Revised ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management. Implications for preoperative clinical evaluation.

PubMed

Guarracino, F; Baldassarri, R; Priebe, H J

2015-02-01

Each year, an increasing number of elderly patients with cardiovascular disease undergoing non-cardiac surgery require careful perioperative management to minimize the perioperative risk. Perioperative cardiovascular complications are the strongest predictors of morbidity and mortality after major non-cardiac surgery. A Joint Task Force of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA) has recently published revised Guidelines on the perioperative cardiovascular management of patients scheduled to undergo non-cardiac surgery, which represent the official position of the ESC and ESA on various aspects of perioperative cardiac care. According to the Guidelines effective perioperative cardiac management includes preoperative risk stratification based on preoperative assessment of functional capacity, type of surgery, cardiac risk factors, and cardiovascular function. The ESC/ESA Guidelines discourage indiscriminate routine preoperative cardiac testing, because it is time- and cost-consuming, resource-limiting, and does not improve perioperative outcome. They rather emphasize the importance of individualized preoperative cardiac evaluation and the cooperation between anesthesiologists and cardiologists. We summarize the relevant changes of the 2014 Guidelines as compared to the previous ones, with particular emphasis on preoperative cardiac testing.

Bridging the gap: Hybrid cardiac echo in the critically ill.

PubMed

Glaser, Jacob J; Cardarelli, Cassandra; Galvagno, Samuel; Scalea, Thomas M; Murthi, Sarah B

2016-11-01

Point-of-care ultrasound often includes cardiac ultrasound. It is commonly used to evaluate cardiac function in critically ill patients but lacks the specific quantitative anatomic assessment afforded by standard transthoracic echocardiography (TTE). We developed the Focused Rapid Echocardiographic Examination (FREE), a hybrid between a cardiac ultrasound and TTE that places an emphasis on cardiac function rather than anatomy. We hypothesized that data obtained from FREE correlate well with TTE while providing actionable information for clinical decision making. FREE examinations evaluating cardiac function (left ventricular ejection fraction), diastolic dysfunction (including early mitral Doppler flow [E] and early mitral tissue Doppler [E']), right ventricular function, cardiac output, preload (left ventricular internal dimension end diastole), stroke volume, stroke volume variation, inferior vena cava diameter, and inferior vena cava collapse were performed. Patients who underwent both a TTE and FREE on the same day were identified as the cohort, and quantitative measurements were compared. Correlation analyses were performed to assess levels of agreement. A total of 462 FREE examinations were performed, in which 69 patients had both a FREE and TTE. FREE ejection fraction was strongly correlated with TTE (r = 0.89, 95% confidence interval). Left ventricular outflow tract, left ventricular internal dimension end diastole, E, and lateral E' derived from FREE were also strongly correlated with TTE measurements (r = 0.83, r = 0.94, r = 0.77, and r = 0.88, respectively). In 82% of the patients, right ventricular function for FREE was the same as that reported for TTE; pericardial effusion was detected on both examinations in 94% of the cases. No significant valvular anatomy was missed with the FREE examination. Functionally rather than anatomically based hybrid ultrasound examinations, like the FREE, facilitate decision making for critically ill patients. The FREE's functional assessment correlates well with TTE measurements and may be of significant clinical value in critically ill patients, especially when used in remote operating environments where resources are limited. Diagnostic test, level III.

Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

PubMed Central

Liu, Li; Goldberg, Ira J.

2015-01-01

Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

Functional role of AMP-activated protein kinase in the heart during exercise.

PubMed

Musi, Nicolas; Hirshman, Michael F; Arad, Michael; Xing, Yanqiu; Fujii, Nobuharu; Pomerleau, Jason; Ahmad, Ferhaan; Berul, Charles I; Seidman, Jon G; Tian, Rong; Goodyear, Laurie J

2005-04-11

AMP-activated protein kinase (AMPK) plays a critical role in maintaining energy homeostasis and cardiac function during ischemia in the heart. However, the functional role of AMPK in the heart during exercise is unknown. We examined whether acute exercise increases AMPK activity in mouse hearts and determined the significance of these increases by studying transgenic (TG) mice expressing a cardiac-specific dominant-negative (inactivating) AMPKalpha2 subunit. Exercise increased cardiac AMPKalpha2 activity in the wild type mice but not in TG. We found that inactivation of AMPK did not result in abnormal ATP and glycogen consumption during exercise, cardiac function assessed by heart rhythm telemetry and stress echocardiography, or in maximal exercise capacity.

Time Course of Atrophic Remodeling: Effects of Exercise on Cardiac Morpology and Function

NASA Technical Reports Server (NTRS)

Scott, J. M.; Martin, D.; Caine, T.; Matz, T.; Ploutz-Snyder, L. L.

2014-01-01

Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. Exercise training is one intervention that has been shown to confer favorable improvements in LV mass and function during unloading. However, the format and intensity of exercise required to induce optimal cardiac improvements has not been investigated. PURPOSE: This randomized, controlled trial was designed to 1) comprehensively characterize the time course of unloading-induced morpho-functional remodeling, and 2) examine the effects of high intensity exercise training on cardiac structural and functional parameters during unloading. METHODS: Twenty six subjects completed 70 days of head down tilt bed rest (HDBR): 17 were randomized to exercise training (ExBR) and 9 remained sedentary. Exercise consisted of integrated high intensity, continuous, and resistance exercise. We assessed cardiac morphology (left ventricular mass; LVM) and function (speckle-tracking assessment of longitudinal, radial, and circumferential strain and twist) before (BR-2), during (BR7,21,31,70), and following (BR+0, +3) HDBR. Cardiorespiratory fitness (VO2max) was evaluated before (BR- 3), during (BR4,25,46,68) and following (BR+0) HDBR. RESULTS: Sedentary HDBR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain, and an increase in twist. ExBR mitigated decreases in LVM and function. Change in twist was significantly related to change in VO2max (R=0.68, p<0.01). CONCLUSIONS: Alterations in cardiac morphology and function begin early during unloading. High-intensity exercise attenuates atrophic morphological and functional remodeling.

Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study.

PubMed

Mavinkurve-Groothuis, Annelies M C; Marcus, Karen A; Pourier, Milanthy; Loonen, Jacqueline; Feuth, Ton; Hoogerbrugge, Peter M; de Korte, Chris L; Kapusta, Livia

2013-06-01

The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.

Magnetic resonance-compatible model of isolated working heart from large animal for multimodal assessment of cardiac function, electrophysiology, and metabolism.

PubMed

Vaillant, Fanny; Magat, Julie; Bour, Pierre; Naulin, Jérôme; Benoist, David; Loyer, Virginie; Vieillot, Delphine; Labrousse, Louis; Ritter, Philippe; Bernus, Olivier; Dos Santos, Pierre; Quesson, Bruno

2016-05-15

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications. Copyright © 2016 the American Physiological Society.

Randomised controlled trial of a 12 week yoga intervention on negative affective states, cardiovascular and cognitive function in post-cardiac rehabilitation patients.

PubMed

Yeung, Alan; Kiat, Hosen; Denniss, A Robert; Cheema, Birinder S; Bensoussan, Alan; Machliss, Bianca; Colagiuri, Ben; Chang, Dennis

2014-10-24

Negative affective states such as anxiety, depression and stress are significant risk factors for cardiovascular disease, particularly in cardiac and post-cardiac rehabilitation populations.Yoga is a balanced practice of physical exercise, breathing control and meditation that can reduce psychosocial symptoms as well as improve cardiovascular and cognitive function. It has the potential to positively affect multiple disease pathways and may prove to be a practical adjunct to cardiac rehabilitation in further reducing cardiac risk factors as well as improving self-efficacy and post-cardiac rehabilitation adherence to healthy lifestyle behaviours. This is a parallel arm, multi-centre, randomised controlled trial that will assess the outcomes of post- phase 2 cardiac rehabilitation patients assigned to a yoga intervention in comparison to a no-treatment wait-list control group. Participants randomised to the yoga group will engage in a 12 week yoga program comprising of two group based sessions and one self-administered home session each week. Group based sessions will be led by an experienced yoga instructor. This will involve teaching beginner students a hatha yoga sequence that incorporates asana (poses and postures), pranayama (breathing control) and meditation. The primary outcomes of this study are negative affective states of anxiety, depression and stress assessed using the Depression Anxiety Stress Scale. Secondary outcomes include measures of quality of life, and cardiovascular and cognitive function. The cardiovascular outcomes will include blood pressure, heart rate, heart rate variability, pulse wave velocity, carotid intima media thickness measurements, lipid/glucose profiles and C-reactive protein assays. Assessments will be conducted prior to (week 0), mid-way through (week 6) and following the intervention period (week 12) as well as at a four week follow-up (week 16). This study will determine the effect of yoga practice on negative affective states, cardiovascular and cognitive function in post-phase 2 cardiac rehabilitation patients. The findings may provide evidence to incorporate yoga into standardised cardiac rehabilitation programs as a practical adjunct to improve the management of psychosocial symptoms associated with cardiovascular events in addition to improving patients' cognitive and cardiovascular functions. ACTRN12612000358842.

Feature tracking cardiac magnetic resonance imaging: A review of a novel non-invasive cardiac imaging technique

PubMed Central

Rahman, Zia Ur; Sethi, Pooja; Murtaza, Ghulam; Virk, Hafeez Ul Hassan; Rai, Aitzaz; Mahmod, Masliza; Schoondyke, Jeffrey; Albalbissi, Kais

2017-01-01

Cardiovascular disease is a leading cause of morbidity and mortality globally. Early diagnostic markers are gaining popularity for better patient care disease outcomes. There is an increasing interest in noninvasive cardiac imaging biomarkers to diagnose subclinical cardiac disease. Feature tracking cardiac magnetic resonance imaging is a novel post-processing technique that is increasingly being employed to assess global and regional myocardial function. This technique has numerous applications in structural and functional diagnostics. It has been validated in multiple studies, although there is still a long way to go for it to become routine standard of care. PMID:28515849

Inhibition of Oct 3/4 mitigates the cardiac progenitor-derived myocardial repair in infarcted myocardium.

