardial infarction. We analyzed 346 patients with ST-elevation-myocardial infarction undergoing primary angioplasty < 12 hours after symptoms onset. T2-weighted, contrast-enhanced CMR was used for assessment of the area at risk, myocardial salvage, infarct size, hypointense core in T2-weighted images, and late microvascular obstruction. Patients were categorized into 2 groups defined by the presence or absence of a hypointense core. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and congestive heart failure within 6 months after infarction. A hypointense core was present in 122 (35%) patients and was associated with larger infarcts, greater amount of microvascular obstruction, less myocardial salvage, and impaired left ventricular function (P < 0.001, respectively). The presence of a hypointense core was a strong univariable predictor of major adverse cardiovascular events (hazard ratio, 2.59; confidence interval, 1.27 to 5.27) and was significantly associated with an increased major adverse cardiovascular events rate (16.4% versus 7.0%, P = 0.006) 6 months after infarction. A hypointense infarct core within the area at risk of reperfused infarcted myocardium in T2-weighted CMR is closely related to infarct size, microvascular obstruction, and impaired left ventricular function, with subsequent adverse clinical outcome.

  16. Experimental model of transthoracic, vascular-targeted, photodynamically induced myocardial infarction

    PubMed Central

    Pokreisz, Peter; Schnitzer, Jan E.

    2013-01-01

    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. PMID:24213611

  17. Early post-myocardial infarction survival in MRL mice is mediated by attenuated apoptosis and inflammation but depends on genetic background

    PubMed Central

    Hunt, Darlene L.; Campbell, Patrick H.; Zambon, Alexander C.; Vranizan, Karen; Evans, Sylvia M.; Kuo, Hai-Chien; Yamaguchi, Ken D.; Omens, Jeffrey H.; McCulloch, Andrew D.

    2011-01-01

    The Murphy Roths Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high post-myocardial infarction (MI) survival rate compared with C57BL/6J (C57) mice. The biological processes responsible for this survival advantage are unknown. To assess the effect of genetic background, the LG/J strain, which harbors 75% of the MRL composite genome, was included in the study. The MRL survival advantage versus C57 mice (92% vs. 68%, P < 0.05) occurred primarily in the first 5 days; LG/J survival was intermediate (P = NS). Microarray data analysis revealed an attenuation of apoptotic (P < 0.05) and stress response transcripts in MRL hearts compared with C57 hearts after MI. Supporting the microarray results, there were fewer TUNEL-positive cells 1 day post-MI in MRL infarcts compared with C57 infarcts (P = 0.001) and fewer CD45-positive cells in the MRL infarct border zone 2 days post-MI (P < 0.01). LG/J results were intermediate (P = NS). MRL hearts had smaller infarct scars and attenuated ventricular dilation 30 days post-MI compared with C57 hearts (P < 0.05). We conclude that the early post-MI survival advantage of MRL mice over the C57 strain is mediated at least in part by reductions in apoptosis and inflammatory infiltration, and that these reductions may influence chronic remodeling. The intermediate survival, apoptosis and inflammation profile of LG/J mice suggests this high tolerance for MI in the MRL could be derived from its shared genetic background with the LG/J. PMID:21967898

  18. Early postmyocardial infarction survival in Murphy Roths Large mice is mediated by attenuated apoptosis and inflammation but depends on genetic background.

    PubMed

    Hunt, Darlene L; Campbell, Patrick H; Zambon, Alexander C; Vranizan, Karen; Evans, Sylvia M; Kuo, Hai-Chien; Yamaguchi, Ken D; Omens, Jeffrey H; McCulloch, Andrew D

    2012-01-01

    The Murphy Roths Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high postmyocardial infarction (post-MI) survival rate compared with C57BL/6J (C57) mice. The biological processes responsible for this survival advantage are unknown. To assess the effect of genetic background, the LG/J strain, which harbours 75% of the MRL composite genome, was included in the study. The MRL survival advantage versus C57 mice (92 versus 68%, P < 0.05) occurred primarily in the first 5 days; LG/J survival was intermediate (P = n.s.). Microarray data analysis revealed an attenuation of apoptotic (P < 0.05) and stress response transcripts in MRL hearts compared with C57 hearts post-MI. Supporting the microarray results, there were fewer TUNEL-positive cells 1 day post-MI in MRL infarcts compared with C57 infarcts (P = 0.001) and fewer CD45-positive cells in the MRL infarct border zone 2 days post-MI (P < 0.01); the LG/J results were intermediate (P = n.s.). The MRL hearts had smaller infarct scars and attenuated ventricular dilatation 30 days post-MI compared with C57 hearts (P < 0.05). We conclude that the early post-MI survival advantage of MRL mice over the C57 strain is mediated at least in part by reductions in apoptosis and inflammatory infiltration, and that these reductions may influence chronic remodelling. The intermediate survival, apoptosis and inflammation profile of LG/J mice suggests that this high tolerance for MI in the MRL mouse could be derived from its shared genetic background with the LG/J mouse.