PubMed

Zhao, Yu Tina; Du, Jianfeng; Chen, Youfang; Tang, Yaoliang; Qin, Gangjian; Lv, Guorong; Zhuang, Shougang; Zhao, Ting C

2015-12-24

Recent evidence has demonstrated that cardiac progenitor cells play an essential role in the induction of angiomyogenesis in infarcted myocardium. We and others have shown that engraftment of c-kit(+) cardiac stem cells (CSCs) into infarcted hearts led to myocardium regeneration and neovascularization, which was associated with an improvement of ventricular function. The purpose of this study is aimed at investigating the functional role of transcription factor (TF) Oct3/4 in facilitating CSCs to promote myocardium regeneration and preserve cardiac performance in the post-MI heart. c-kit(+) CSCs were isolated from adult hearts and re-introduced into the infarcted myocardium in which the mouse MI model was created by permanent ligation of the left anterior descending artery (LAD). The Oct3/4 of CSCs was inhibited by transfection of Oct3/4 siRNA, and transfection of CSCs with control siRNA serves as control groups. Myocardial functions were evaluated by echocardiographic measurement. Histological analysis was employed to assess newly formed cardiogenesis, neovascularization, and cell proliferations. Terminal deoxynucleotidyltransferase (TdT) nick-end labeling (TUNEL) was carried out to assess apoptotic cardiomyocytes. Real time polymerase chain reaction and Western blot were carried out to evaluate the level of Oct 3/4 in CSCs. Two weeks after engraftment, CSCs increased ventricular functional recovery as shown by a serial echocardiographic measurement, which is concomitant with the suppression of cardiac hypertrophy and attenuation of myocardial interstitial fibrosis. Suppression of Oct 3/4 of CSCs abrogated functional improvements and mitigated the hypertrophic response and cardiac remodeling. Transplantation of c-kit(+) CSCs into MI hearts promoted cardiac regeneration and neovascularization, which were abolished with the knockdown of Oct3/4. Additionally, suppression of Oct3/4 abrogated myocyte proliferation in the CSC-engrafted myocardium. Our results indicate that CSCs-derived cardiac regeneration improves the restoration of cardiac function and is mediated through Oct 3/4.

Combining wet and dry research: experience with model development for cardiac mechano-electric structure-function studies

PubMed Central

Quinn, T. Alexander; Kohl, Peter

2013-01-01

Since the development of the first mathematical cardiac cell model 50 years ago, computational modelling has become an increasingly powerful tool for the analysis of data and for the integration of information related to complex cardiac behaviour. Current models build on decades of iteration between experiment and theory, representing a collective understanding of cardiac function. All models, whether computational, experimental, or conceptual, are simplified representations of reality and, like tools in a toolbox, suitable for specific applications. Their range of applicability can be explored (and expanded) by iterative combination of ‘wet’ and ‘dry’ investigation, where experimental or clinical data are used to first build and then validate computational models (allowing integration of previous findings, quantitative assessment of conceptual models, and projection across relevant spatial and temporal scales), while computational simulations are utilized for plausibility assessment, hypotheses-generation, and prediction (thereby defining further experimental research targets). When implemented effectively, this combined wet/dry research approach can support the development of a more complete and cohesive understanding of integrated biological function. This review illustrates the utility of such an approach, based on recent examples of multi-scale studies of cardiac structure and mechano-electric function. PMID:23334215

Higher protein intake increases cardiac function parameters in healthy children: metabolic programming by infant nutrition-secondary analysis from a clinical trial.

PubMed

Collell, Rosa; Closa-Monasterolo, Ricardo; Ferré, Natalia; Luque, Veronica; Koletzko, Berthold; Grote, Veit; Janas, Roman; Verduci, Elvira; Escribano, Joaquín

2016-06-01

Protein intake may modulate cardiac structure and function in pathological conditions, but there is a lack of knowledge on potential effects in healthy infants. Secondary analysis of an ongoing randomized clinical trial comparing two groups of infants receiving a higher (HP) or lower (LP) protein content formula in the first year of life, and compared with an observational group of breastfed (BF) infants. Growth and dietary intake were assessed periodically from birth to 2 y. Insulin-like growth factor 1 (IGF-1) axis parameters were analyzed at 6 mo in a blood sample. At 2 y, cardiac mass and function were assessed by echocardiography. HP infants (n = 50) showed a higher BMI z-score at 2 y compared with LP (n = 47) or BF (n = 44). Cardiac function parameters were increased in the HP group compared with the LP and were directly related to the protein intake during the first 6 mo of life. Moreover, there was an increase in free IGF-1 in the HP group at 6 mo. A moderate increase in protein supply during the first year of life is associated with higher cardiac function parameters at 2 y. IGF-1 axis modifications may, at least in part, underlie these effects.

Cardiac function, myocardial mechano-energetic efficiency, and ventricular-arterial coupling in normal pregnancy.

PubMed

Iacobaeus, Charlotte; Andolf, Ellika; Thorsell, Malin; Bremme, Katarina; Östlund, Eva; Kahan, Thomas

2018-04-01

To assess cardiac function, myocardial mechanoenergetic efficiency (MEE), and ventricular-arterial coupling (VAC) longitudinally during normal pregnancy, and to study if there was an association between cardiac structure and function, and fetal growth. Cardiac structure and function, MEE, and ventricular-arterial coupling was assessed longitudinally in 52 healthy nulliparous women at 14, 24, and 34 weeks' gestation and 9-month postpartum. Left atrial diameter increased during pregnancy (30.41 ± 3.59 mm in the nonpregnant state and 31.02 ± 3.91, 34.06 ± 3.58, and 33.9 ± 2.97 mm in the first, second, and third trimesters, P < 0.001). Left ventricular mass increased 117.12 ± 45.0 g in the nonpregnant state and 116.5 ± 33.0, 126.9 ± 34.5, 128.4 ± 36 g in the first, second, and third trimesters (P < 0.001). Cardiac output increased from 3.4 ± 1.2 l/min to 4.3 ± 0.7 l/min in the second and third trimesters (P < 0.001). Diastolic function decreased as both E/A and e'/a' decreased during pregnancy (P < 0.05 and P < 0.001, respectively). MEE and VAC were retained during pregnancy. Heart rate was associated with birth weight centile in the first (r = 0.41, P = 0.002) and second (r = 0.46, P = 0.002) trimester. The increase in cardiac output during normal pregnancy is obtained by an increase in heart rate, followed by structural cardiac changes. The impaired systolic function is accomplished by a deteriorated diastolic function. Despite these rapid changes, the myocardium manages to work efficient with a preserved MEE. Cardiac and arterial adaption to pregnancy seems to appear parallel as evidenced by a preserved VAC.

Chronic losartan administration reduces mortality and preserves cardiac but not skeletal muscle function in dystrophic mice.

PubMed

Bish, Lawrence T; Yarchoan, Mark; Sleeper, Meg M; Gazzara, Jeffrey A; Morine, Kevin J; Acosta, Pedro; Barton, Elisabeth R; Sweeney, H Lee

2011-01-01

Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6-9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the study endpoint, 88% of treated mice were alive compared to only 44% of untreated (p = 0.05). No difference in skeletal muscle morphology, function, or fibrosis was noted in losartan-treated animals. Cardiac function was significantly preserved with losartan treatment, with a trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal muscle disease progression, suggesting that other pathways that trigger fibrosis dominate over angiotensin II in skeletal muscle long term, unlike the situation in the heart. Our study suggests that ARB may be an important prophylactic treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle disease.

Defining the Process of a Cardiovascular Risk Assessment Program: Lessons Learnt From Cardiac Assessment of Elite Soccer Players in the United Kingdom.

PubMed

Speers, Christopher; Seth, Ajai Narain; Patel, Kiran Chhaganbhai; Rakhit, Dhrubo Jyoti; Gillett, Mark James

2017-12-14

Retrospectively analyze the cardiac assessment process for elite soccer players, and provide team physicians with a systematic guide to managing longitudinal cardiac risk. Descriptive Epidemiology Study. Cardiac assessments incorporating clinical examination, 12-lead ECG, echocardiography, and health questionnaire. Soccer players at 5 professional clubs in England, the United Kingdom. Data was retrospectively collected, inspected, and analyzed to determine their clinical management and subsequent follow-up. Over 2 years, 265 soccer players, aged 13 to 37 years with 66% of white European ethnicity, were included in the cohort. Eleven percent had "not-normal" assessments, of these assessments, 83% were considered gray screens, falling into three broad categories: structural cardiac features (including valvular abnormalities), functional cardiac features, and electrocardiogram changes. After cardiology consultation, all assessments were grouped into low, enhanced and high-risk categories for ongoing longitudinal risk management. Overall clear-cut pathology was identified in 2%. Cardiovascular assessment is a vital tool in identifying athletes at risk of sudden cardiac death to mitigate their risk through surveillance, intervention, or participation restriction. The decision whether a player is fit to play or not requires a robust risk assessment followed by input from a multidisciplinary team that includes both the team physician and cardiologist. This educational article proposes a clinical management pathway to aid clinicians with this process. Sudden cardiac death is the important medical cause of death during exercise. The team physician should assume responsibility for the management of the longitudinal risk of their players' cardiac assessments in conjunction with sports cardiologist.

Performance of Automated Software in the Assessment of Segmental Left Ventricular Function in Cardiac CT: Comparison with Cardiac Magnetic Resonance.

PubMed

Wang, Rui; Meinel, Felix G; Schoepf, U Joseph; Canstein, Christian; Spearman, James V; De Cecco, Carlo N

2015-12-01

To evaluate the accuracy, reliability and time saving potential of a novel cardiac CT (CCT)-based, automated software for the assessment of segmental left ventricular function compared to visual and manual quantitative assessment of CCT and cardiac magnetic resonance (CMR). Forty-seven patients with suspected or known coronary artery disease (CAD) were enrolled in the study. Wall thickening was calculated. Segmental LV wall motion was automatically calculated and shown as a colour-coded polar map. Processing time for each method was recorded. Mean wall thickness in both systolic and diastolic phases on polar map, CCT, and CMR was 9.2 ± 0.1 mm and 14.9 ± 0.2 mm, 8.9 ± 0.1 mm and 14.5 ± 0.1 mm, 8.3 ± 0.1 mm and 13.6 ± 0.1 mm, respectively. Mean wall thickening was 68.4 ± 1.5 %, 64.8 ± 1.4 % and 67.1 ± 1.4 %, respectively. Agreement for the assessment of LV wall motion between CCT, CMR and polar maps was good. Bland-Altman plots and ICC indicated good agreement between CCT, CMR and automated polar maps of the diastolic and systolic segmental wall thickness and thickening. The processing time using polar map was significantly decreased compared with CCT and CMR. Automated evaluation of segmental LV function with polar maps provides similar measurements to manual CCT and CMR evaluation, albeit with substantially reduced analysis time. • Cardiac computed tomography (CCT) can accurately assess segmental left ventricular wall function. • A novel automated software permits accurate and fast evaluation of wall function. • The software may improve the clinical implementation of segmental functional analysis.

Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

PubMed

Liang, Zhongshu; Leo, Sunnar; Wen, Helin; Ouyang, Mao; Jiang, Weihong; Yang, Kan

2015-05-13

Triptolide treatment leads to an improvement in Diabetic Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is characterized by abnormal cardiac energy metabolism. We hypothesized that triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac energy metabolism in vivo and evaluating the effect of triptolide treatment in DCM rats. Six weeks triptolide treatment was conducted on streptozotocin-induced diabetic rats with dose of 100, 200 or 400 μg/kg/day respectively. Sex- and age-matched non-diabetic rats were used as control group. Cardiac chamber dimension and function were determined with echocardiography. Whole heart preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured using real time PCR and western blot analysis. In diabetic rats, cardiac mass index was significantly higher, where as cardiac EF was lower than control group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic groups were also remarkably lower than control group. Compared to non-treated diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best improvement was seen in group treated with Triptolide with dose 200 μg/kg/day. (31)P NMR spectroscopy enables assessment of cardiac energy metabolism in whole heart preparations. It detects energy metabolic abnormalities in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac energy metabolism at least partly through upregulation of MAPK signaling transduction.

Functional Cardiac Magnetic Resonance Imaging (MRI) in the Assessment of Myocardial Viability and Perfusion

PubMed Central

2003-01-01

Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness safety and cost-effectiveness of using functional cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability and perfusion in patients with coronary artery disease and left ventricular dysfunction. Results Functional MRI has become increasingly investigated as a noninvasive method for assessing myocardial viability and perfusion. Most patients in the published literature have mild to moderate impaired LV function. It is possible that the severity of LV dysfunction may be an important factor that can alter the diagnostic accuracy of imaging techniques. There is some evidence of comparable or better performance of functional cardiac MRI for the assessment of myocardial viability and perfusion compared with other imaging techniques. However limitations to most of the studies included: Functional cardiac MRI studies that assess myocardial viability and perfusion have had small sample sizes. Some studies assessed myocardial viability/perfusion in patients who had already undergone revascularization, or excluded patients with a prior MI (Schwitter et al., 2001). Lack of explicit detail of patient recruitment. Patients with LVEF >35%. Interstudy variability in post MI imaging time(including acute or chronic MI), when patients with a prior MI were included. Poor interobserver agreement (kappa statistic) in the interpretation of the results. Traditionally, 0.80 is considered “good”. Cardiac MRI measurement of myocardial perfusion to as an adjunct tool to help diagnose CAD (prior to a definitive coronary angiography) has also been examined in some studies, with methodological limitations, yielding comparable results. Many studies examining myocardial viability and perfusion report on the accuracy of imaging methods with limited data on long-term patient outcome and management. Kim et al. (2000) revealed that the transmural extent of hyperenhancement was significantly related to the likelihood of improvement in contractility after revascularization. However, the LVEF in the patient population was 43% prior to revascularization. It is important to know whether the technique has the same degree of accuracy in patients who have more severe LV dysfunction and who would most benefit from an assessment of myocardial viability. “Substantial” viability used as a measure of a patient’s ability to recover after revascularization has not been definitively reported (how much viability is enough?). Patients with severe LV dysfunction are more likely to have mixtures of surviving myocardium, including normal, infarcted, stunned and hibernating myocardium (Cowley et al., 1999). This may lead to a lack of homogeneity of response to testing and to revascularization and contribute to inter- and intra-study differences. There is a need for a large prospective study with adequate follow-up time for patients with CAD and LV dysfunction (LVEF<35%) comparing MRI and an alternate imaging technique. There is some evidence that MRI has comparable sensitivity, specificity and accuracy to PET for determining myocardial viability. However, there is a lack of evidence comparing the accuracy of these two techniques to predict LV function recovery. In addition, some studies refer to PET as the gold standard for the assessment of myocardial viability. Therefore, PET may be an ideal noninvasive imaging comparator to MRI for a prospective study with follow-up. To date, there is a lack of cost-effectiveness analyses (or any economic analyses) of functional cardiac MRI versus an alternate noninvasive imaging method for the assessment of myocardial viability/perfusion. Conclusion There is some evidence that the accuracy of functional cardiac MRI compares favourably with alternate imaging techniques for the assessment of myocardial viability and perfusion. There is insufficient evidence whether functional cardiac MRI can better select which patients [who have CAD and severe LV dysfunction (LVEF <35%)] may benefit from revascularization compared with an alternate noninvasive imaging technology. There is insufficient evidence whether functional cardiac MRI can better select which patients should proceed to invasive coronary angiography for the definitive diagnosis of CAD, compared with an alternate noninvasive imaging technology. There is a need for a large prospective (potentially multicentre) study with adequate follow-up time for patients with CAD and LV dysfunction (LVEF<35%) comparing MRI and PET. Since longer follow-up time may be associated with restenosis or graft occlusion, it has been suggested to have serial measurements after revascularization (Cowley et al., 1999). PMID:23074446

Cardiac nuclear medicine, part II: diagnosis of coronary artery diseas

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

Polak, J.F.; Holman, B.L.

Diagnosing coronary artery disease is difficult and requires careful consideration of the roles and limitations of the tests used. Standard ECG tests are not reliable indicators of the presence of disease in asymptomatic patients. Thallium stress testing to assess ischemia and exercise ventriculography to assess functional status of the heart are limited in sensitivity and specificity. This is the second of a three-part series on cardiac nuclear medicine. Part I (Med. Instrum., May-June, 1981) focused on the commonly used examinations in cardiac physiology and pathophysiology. Part III will focus on myocardial infarction and other cardiac diseases.

Positron Emission Tomography of the Heart

DOE R&D Accomplishments Database

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

1979-01-01

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

Standardization of the two-dimensional transcoelomic echocardiographic examination in the central bearded dragon (Pogona vitticeps).

PubMed

Silverman, S; Sanchez-Migallon Guzman, D; Stern, J; Gustavsen, K A; Griffiths, L G

2016-06-01

To objectively and subjectively describe the normal spectrum of two-dimensional echocardiographic findings in the central bearded dragon (Pogona vitticeps). Sixteen central bearded dragons. Central bearded dragons were prospectively evaluated under manual restraint in right and left lateral recumbency to identify imaging planes for reproducible measurements of cardiac chambers, subjective two-dimensional analysis and color Doppler assessment. Echocardiography can be performed through windows in the left and right axillae. The window in the left axilla allows for a subjective and objective assessment of cardiac structure and function. The right axillary window allows for evaluation of pulmonary artery flow. Both views provide data for the presence of pericardial effusion or valvular insufficiency. With optimized imaging planes, cardiac chambers and fractional area change along with fractional shortening in the longitudinal and transverse planes can be calculated. Body weight and cardiac chamber dimensions of males were significantly larger than females. Ventricular fractional area change was the most consistent functional assessment. The majority of animals were found to have no evidence of valvular insufficiency, while approximately half had evidence of pericardial fluid. Pulmonary artery flow was assessed in all patients. Left and right aortic velocities cannot be reliably obtained. This study is the first to generate reference values for cardiac structure and function in clinically healthy central bearded dragons. Valvular insufficiency is not a normal finding in central bearded dragons, while mild pericardial effusion may be. Copyright © 2015 Elsevier B.V. All rights reserved.

A home-based exercise program for children with congenital heart disease following interventional cardiac catheterization: study protocol for a randomized controlled trial.

PubMed

Du, Qing; Salem, Yasser; Liu, Hao Howe; Zhou, Xuan; Chen, Sun; Chen, Nan; Yang, Xiaoyan; Liang, Juping; Sun, Kun

2017-01-23

Cardiac catheterization has opened an innovative treatment field for cardiac disease; this treatment is becoming the most popular approach for pediatric congenital heart disease (CHD) and has led to a significant growth in the number of children with cardiac catheterization. Unfortunately, based on evidence, it has been demonstrated that the majority of children with CHD are at an increased risk of "non-cardiac" problems. Effective exercise therapy could improve their functional status significantly. As studies identifying the efficacy of exercise therapy are rare in this field, the aims of this study are to (1) identify the efficacy of a home-based exercise program to improve the motor function of children with CHD with cardiac catheterization, (2) reduce parental anxiety and parenting burden, and (3) improve the quality of life for parents whose children are diagnosed with CHD with cardiac catheterization through the program. A total of 300 children who will perform a cardiac catheterization will be randomly assigned to two groups: a home-based intervention group and a control group. The home-based intervention group will carry out a home-based exercise program, and the control group will receive only home-based exercise education. Assessments will be undertaken before catheterization and at 1, 3, and 6 months after catheterization. Motor ability quotients will be assessed as the primary outcomes. The modified Ross score, cardiac function, speed of sound at the tibia, functional independence of the children, anxiety, quality of life, and caregiver burden of their parents or the main caregivers will be the secondary outcome measurements. The proposed prospective randomized controlled trial will evaluate the efficiency of a home-based exercise program for children with CHD with cardiac catheterization. We anticipate that the home-based exercise program may represent a valuable and efficient intervention for children with CHD and their families. http://www.chictr.org.cn/ on: ChiCTR-IOR-16007762 . Registered on 13 January 2016.

The Correlation of Skeletal and Cardiac Muscle Dysfunction in Duchenne Muscular Dystrophy.

PubMed

Posner, Andrew D; Soslow, Jonathan H; Burnette, W Bryan; Bian, Aihua; Shintani, Ayumi; Sawyer, Douglas B; Markham, Larry W

2016-01-01

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle and cardiac dysfunction. While skeletal muscle dysfunction precedes cardiomyopathy, the relationship between the progressive decline in skeletal and cardiac muscle function is unclear. This relationship is especially important given that the myocardial effects of many developing DMD therapies are largely unknown. Our objective was to assess the relationship between progression of skeletal muscle weakness and onset of cardiac dysfunction in DMD. A total of 77 DMD subjects treated at a single referral center were included. Demographic information, quantitative muscle testing (QMT), subjective muscle strength, cardiac function, and current and retrospective medications were collected. A Spearman rank correlation was used to evaluate for an association between subjective strength and fractional shortening. The effects of total QMT and arm QMT on fractional shortening were examined in generalized least square with and without adjustments for age, ambulatory status, and duration of corticosteroids and cardiac specific medications. We found a significant correlation between maintained subjective skeletal muscle arm and leg strength and maintained cardiac function as defined by fractional shortening (rho=0.47, p=0.004 and rho=0.48, p=0.003, respectively). We also found a significant association between QMT and fractional shortening among non-ambulatory DMD subjects (p=0.03), while this association was not significant in ambulatory subjects. Our findings allow us to conclude that in this population, there exists a significant relationship between skeletal muscle and cardiac function in non-ambulatory DMD patients. While this does not imply a causal relationship, a possible association between skeletal and cardiac muscle function suggests that researchers should carefully monitor cardiac function, even when the primary outcome measures are not cardiac in nature.

Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

NASA Astrophysics Data System (ADS)

Rogozhnikov, Dmitry; O'Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.

2016-12-01

There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

Intermedin improves cardiac function and sympathetic neural remodeling in a rat model of post myocardial infarction heart failure

PubMed Central

Xu, Bin; Xu, Hao; Cao, Heng; Liu, Xiaoxiao; Qin, Chunhuan; Zhao, Yanzhou; Han, Xiaolin; Li, Hongli

2017-01-01

Emerging evidence has suggested that intermedin (IMD), a novel member of the calcitonin gene-related peptide (CGRP) family, has a wide range of cardioprotective effects. The present study investigated the effects of long-term administration of IMD on cardiac function and sympathetic neural remodeling in heart failure (HF) rats, and studied potential underlying mechanism. HF was induced in rats by myocardial infarction (MI). Male Sprague Dawley rats were randomly assigned to either saline or IMD (0.6 µg/kg/h) treatment groups for 4 weeks post-MI. Another group of sham-operated rats served as controls. Cardiac function was assessed by echocardiography, cardiac catheterization and plasma level of B-type natriuretic peptide (BNP). Cardiac sympathetic neural remodeling was assessed by immunohistochemistical study of tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) immunoreactive nerve fibers. The protein expression levels of nerve growth factor (NGF), TH and GAP43 in the ventricular myocardium were studied by western blotting. Ventricular fibrillation threshold (VFT) was determined to evaluate the incidence of ventricular arrhythmia. Oxidative stress was assessed by detecting the activity of superoxide dismutase and the level of malondialdehyde. Compared with rats administrated with saline, IMD significantly improved cardiac function, decreased the plasma BNP level, attenuated sympathetic neural remodeling, increased VFT and suppressed oxidative stress. In conclusion, these results indicated that IMD prevents ventricle remodeling and improves the performance of a failing heart. In addition, IMD attenuated sympathetic neural remodeling and reduced the incidence of ventricular arrhythmia, which may contribute to its anti-oxidative property. These results implicate IMD as a potential therapeutic agent for the treatment of HF. PMID:28627670

Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus.

PubMed

Tong, Jing; Lai, Yan; Yao, Yi-An; Wang, Xue-Jun; Shi, Yu-Shuang; Hou, Han-Jin; Gu, Jian-Yun; Chen, Fei; Liu, Xue-Bo

2018-06-19

To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice. © 2018 The Author(s). Published by S. Karger AG, Basel.

Relation between the Disability of the Arm, Shoulder and Hand Score and Muscle Strength in Post-Cardiac Surgery Patients.

PubMed

Izawa, Kazuhiro P; Kasahara, Yusuke; Hiraki, Koji; Hirano, Yasuyuki; Watanabe, Satoshi

2017-11-27

Background: The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire is a valid and reliable patient-reported outcome measure. DASH can be assessed by self-reported upper extremity disability and symptoms. We aimed to examine the relationship between the physiological outcome of muscle strength and the DASH score after cardiac surgery. Methods: This cross-sectional study assessed 50 consecutive cardiac patients that were undergoing cardiac surgery. Physiological outcomes of handgrip strength and knee extensor muscle strength and the DASH score were measured at one month after cardiac surgery and were assessed. Results were analyzed using Spearman correlation coefficients. Results: The final analysis comprised 43 patients (men: 32, women: 11; age: 62.1 ± 9.1 years; body mass index: 22.1 ± 4.7 kg/m²; left ventricular ejection fraction: 53.5 ± 13.7%). Respective handgrip strength, knee extensor muscle strength, and DASH score were 27.4 ± 8.3 kgf, 1.6 ± 0.4 Nm/kg, and 13.3 ± 12.3, respectively. The DASH score correlated negatively with handgrip strength ( r = -0.38, p = 0.01) and with knee extensor muscle strength ( r = -0.32, p = 0.04). Conclusion: Physiological outcomes of both handgrip strength and knee extensor muscle strength correlated negatively with the DASH score. The DASH score appears to be a valuable tool with which to assess cardiac patients with poor physiological outcomes, particularly handgrip strength as a measure of upper extremity function, which is probably easier to follow over time than lower extremity function after patients complete cardiac rehabilitation.

Physical activity and cardiac function in the oldest old.

PubMed

Stessman-Lande, Irit; Jacobs, Jeremy M; Gilon, Dan; Leibowitz, David

2012-02-01

The relationship of physical activity (PA) and cardiac function in the oldest old remains unclear. The objective of this study was to evaluate the relationship between PA and cardiac structure and function, in the oldest old. Subjects were recruited from the Jerusalem Longitudinal Cohort Study that was initiated in 1990 and has followed an age homogeneous cohort of Jerusalem residents born in 1920-1921. A total of 496 of the subjects from the most recent set of data collection in 2005-2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. Standard echocardiographic assessment of cardiac structure and function including ejection fraction (EF) and diastolic function as assessed by E:E' measurements was performed. PA was defined as a dichotomous (≥4 hr of light exercise weekly) and as a categorical variable (<4 hr weekly/4 hours weekly/at least 1 hr daily/sport at least twice weekly). On bivariate analysis, mean EF was lower among sedentary versus active women (55.5%±8.5% vs. 58.4%±8.3, p=0.021). No other significant differences were observed between sedentary and active subjects, for either systolic or diastolic function. After adjusting for sex, education, diabetes, ischemic heart disease, hypertension, dependence in activities of daily living, and body mass index (BMI), no significant associations were found between systolic or diastolic function, or left ventricular structure and PA. Gender-specific analyses yielded similar findings. Our study of the oldest old did not demonstrate an association between PA and cardiac structure or function.

Latent cardiac dysfunction as assessed by echocardiography in bed-bound patients following cerebrovascular accidents: comparison with nutritional status.

PubMed

Masugata, Hisashi; Senda, Shoichi; Goda, Fuminori; Yoshihara, Yumiko; Yoshikawa, Kay; Fujita, Norihiro; Himoto, Takashi; Okuyama, Hiroyuki; Taoka, Teruhisa; Imai, Masanobu; Kohno, Masakazu

2007-07-01

The aim of this study was to elucidate the cardiac function in bed-bound patients following cerebrovascular accidents. In accord with the criteria for activities of daily living (ADL) of the Japanese Ministry of Health, Labour and Welfare, 51 age-matched poststroke patients without heart disease were classified into 3 groups: rank A (house-bound) (n = 16, age, 85 +/- 6 years), rank B (chair-bound) (n = 16, age, 84 +/- 8 years), and rank C (bed-bound) (n = 19, age, 85 +/- 9 years). Using echocardiography, the left ventricular (LV) diastolic function was assessed by the ratio of early filling (E) and atrial contraction (A) transmitral flow velocities (E/A) of LV inflow. LV systolic function was assessed by LV ejection fraction (LVEF), and the Tei index was also measured to assess both LV systolic and diastolic function. No difference was observed in the E/A and LVEF among the 3 groups. The Tei index was higher in rank C (0.56 +/- 0.17) than in rank A (0.39 +/- 0.06) and rank B (0.48 +/- 0.17), and a statistically significant difference was observed between rank A and rank C (P < 0.05). Serum albumin and blood hemoglobin were significantly lower in rank C (3.1 +/- 0.4 and 10.6 +/- 1.8 g/dL) than in rank A (4.1 +/- 0.3 and 12.4 +/- 1.2 g/dL) (P < 0.001 and P < 0.05, respectively). These results indicate that latent cardiac dysfunction and poor nutritional status may exist in bed-bound patients (rank C) following cerebrovascular accidents. The Tei index may be a useful index of cardiac dysfunction in bed-bound patients because it is independent of the cardiac loading condition.

Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats.

PubMed

Wang, Jun; Wu, Yajing; Yuan, Fang; Liu, Yixian; Wang, Xuefeng; Cao, Feng; Zhang, Yi; Wang, Sheng

2016-09-01

Radiation-induced heart damage (RIHD) is becoming an increasing concern for patients and clinicians due to the use of radiotherapy for thoracic tumor. Chronic intermittent hypobaric hypoxia (CIHH) preconditioning has been documented to exert a cardioprotective effect. Here we hypothesized that CIHH was capable of attenuating functional and structural damage in a rat model of RIHD. Male adult Sprague-Dawley rats were randomly divided into 4 groups: control, radiation, CIHH and CIHH plus radiation. Cardiac function was measured using Langendorff perfusion in in vitro rat hearts. Cardiac fibrosis, oxidative stress and endoplasmic reticulum stress (ERS) was assessed by quantitative analysis of protein expression. No significant difference between any two groups was observed in baseline cardiac function as assessed by left ventricular end diastolic pressure (LVEDP), left ventricular developing pressure (LVDP) and the derivative of left ventricular pressure (±LVdp/dt). When challenged by ischemia/reperfusion, LVEDP was increased but LVDP and ±LVdp/dt was decreased significantly in radiation group compared with controls, accompanied by an enlarged infarct size and decreased coronary flow. Importantly, CIHH dramatically improved radiation-induced damage of cardiac function and blunted radiation-induced cardiac fibrosis in the perivascular and interstitial area. Furthermore, CIHH abrogated radiation-induced increase in malondialdehyde and enhanced total superoxide dismutase activity, as well as downregulated expression levels of ERS markers like GRP78 and CHOP. CIHH pretreatment alleviated radiation-induced damage of cardiac function and fibrosis. Such a protective effect was closely associated with suppression of oxidative stress and ERS responses. Copyright © 2016 Elsevier Inc. All rights reserved.

A patient self-assessment tool for cardiac rehabilitation.

PubMed

Phelan, C; Finnell, M D; Mottla, K A

1989-01-01

A patient self-assessment tool was designed, tested, and implemented to promote cardiac-specific data collection, based on Gordon's Functional Health Patterns, to maximize patient/family involvement in determining a plan of care, and to streamline primary nurses' documentation requirements. Retrospective and concurrent chart reviews provided data for quality assurance monitoring. The results of the monitoring demonstrated that the self-assessment tool markedly improved the patient-specific data base.