  19. Sinoatrial disease in acute myocardial infarction. Long-term prognosis.

    PubMed Central

    Hatle, L; Bathen, J; Rokseth, R

    1976-01-01

    Of 32 patients with acute myocardial infarction complicated by sinoatrial disease, 23 survived. All 23 had inferior infarction. During follow-up lasting 4 to 6 years only one patient developed severe chronic sinoatrial disease (sick sinus syndrome) necessitating permanent pacemaker treatment; twelve others died during this time. In 2 of them death was sudden 5 and 6 months after infarction. Atrial pacing studies in 7 of the 11 patients still alive showed no gross abnormalities. A review of 71 patients with chronic sinoatrial disease treated with a permanent pacemaker revealed only 5 with previous documented infarction. The present data suggest that sinus node dysfunction in patients surviving acute infarction is most often only temporary as is atrioventricular block. Occasionally, however, severe chronic sinoatrial disease requiring a permanent pacemaker may develop later, and this course of events is most likely to occur in those patients who had additional complications during the acute infarct. PMID:1267985

  20. Injectable shear-thinning hydrogels to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium

    PubMed Central

    Gaffey, Ann C.; Chen, Minna H.; Venkataraman, Chantel M.; Trubelja, Alen; Rodell, Christopher B.; Dinh, Patrick V.; Hung, George; MacArthur, John W.; Soopan, Renganaden V.; Burdick, Jason A.; Atluri, Pavan

    2015-01-01

    OBJECTIVES The clinical translation of cell based therapies for ischemic heart disease has been limited due to low cell retention (<1%) within and poor targeting to ischemic myocardium. To address these issues, we developed an injectable shear-thinning hyaluronic acid hydrogel (STG) and endothelial progenitor cell construct (STG-EPC). The STG assembles due to interactions of adamantine and β-cyclodextrin modified hyaluronic acid. It is shear-thinning to permit delivery via a syringe, and self-heals upon injection within the ischemic myocardium. This directed therapy to the ischemic myocardial borderzone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy. METHODS EPCs (DiLDL+ VEGFR2+ CD34+) were harvested from adult male Wistar Rats, cultured, and then suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. STG-EPC constructs were injected at the borderzone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the eGFP+ EPCs from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (PBS injection), intramyocardial injection of EPCs alone (EPC), injection of the STG alone (STG), and treatment with the gel-EPC construct (STG-EPC). Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis. RESULTS EPCs demonstrated viability within the STG. A marked increase in EPC engraftment was observed one-week post-injection within the treated myocardium with gel delivery when compared to EPC injection alone (17.2 ± 0.8 cells/HPF vs. 3.5 cells ± 1.3 cells/HPF, p = 0.0002). A statistically significant increase in

  1. Infant acute myocarditis mimicking acute myocardial infarction

    PubMed Central

    Tilouche, Samia; Masmoudi, Tasnim; Sahnoun, Maha; Chkirbène, Youssef; Mestiri, Sarra; Boughamoura, Lamia; Ben Dhiab, Mohamed; Souguir, Mohamed Kamel

    2016-01-01

    Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis. PMID:28210569

  2. Early assessment of tissue viability with radioiodinated heptadecanoic acid in reperfused canine myocardium: Comparison with thallium-201

    SciTech Connect

    Chappuis, F.; Meier, B.; Belenger, J.; Blaeuenstein, P.L.; Lerch, R. )

    1990-04-01

    Myocardial scintigraphy with heptadecanoic acid labeled with iodine-123 (123I-HDA) may allow early noninvasive delineation of viable myocardium after reperfusion. In this study myocardial uptake of 123I-HDA was compared with that of thallium-201 in six closed-chest dogs after 5 hours of occlusion followed by 1 hour of reperfusion of the left anterior descending coronary artery. Myocardial blood flow was measured with microspheres, and myocardial viability was assessed by means of triphenyltetrazolium chloride staining. In viable areas of the reperfused region, 123I-HDA uptake, thallium-201 uptake, and myocardial blood flow were similar to those measured in the control circumflex region. However, in infarcted areas they were reduced to 48 +/- 2% (mean +/- SEM; p less than 0.001), 59 +/- 3% (p less than 0.001), and 74 +/- 5% (p less than 0.001) of control values, respectively. Results of multiple regression analysis showed that thallium-201 uptake primarily reflected the level of flow during reperfusion, whereas 123I-HDA uptake was dependent on both myocardial blood flow and viability. At each level of flow, 123I-HDA uptake was significantly lower in infarcted than in viable myocardium. By means of discriminant analysis, 123I-HDA uptake was found to be the single most important predictor of viability, whereas thallium-201 was only of limited importance. Myocardial 123I-HDA uptake greater than or equal to 71% or myocardial thallium-201 uptake greater than or equal to 73% best differentiated viable from infarcted myocardium. According to these criteria, 123I-HDA predicted myocardial viability with a sensitivity of 77%, a specificity of 84% and a predictive accuracy of 81%.

  3. Myofilament dysfunction contributes to impaired myocardial contraction in the infarct border zone.

    PubMed

    Shimkunas, Rafael; Makwana, Om; Spaulding, Kimberly; Bazargan, Mona; Khazalpour, Michael; Takaba, Kiyoaki; Soleimani, Mehrdad; Myagmar, Bat-Erdene; Lovett, David H; Simpson, Paul C; Ratcliffe, Mark B