3D cardiac wall thickening assessment for acute myocardial infarction

NASA Astrophysics Data System (ADS)

Khalid, A.; Chan, B. T.; Lim, E.; Liew, Y. M.

2017-06-01

Acute myocardial infarction (AMI) is the most severe form of coronary artery disease leading to localized myocardial injury and therefore irregularities in the cardiac wall contractility. Studies have found very limited differences in global indices (such as ejection fraction, myocardial mass and volume) between healthy subjects and AMI patients, and therefore suggested regional assessment. Regional index, specifically cardiac wall thickness (WT) and thickening is closely related to cardiac function and could reveal regional abnormality due to AMI. In this study, we developed a 3D wall thickening assessment method to identify regional wall contractility dysfunction due to localized myocardial injury from infarction. Wall thickness and thickening were assessed from 3D personalized cardiac models reconstructed from cine MRI images by fitting inscribed sphere between endocardial and epicardial wall. The thickening analysis was performed in 5 patients and 3 healthy subjects and the results were compared against the gold standard 2D late-gadolinium-enhanced (LGE) images for infarct localization. The notable finding of this study is the highly accurate estimation and visual representation of the infarct size and location in 3D. This study provides clinicians with an intuitive way to visually and qualitatively assess regional cardiac wall dysfunction due to infarction in AMI patients.

Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity.

PubMed

Broussard, Josiane L; Nelson, Michael D; Kolka, Cathryn M; Bediako, Isaac Asare; Paszkiewicz, Rebecca L; Smith, Laura; Szczepaniak, Edward W; Stefanovski, Darko; Szczepaniak, Lidia S; Bergman, Richard N

2016-01-01

The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine-16 without affecting calcium handling.

PubMed

Lima-Leopoldo, Ana Paula; Leopoldo, André S; da Silva, Danielle C T; do Nascimento, André F; de Campos, Dijon H S; Luvizotto, Renata A M; de Deus, Adriana F; Freire, Paula P; Medeiros, Alessandra; Okoshi, Katashi; Cicogna, Antonio C

2014-09-15

Few studies have evaluated the relationship between the duration of obesity, cardiac function, and the proteins involved in myocardial calcium (Ca(2+)) handling. We hypothesized that long-term obesity promotes cardiac dysfunction due to a reduction of expression and/or phosphorylation of myocardial Ca(2+)-handling proteins. Thirty-day-old male Wistar rats were distributed into two groups (n = 10 each): control (C; standard diet) and obese (Ob; high-fat diet) for 30 wk. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle. Cardiac protein expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), calsequestrin, L-type Ca(2+) channel, and phospholamban (PLB), as well as PLB serine-16 phosphorylation (pPLB Ser(16)) and PLB threonine-17 phosphorylation (pPLB Thr(17)) were determined by Western blot. The adiposity index was higher (82%) in Ob rats than in C rats. Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C. The Ob muscles developed similar baseline data and myocardial responsiveness to increased extracellular Ca(2+). Obesity caused a reduction in cardiac pPLB Ser(16) and the pPLB Ser(16)/PLB ratio in Ob rats. Long-term obesity promotes alterations in diastolic function, most likely due to the reduction of pPLB Ser(16), but does not impair the myocardial Ca(2+) entry and recapture to SR. Copyright © 2014 the American Physiological Society.

Assessment of hemodynamic load components affecting optimization of cardiac resynchronization therapy by lumped parameter mode.

PubMed

Xu, Ke; Butlin, Mark; Avolio, Alberto P

2012-01-01

Timing of biventricular pacing devices employed in cardiac resynchronization therapy (CRT) is a critical determinant of efficacy of the procedure. Optimization is done by maximizing function in terms of arterial pressure (BP) or cardiac output (CO). However, BP and CO are also determined by the hemodynamic load of the pulmonary and systemic vasculature. This study aims to use a lumped parameter circulatory model to assess the influence of the arterial load on the atrio-ventricular (AV) and inter-ventricular (VV) delay for optimal CRT performance.

False dyssynchrony: problem with image-based cardiac functional analysis using x-ray computed tomography

NASA Astrophysics Data System (ADS)

Kidoh, Masafumi; Shen, Zeyang; Suzuki, Yuki; Ciuffo, Luisa; Ashikaga, Hiroshi; Fung, George S. K.; Otake, Yoshito; Zimmerman, Stefan L.; Lima, Joao A. C.; Higuchi, Takahiro; Lee, Okkyun; Sato, Yoshinobu; Becker, Lewis C.; Fishman, Elliot K.; Taguchi, Katsuyuki

2017-03-01

We have developed a digitally synthesized patient which we call "Zach" (Zero millisecond Adjustable Clinical Heart) phantom, which allows for an access to the ground truth and assessment of image-based cardiac functional analysis (CFA) using CT images with clinically realistic settings. The study using Zach phantom revealed a major problem with image-based CFA: "False dyssynchrony." Even though the true motion of wall segments is in synchrony, it may appear to be dyssynchrony with the reconstructed cardiac CT images. It is attributed to how cardiac images are reconstructed and how wall locations are updated over cardiac phases. The presence and the degree of false dyssynchrony may vary from scan-to-scan, which could degrade the accuracy and the repeatability (or precision) of image-based CT-CFA exams.

The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults.

PubMed

Shah, A S; Khoury, P R; Dolan, L M; Ippisch, H M; Urbina, E M; Daniels, S R; Kimball, T R

2011-04-01

We sought to evaluate the effects of obesity and obesity-related type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and diastolic function in adolescents and young adults. Cardiac structure and function were compared by echocardiography in participants who were lean, obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study. Group differences were assessed using ANOVA. Independent determinants of cardiac outcome measures were evaluated with general linear models. Adolescents with obesity and obesity-related type 2 diabetes were found to have abnormal cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05). These two groups also had increased systolic function. Diastolic function decreased from the lean to obese to obese diabetic groups with the lowest diastolic function observed in the obese diabetic group (p < 0.05). Regression analysis showed that group, BMI z score (BMIz), group × BMIz interaction and systolic BP z score (BPz) were significant determinants of cardiac structure, while group, BMIz, systolic BPz, age and fasting glucose were significant determinants of the diastolic function (all p < 0.05). Adolescents with obesity and obesity-related type 2 diabetes demonstrate changes in cardiac geometry consistent with cardiac remodelling. These two groups also demonstrate decreased diastolic function compared with lean controls, with the greatest decrease observed in those with type 2 diabetes. Adults with diastolic dysfunction are known to be at increased risk of progressing to heart failure. Therefore, our findings suggest that adolescents with obesity-related type 2 diabetes may be at increased risk of progressing to early heart failure compared with their obese and lean counterparts.

Cardiac structure and function across the glycemic spectrum in elderly men and women free of prevalent heart disease: the Atherosclerosis Risk In the Community study.

PubMed

Skali, Hicham; Shah, Amil; Gupta, Deepak K; Cheng, Susan; Claggett, Brian; Liu, Jiankang; Bello, Natalie; Aguilar, David; Vardeny, Orly; Matsushita, Kunihiro; Selvin, Elizabeth; Solomon, Scott

2015-05-01

Individuals with diabetes mellitus and pre-diabetes mellitus are at particularly high risk of incident heart failure or death, even after accounting for known confounders. Nevertheless, the extent of impairments in cardiac structure and function in elderly individuals with diabetes mellitus and pre-diabetes mellitus is not well known. We aimed to assess the relationship between echocardiographic measures of cardiac structure and function and dysglycemia. We assessed measures of cardiac structure and function in 4419 participants without prevalent coronary heart disease or heart failure who attended the Atherosclerosis Risk In the Community (ARIC) visit 5 examination (2011-2013) and underwent transthoracic echocardiography (age, 75±6 years; 61% women, 23% black). Subjects were grouped across the dysglycemia spectrum as normal (39%), pre-diabetes mellitus (31%), or diabetes mellitus (30%) based on medical history, antidiabetic medication use, and glycated hemoglobin levels. Glycemic status was related to measures of cardiac structure and function. Worsening dysglycemia was associated with increased left ventricular mass, worse diastolic function, and subtle reduction in left ventricular systolic function (P≤0.01 for all). For every 1% higher glycated hemoglobin, left ventricular mass was higher by 3.0 g (95% confidence interval, 1.5-4.6 g), E/E' by 0.5 (95% confidence interval, 0.4-0.7), and global longitudinal strain by 0.3% (95% confidence interval, 0.2-0.4) in multivariable analyses. In a large contemporary biracial cohort of elderly subjects without prevalent cardiovascular disease or heart failure, dysglycemia was associated with subtle and subclinical alterations of cardiac structure, and left ventricular systolic and diastolic function. It remains unclear whether these are sufficient to explain the heightened risk of heart failure in individuals with diabetes mellitus. © 2015 American Heart Association, Inc.

Relation between the Disability of the Arm, Shoulder and Hand Score and Muscle Strength in Post-Cardiac Surgery Patients

PubMed Central

Kasahara, Yusuke; Hiraki, Koji; Hirano, Yasuyuki; Watanabe, Satoshi

2017-01-01

Background: The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire is a valid and reliable patient-reported outcome measure. DASH can be assessed by self-reported upper extremity disability and symptoms. We aimed to examine the relationship between the physiological outcome of muscle strength and the DASH score after cardiac surgery. Methods: This cross-sectional study assessed 50 consecutive cardiac patients that were undergoing cardiac surgery. Physiological outcomes of handgrip strength and knee extensor muscle strength and the DASH score were measured at one month after cardiac surgery and were assessed. Results were analyzed using Spearman correlation coefficients. Results: The final analysis comprised 43 patients (men: 32, women: 11; age: 62.1 ± 9.1 years; body mass index: 22.1 ± 4.7 kg/m2; left ventricular ejection fraction: 53.5 ± 13.7%). Respective handgrip strength, knee extensor muscle strength, and DASH score were 27.4 ± 8.3 kgf, 1.6 ± 0.4 Nm/kg, and 13.3 ± 12.3, respectively. The DASH score correlated negatively with handgrip strength (r = −0.38, p = 0.01) and with knee extensor muscle strength (r = −0.32, p = 0.04). Conclusion: Physiological outcomes of both handgrip strength and knee extensor muscle strength correlated negatively with the DASH score. The DASH score appears to be a valuable tool with which to assess cardiac patients with poor physiological outcomes, particularly handgrip strength as a measure of upper extremity function, which is probably easier to follow over time than lower extremity function after patients complete cardiac rehabilitation. PMID:29186880

Harmony Behind the Trumped-Shaped Vessel: the Essential Role of the Ductus Venosus in Fetal Medicine.

PubMed

Turan, Sifa; Turan, Ozhan M

2018-03-15

The ductus venosus is a fetal vessel that functions importantly in the transfer of oxygen-and nutrient-rich blood from the umbilical vein to vital organs. Its control under active regulation and its anatomy result in a flow-velocity profile that is typically forward throughout the cardiac cycle. This forward cardiac function reflects afterload, cardiac contractility, compliance, and vascular volume changes. Ductus venosus assessment gives valuable information under different fetal conditions. For example, during first trimester screening, an abnormal ductus venosus measurement changes the screening result. Assessment of ductus venosus in twin-to-twin transfusion syndrome is an essential element of staging. In fetal growth restriction, an abnormal waveform mandates imminent delivery. In this review, we will discuss the role of ductus venosus assessment and its role in antenatal management and outcome prediction in certain fetal conditions throughout pregnancy.

Harmony Behind the Trumped-Shaped Vessel: the Essential Role of the Ductus Venosus in Fetal Medicine

PubMed Central

Turan, Sifa; Turan, Ozhan M.

2018-01-01

The ductus venosus is a fetal vessel that functions importantly in the transfer of oxygen-and nutrient-rich blood from the umbilical vein to vital organs. Its control under active regulation and its anatomy result in a flow-velocity profile that is typically forward throughout the cardiac cycle. This forward cardiac function reflects afterload, cardiac contractility, compliance, and vascular volume changes. Ductus venosus assessment gives valuable information under different fetal conditions. For example, during first trimester screening, an abnormal ductus venosus measurement changes the screening result. Assessment of ductus venosus in twin-to-twin transfusion syndrome is an essential element of staging. In fetal growth restriction, an abnormal waveform mandates imminent delivery. In this review, we will discuss the role of ductus venosus assessment and its role in antenatal management and outcome prediction in certain fetal conditions throughout pregnancy. PMID:29553462

Nandrolone and resistance training induce heart remodeling: role of fetal genes and implications for cardiac pathophysiology.

PubMed

Tanno, Ana Paula; das Neves, Vander José; Rosa, Kaleizu Teodoro; Cunha, Tatiana Sousa; Giordano, Fernanda Cristina Linarello; Calil, Caroline Morini; Guzzoni, Vinicius; Fernandes, Tiago; de Oliveira, Edilamar Menezes; Novaes, Pedro Duarte; Irigoyen, Maria Cláudia; Moura, Maria José Costa Sampaio; Marcondes, Fernanda Klein

2011-10-24

This study was conducted to assess the isolated and combined effects of nandrolone and resistance training on cardiac morphology, function, and mRNA expression of pathological cardiac hypertrophy markers. Wistar rats were randomly divided into four groups and submitted to 6 weeks of treatment with nandrolone and/or resistance training. Cardiac parameters were determined by echocardiography. Heart was analyzed for collagen infiltration. Real-time RT-PCR was used to assess the pathological cardiac hypertrophy markers. Both resistance training and nandrolone induced cardiac hypertrophy. Nandrolone increased the cardiac collagen content, and reduced the cardiac index in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the ratio of maximum early to late transmitral flow velocity in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the alpha-myosin heavy chain gene expression in both non-trained and trained groups, when compared with the respective vehicle-treated groups. Training reduced the beta-myosin heavy chain gene expression in the groups treated with vehicle and nandrolone. Only the association between training and nandrolone increased the expression of the skeletal alpha-actin gene and atrial natriuretic peptide in the left ventricle. This study indicated that nandrolone, whether associated with resistance training or not, induces cardiac hypertrophy, which is associated with enhanced collagen content, re-expression of fetal genes the in left ventricle, and impaired diastolic and systolic function. Copyright © 2011 Elsevier Inc. All rights reserved.

Cardiac rehabilitation and mid-term follow-up after transcatheter aortic valve implantation

PubMed Central

Zanettini, Renzo; Gatto, Gemma; Mori, Ileana; Pozzoni, Maria Beatrice; Pelenghi, Stefano; Martinelli, Luigi; Klugmann, Silvio

2014-01-01

Background Evaluation of patient outcomes following transcatheter aortic valve implantation (TAVI) has usually been based on survival and clinical improvement. Studies on quality of life are limited, and data from comprehensive assessments after the procedure are lacking. Methods Sixty patients referred for cardiac rehabilitation after TAVI underwent in-hospital and after-discharge multidimensional assessments to evaluate clinical, functional, and nutritional statuses, degree of autonomy, cognitive impairment, depression and quality of life. Results On admission to rehabilitation, approximately half of the patients had severe functional impairment and dependence for basic activities of daily living. During their hospital stay, one-third of the patients suffered significant clinical complications and two had to be transferred to the implantation center. Despite this, the overall outcome was very good. All of the remaining patients were clinically stable at discharge and functional status, autonomy and quality of life were improved in most. During a mean follow-up of 540 days (range: 192–738 days), five patients died from noncardiac causes, three were hospitalized for cardiac events, and nine for non cardiac reasons. Functional status and autonomy remained satisfactory in the majority of patients and most continued to live independently. Conclusions Patients referred for rehabilitation after TAVI are often very frail, with a high grade of functional impairment, dependence on others and high risk of clinical complications. During a rehabilitation programme, based on a multidimensional assessment and intervention, most patients showed significant improvement in functional status, quality of life, and autonomy, which remained stable in the majority of subjects during mid-term follow-up. PMID:25593575

Cardiac and renal function in a large cohort of amateur marathon runners.

PubMed

Hewing, Bernd; Schattke, Sebastian; Spethmann, Sebastian; Sanad, Wasiem; Schroeckh, Sabrina; Schimke, Ingolf; Halleck, Fabian; Peters, Harm; Brechtel, Lars; Lock, Jürgen; Baumann, Gert; Dreger, Henryk; Borges, Adrian C; Knebel, Fabian

2015-03-21

Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

In Sickness and in Health: a Literature Review about Function of Social Support within Anxiety and Heart Disease Association

PubMed Central

Zarbo, Cristina; Compare, Angelo; Baldassari, Elena; Bonardi, Alberto; Romagnoni, Claudia

2013-01-01

A narrative review of the major evidence concerning the relationship between anxiety, social support and cardiac disease was conducted. Literature demonstrates that a strict relationship between anxiety, social support and cardiac disease outcomes subsists. However, the function of social support within anxiety and heart disease association remains unclear and needs to further researches to be established. Moreover evidence suggests that it’s the quality of close relationships to play an important role in affecting psychological and physiological health status. The main components that the literature suggests for a better quality of social support and close relationship, and the main assessment measure are presented. Evidence about cardiac rehabilitation programs and the need to assess and intervene on psychological and psychosocial factors is discussed. PMID:24403952

Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association.

PubMed

Donofrio, Mary T; Moon-Grady, Anita J; Hornberger, Lisa K; Copel, Joshua A; Sklansky, Mark S; Abuhamad, Alfred; Cuneo, Bettina F; Huhta, James C; Jonas, Richard A; Krishnan, Anita; Lacey, Stephanie; Lee, Wesley; Michelfelder, Erik C; Rempel, Gwen R; Silverman, Norman H; Spray, Thomas L; Strasburger, Janette F; Tworetzky, Wayne; Rychik, Jack

2014-05-27

The goal of this statement is to review available literature and to put forth a scientific statement on the current practice of fetal cardiac medicine, including the diagnosis and management of fetal cardiovascular disease. A writing group appointed by the American Heart Association reviewed the available literature pertaining to topics relevant to fetal cardiac medicine, including the diagnosis of congenital heart disease and arrhythmias, assessment of cardiac function and the cardiovascular system, and available treatment options. The American College of Cardiology/American Heart Association classification of recommendations and level of evidence for practice guidelines were applied to the current practice of fetal cardiac medicine. Recommendations relating to the specifics of fetal diagnosis, including the timing of referral for study, indications for referral, and experience suggested for performance and interpretation of studies, are presented. The components of a fetal echocardiogram are described in detail, including descriptions of the assessment of cardiac anatomy, cardiac function, and rhythm. Complementary modalities for fetal cardiac assessment are reviewed, including the use of advanced ultrasound techniques, fetal magnetic resonance imaging, and fetal magnetocardiography and electrocardiography for rhythm assessment. Models for parental counseling and a discussion of parental stress and depression assessments are reviewed. Available fetal therapies, including medical management for arrhythmias or heart failure and closed or open intervention for diseases affecting the cardiovascular system such as twin-twin transfusion syndrome, lung masses, and vascular tumors, are highlighted. Catheter-based intervention strategies to prevent the progression of disease in utero are also discussed. Recommendations for delivery planning strategies for fetuses with congenital heart disease including models based on classification of disease severity and delivery room treatment will be highlighted. Outcome assessment is reviewed to show the benefit of prenatal diagnosis and management as they affect outcome for babies with congenital heart disease. Fetal cardiac medicine has evolved considerably over the past 2 decades, predominantly in response to advances in imaging technology and innovations in therapies. The diagnosis of cardiac disease in the fetus is mostly made with ultrasound; however, new technologies, including 3- and 4-dimensional echocardiography, magnetic resonance imaging, and fetal electrocardiography and magnetocardiography, are available. Medical and interventional treatments for select diseases and strategies for delivery room care enable stabilization of high-risk fetuses and contribute to improved outcomes. This statement highlights what is currently known and recommended on the basis of evidence and experience in the rapidly advancing and highly specialized field of fetal cardiac care. © 2014 American Heart Association, Inc.

Reduced cardiac vagal activity in obese children and adolescents.

PubMed

Dangardt, Frida; Volkmann, Reinhard; Chen, Yun; Osika, Walter; Mårild, Staffan; Friberg, Peter

2011-03-01

  Obese children present with various cardiovascular risk factors affecting their future health. In adults, cardiac autonomic function is a major risk factor, predicting cardiovascular morbidity and mortality. We hypothesized that obese children and adolescents had a lower cardiac vagal activity than lean subjects. We measured cardiac spontaneous baroreflex sensitivity (BRS), reflecting the dynamic regulation of cardiac vagal function, in large groups of obese and lean young individuals.   Cardiac BRS, using the sequence approach, was assessed in 120 obese (59 girls), 43 overweight (23 girls) and 148 lean subjects (78 girls). Obese subjects showed a decreased BRS compared to both overweight and lean subjects [16±7 versus 21±9 (P<0·01) and 22±10 ms per mmHg (P<0·0001), respectively]. The differences remained after correcting for age, gender and pubertal status.   Children with obesity had low vagal activity at rest, and there was no gender difference. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Modular assembly of thick multifunctional cardiac patches

PubMed Central

Fleischer, Sharon; Shapira, Assaf; Feiner, Ron; Dvir, Tal

2017-01-01

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues. PMID:28167795

Cardiac sarcoidosis: challenges in clinical practice.

PubMed

Bakker, Anne L; Grutters, Jan C; Keijsers, Ruth G; Post, Martijn C

2017-09-01

To address the current recommendations for screening, diagnosis, and treatment of cardiac sarcoidosis and the difficulties to put these recommendations into clinical practice. The incidence of cardiac sarcoidosis appears to be higher than earlier reported, probably because of improved imaging techniques. Late gadolinium enhancement with cardiac MRI (LGE-CMR) and fluorodeoxyglucose positron emission tomography obtained a central role in the diagnostic algorithm and monitoring of disease activity. New techniques are being investigated: T1 and T2 mapping for early detection in CMR, a sarcoid-specific tracer in PET, integrated positron emission tomography/MRI scanners, and assessment of scar with LGE in cardiac computed tomography. Isolated cardiac sarcoidosis is an increasingly recognized phenotype, but still an enormous challenge in clinical practice. The prognostic value of (and extent of) LGE-CMR should be taken into account for risk assessment and internal cardiac defbrillator therapy, even in patients with preserved left ventricular function. Unfortunately, randomized controlled trials to guide immunosuppressive therapy are still lacking. A multidisciplinary approach to diagnose and treat cardiac sarcoidosis patients in specialized centers is strongly recommendable. Cardiac sarcoidosis is increasingly recognized because of improved imaging techniques; however, treatment of cardiac sarcoidosis is still mainly based on expert opinion.

A novel cardiac MR chamber volume model for mechanical dyssynchrony assessment

NASA Astrophysics Data System (ADS)

Song, Ting; Fung, Maggie; Stainsby, Jeffrey A.; Hood, Maureen N.; Ho, Vincent B.

2009-02-01

A novel cardiac chamber volume model is proposed for the assessment of left ventricular mechanical dyssynchrony. The tool is potentially useful for assessment of regional cardiac function and identification of mechanical dyssynchrony on MRI. Dyssynchrony results typically from a contraction delay between one or more individual left ventricular segments, which in turn leads to inefficient ventricular function and ultimately heart failure. Cardiac resynchronization therapy has emerged as an electrical treatment of choice for heart failure patients with dyssynchrony. Prior MRI techniques have relied on assessments of actual cardiac wall changes either using standard cine MR images or specialized pulse sequences. In this abstract, we detail a semi-automated method that evaluates dyssynchrony based on segmental volumetric analysis of the left ventricular (LV) chamber as illustrated on standard cine MR images. Twelve sectors each were chosen for the basal and mid-ventricular slices and 8 sectors were chosen for apical slices for a total of 32 sectors. For each slice (i.e. basal, mid and apical), a systolic dyssynchrony index (SDI) was measured. SDI, a parameter used for 3D echocardiographic analysis of dyssynchrony, was defined as the corrected standard deviation of the time at which minimal volume is reached in each sector. The SDI measurement of a healthy volunteer was 3.54%. In a patient with acute myocardial infarction, the SDI measurements 10.98%, 16.57% and 1.41% for basal, mid-ventricular and apical LV slices, respectively. Based on published 3D echocardiogram reference threshold values, the patient's SDI corresponds to moderate basal dysfunction, severe mid-ventricular dysfunction, and normal apical LV function, which were confirmed on echocardiography. The LV chamber segmental volume analysis model and SDI is feasible using standard cine MR data and may provide more reliable assessment of patients with dyssynchrony especially if the LV myocardium is thin or if the MR images have spatial resolution insufficient for proper resolution of wall thickness-features problematic for dyssynchrony assessment using existing MR techniques.

Rationale and Design of the Echocardiographic Study of Hispanics/Latinos (ECHO-SOL).

PubMed

Rodriguez, Carlos J; Dharod, Ajay; Allison, Matthew A; Shah, Sanjiv J; Hurwitz, Barry; Bangdiwala, Shrikant I; Gonzalez, Franklyn; Kitzman, Dalane; Gillam, Linda; Spevack, Daniel; Dadhania, Rupal; Langdon, Sarah; Kaplan, Robert

2015-01-01

Information regarding the prevalence and determinants of cardiac structure and function (systolic and diastolic) among the various Hispanic background groups in the United States is limited. The Echocardiographic Study of Latinos (ECHO-SOL) ancillary study recruited 1,824 participants through a stratified-sampling process representative of the population-based Hispanic Communities Health Study - Study of Latinos (HCHS-SOL) across four sites (Bronx, NY; Chicago, Ill; San Diego, Calif; Miami, Fla). The HCHS-SOL baseline cohort did not include an echo exam. ECHO-SOL added the echocardiographic assessment of cardiac structure and function to an array of existing HCHS-SOL baseline clinical, psychosocial, and socioeconomic data and provides sufficient statistical power for comparisons among the Hispanic subgroups. Standard two-dimensional (2D) echocardiography protocol, including M-mode, spectral, color and tissue Doppler study was performed. The main objectives were to: 1) characterize cardiac structure and function and its determinants among Hispanics and Hispanic subgroups; and 2) determine the contributions of specific psychosocial factors (acculturation and familismo) to cardiac structure and function among Hispanics. We describe the design, methods and rationale of currently the largest and most comprehensive study of cardiac structure and function exclusively among US Hispanics. ECHO-SOL aims to enhance our understanding of Hispanic cardiovascular health as well as help untangle the relative importance of Hispanic subgroup heterogeneity and sociocultural factors on cardiac structure and function.

Endocardial left ventricle feature tracking and reconstruction from tri-plane trans-esophageal echocardiography data

NASA Astrophysics Data System (ADS)

Dangi, Shusil; Ben-Zikri, Yehuda K.; Cahill, Nathan; Schwarz, Karl Q.; Linte, Cristian A.

2015-03-01

Two-dimensional (2D) ultrasound (US) has been the clinical standard for over two decades for monitoring and assessing cardiac function and providing support via intra-operative visualization and guidance for minimally invasive cardiac interventions. Developments in three-dimensional (3D) image acquisition and transducer design and technology have revolutionized echocardiography imaging enabling both real-time 3D trans-esophageal and intra-cardiac image acquisition. However, in most cases the clinicians do not access the entire 3D image volume when analyzing the data, rather they focus on several key views that render the cardiac anatomy of interest during the US imaging exam. This approach enables image acquisition at a much higher spatial and temporal resolution. Two such common approaches are the bi-plane and tri-plane data acquisition protocols; as their name states, the former comprises two orthogonal image views, while the latter depicts the cardiac anatomy based on three co-axially intersecting views spaced at 600 to one another. Since cardiac anatomy is continuously changing, the intra-operative anatomy depicted using real-time US imaging also needs to be updated by tracking the key features of interest and endocardial left ventricle (LV) boundaries. Therefore, rapid automatic feature tracking in US images is critical for three reasons: 1) to perform cardiac function assessment; 2) to identify location of surgical targets for accurate tool to target navigation and on-target instrument positioning; and 3) to enable pre- to intra-op image registration as a means to fuse pre-op CT or MR images used during planning with intra-operative images for enhanced guidance. In this paper we utilize monogenic filtering, graph-cut based segmentation and robust spline smoothing in a combined work flow to process the acquired tri-plane TEE time series US images and demonstrate robust and accurate tracking of the LV endocardial features. We reconstruct the endocardial LV geometry using the tri-plane contours and spline interpolation, and assess the accuracy of the proposed work flow against gold-standard results from the GE Echopac PC clinical software according to quantitative clinical LV characterization parameters, such as the length, circumference, area and volume. Our proposed combined work flow leads to consistent, rapid and automated identification of the LV endocardium, suitable for intra-operative applications and "on-the-fly" computer-assisted assessment of ejection fraction for cardiac function monitoring.Two-dimensional (2D) ultrasound (US) has been the clinical standard for over two decades for monitoring and assessing cardiac function and providing support via intra-operative visualization and guidance for minimally invasive cardiac interventions. Developments in three-dimensional (3D) image acquisition and transducer design and technology have revolutionized echocardiography imaging enabling both real-time 3D trans-esophageal and intra-cardiac image acquisition. However, in most cases the clinicians do not access the entire 3D image volume when analyzing the data, rather they focus on several key views that render the cardiac anatomy of interest during the US imaging exam. This approach enables image acquisition at a much higher spatial and temporal resolution. Two such common approaches are the bi-plane and tri-plane data acquisition protocols; as their name states, the former comprises two orthogonal image views, while the latter depicts the cardiac anatomy based on three co-axially intersecting views spaced at 600 to one another. Since cardiac anatomy is continuously changing, the intra-operative anatomy depicted using real-time US imaging also needs to be updated by tracking the key features of interest and endocardial left ventricle (LV) boundaries. Therefore, rapid automatic feature tracking in US images is critical for three reasons: 1) to perform cardiac function assessment; 2) to identify location of surgical targets for accurate tool to target navigation and on-target instrument positioning; and 3) to enable pre- to intra-op image registration as a means to fuse pre-op CT or MR images used during planning with intra-operative images for enhanced guidance. In this paper we utilize monogenic filtering, graph-cut based segmentation and robust spline smoothing in a combined work flow to process the acquired tri-plane TEE time series US images and demonstrate robust and accurate tracking of the LV endocardial features. We reconstruct the endocardial LV geometry using the tri-plane contours and spline interpolation, and assess the accuracy of the proposed work flow against gold-standard results from the GE Echopac PC clinical software according to quantitative clinical LV characterization parameters, such as the length, circumference, area and volume. Our proposed combined work flow leads to consistent, rapid and automated identification of the LV endocardium, suitable for intra-operative applications and on-the- y" computer-assisted assessment of ejection fraction for cardiac function monitoring.

Effect of hydration status on atrial and ventricular volumes and function in healthy adult volunteers.

PubMed

Schantz, Daryl I; Dragulescu, Andreea; Memauri, Brett; Grotenhuis, Heynric B; Seed, Mike; Grosse-Wortmann, Lars

2016-10-01

Assessment of cardiac chamber volumes is a fundamental part of cardiac magnetic resonance (CMR) imaging. While the effects of inter- and intraobserver variability have been studied and have a recognized effect on the comparability of serial cardiac MR imaging studies, the effect of differences in hydration status has not been evaluated. To evaluate the effects of volume administration on cardiac chamber volumes. Thirteen healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber volumes after an overnight fast. They were then given two saline boluses of 10 ml/kg of body weight and the cardiac MR was repeated immediately after each bolus. From the baseline scan to the final scan there was a significant increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes increased 8.0%, from 61.1 to 66.0 ml/m2 (P<0.001), and left atrial volumes increased 10.0%, from 50.0 to 55.0 ml/m2 (P<0.001). Right ventricular volumes increased 6.0%, from 91.1 to 96.5 ml/m2 (P<0.001), and left ventricular volumes increased 3.2%, from 87.0 to 89.8 ml/m2 (P<0.001). Hydration status has a significant effect on the end-diastolic volumes of all cardiac chambers assessed by cardiac MR. Thus, hydration represents a "variable" that should be taken into account when assessing cardiac chamber volumes, especially when performing serial imaging studies in a patient.

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

PubMed

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

2008-06-01

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

Skin temperature and core-peripheral temperature gradient as markers of hemodynamic status in critically ill patients: a review.

PubMed

Schey, Bernadette M; Williams, David Y; Bucknall, Tracey

2010-01-01

To examine the evidential basis underpinning the monitoring of skin temperature and core-peripheral temperature gradient as elements of hemodynamic assessment in critically ill and adult cardiac surgical patients. Twenty-six studies examining the efficacy of skin temperature or temperature gradient as markers of hemodynamic status were selected as part of an integrative review. Evidence pertaining to the efficacy of these parameters as markers of cardiac function is equivocal and has not been well appraised in the adult cardiac surgical population. Skin temperature and systemic vascular resistance are also affected by factors other than cardiac output. Skin temperature and core-peripheral temperature gradient should not be considered in isolation from other hemodynamic parameters when assessing cardiac status until they are validated by further large-scale prospective studies. 2010. Published by Mosby, Inc.

Morbidity, mortality and economic burden of renal impairment in cardiac intensive care.

PubMed

Chew, D P; Astley, C; Molloy, D; Vaile, J; De Pasquale, C G; Aylward, P

2006-03-01

Moderate to severe impairment of renal function has emerged as a potent risk factor for adverse short- and long-term outcomes among patients presenting with cardiac disease. We sought to define the clinical, late mortality and economic burden of this risk factor among patients presenting to cardiac intensive care. A clinical audit of patients presenting to cardiac intensive care was undertaken between July 2002 and June 2003. All patients presenting with cardiac diagnoses were included in the study. Baseline creatinine levels were assessed in all patients. Late mortality was assessed by the interrogation of the National Death Register. Renal impairment was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2, as calculated by the Modified Diet in Renal Disease formula. In-hospital and late outcomes were compared by Cox proportional hazards modelling, adjusting for known confounders. A matched analysis and attributable risk calculation were undertaken to assess the proportion of late mortality accounted for by impairment of renal function and other known negative prognostic factors. The in-hospital total cost associated with renal impairment was assessed by linear regression. Glomerular filtration rate <60 mL/min per 1.73 m2 was evident in 33.0% of this population. Among these patients, in-hospital and late mortality were substantially increased: risk ratio 13.2; 95% CI 3.0-58.1; P < 0.001 and hazard ratio 6.2; 95% CI 3.6-10.7; P < 0.001, respectively. In matched analysis, renal impairment to this level was associated with 42.1% of all the late deaths observed. Paradoxically, patients with renal impairment were more conservatively managed, but their hospitalizations were associated with an excess adjusted in-hospital cost of $A1676. Impaired renal function is associated with a striking clinical and economic burden among patients presenting to cardiac intensive care. As a marker for future risk, renal function accounts for a substantial proportion of the burden of late mortality. The burden of risk suggests a greater potential opportunity for improvement of outcomes through optimisation of therapeutic strategies.

Executive Function and Theory of Mind in School-Aged Children after Neonatal Corrective Cardiac Surgery for Transposition of the Great Arteries

ERIC Educational Resources Information Center

Calderon, Johanna; Bonnet, Damien; Courtin, Cyril; Concordet, Susan; Plumet, Marie-Helene; Angeard, Nathalie

2010-01-01

Aim: Cardiac malformations resulting in cyanosis, such as transposition of the great arteries (TGA), have been associated with neurodevelopmental dysfunction. The purpose of this study was to assess, for the first time, theory of mind (ToM), which is a key component of social cognition and executive functions in school-aged children with TGA.…

Single-Dose Intracardiac Injection of Pro-Regenerative MicroRNAs Improves Cardiac Function After Myocardial Infarction.

PubMed

Lesizza, Pierluigi; Prosdocimo, Giulia; Martinelli, Valentina; Sinagra, Gianfranco; Zacchigna, Serena; Giacca, Mauro

2017-04-14

Recent evidence indicates that a few human microRNAs (miRNAs), in particular hsa-miR-199a-3p and hsa-miR-590-3p, stimulate proliferation of cardiomyocytes and, once expressed in the mouse heart using viral vectors, induce cardiac regeneration after myocardial infarction. Viral vectors, however, are not devoid of safety issues and, more notably, drive expression of the encoded miRNAs for indefinite periods of time, which might not be desirable in light of human therapeutic application. As an alternative to the use of viral vectors, we wanted to assess the efficacy of synthetic miRNA mimics in inducing myocardial repair after single intracardiac injection using synthetic lipid formulations. We comparatively analyzed the efficacy of different lipid formulations in delivering hsa-miR-199a-3p and hsa-miR-590-3p both in primary neonatal mouse cardiomyocytes and in vivo. We established a transfection protocol allowing persistence of these 2 mimics for at least 12 days after a single intracardiac injection, with minimal dispersion to other organs and long-term preservation of miRNA functional activity, as assessed by monitoring the expression of 2 mRNA targets. Administration of this synthetic formulation immediately after myocardial infarction in mice resulted in marked reduction of infarct size and persistent recovery of cardiac function. A single administration of synthetic miRNA-lipid formulations is sufficient to stimulate cardiac repair and restoration of cardiac function. © 2017 American Heart Association, Inc.

Magnetic resonance imaging reveals elevated aortic pulse wave velocity in obese and overweight adolescents.

PubMed

Caterini, J E; Banks, L; Wells, G D; Cifra, B; Slorach, C; McCrindle, B W; Seed, M

2017-12-01

The aortic pulse wave velocity (PWV) measured via cardiac magnetic resonance (CMR) can be used to non-invasively assess changes in arterial stiffness and potential underlying vascular dysfunction. This technique could unmask early arterial dysfunction in overweight and obese youth at risk for cardiovascular disease. We sought to determine the association between vascular stiffness, percentage body fat, body mass index (BMI), and cardiac function in adolescents across the weight spectrum through both CMR and standard applanation tonometry (AT)-based PWV measurements. PWV and left-ventricular cardiac function were assessed using 3.0 T CMR in obese and overweight (OB/OW) participants (n = 12) and controls (n = 7). PWV was also estimated via carotid-femoral AT. OB/OW participants did not differ from healthy-weight controls regarding cardiometabolic risk factors or physical activity levels, but there was a trend towards higher levels of triglycerides in obese/overweight participants (P = 0.07). Mean PWV was higher in obese participants when corrected for age and sex (P = 0.01), and was positively associated with BMI (β = 0.51, P = 0.02). PWV estimated through AT was not significantly different between groups. Cardiac function measured by left-ventricular ejection fraction z-score was inversely associated with mean PWV (β = -0.57, P = 0.026). Increasing arterial stiffness and decreasing cardiac function were evident among our overweight and obese cohort. PWV estimated by CMR could detect early increases in arterial stiffness vs. traditional AT measurements of PWV. © 2017 World Obesity Federation.

Effects of testosterone and nandrolone on cardiac function: a randomized, placebo-controlled study.

PubMed

Chung, T; Kelleher, S; Liu, P Y; Conway, A J; Kritharides, L; Handelsman, D J

2007-02-01

Androgens have striking effects on skeletal muscle, but the effects on human cardiac muscle function are not well defined, neither has the role of metabolic activation (aromatization, 5alpha reduction) of testosterone on cardiac muscle been directly studied. To assess the effects of testosterone and nandrolone, a non-amplifiable and non-aromatizable pure androgen, on cardiac muscle function in healthy young men. Double-blind, randomized, placebo-controlled, three-arm parallel group clinical trial. Ambulatory care research centre. Healthy young men randomized into three groups of 10 men. Weekly intramuscular injections of testosterone (200 mg mixed esters), nandrolone (200 mg nandrolone decanoate) or matching (2 ml arachis oil vehicle) placebo for 4 weeks. Comprehensive measures of cardiac muscle function involving transthoracic cardiac echocardiography measuring myocardial tissue velocity, peak systolic strain and strain rates, and bioimpedance measurement of cardiac output and systematic vascular resistance. Left ventricular (LV) function (LV ejection fraction, LV modified TEI index), right ventricular (RV) function (ejection area, tricuspid annular systolic planar motion, RV modified TEI index) as well as cardiac afterload (mean arterial pressure, systemic vascular resistance) and overall cardiac contractility (stroke volume, cardiac output) were within age- and gender-specific reference ranges and were not significantly (P < 0.05) altered by either androgen or placebo over 4 weeks of treatment. Minor changes remaining within normal range were observed solely within the testosterone group for: increased LV end-systolic diameter (30 +/- 7 vs. 33 +/- 5 mm, P = 0.04) and RV end-systolic area (12.8 +/- 1.3 vs. 14.6 +/- 3.3 cm(2), P = 0.04), reduced LV diastolic septal velocity (Em, 9.5 +/- 2.6 vs. 8.7 +/- 2.0 cm/s, P = 0.006), increased LV filling pressure (E/Em ratio, 7.1 +/- 1.6 vs. 8.3 +/- 1.8, P = 0.02) and shortened PR interval on the electrocardiogram (167 +/- 13 vs. 154 +/- 12, P = 0.03). Four weeks of treatment with testosterone or nandrolone had no beneficial or adverse effects compared with placebo on cardiac function in healthy young men.

Cardiac telomere length in heart development, function, and disease.

PubMed

Booth, S A; Charchar, F J

2017-07-01

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

The day/night proteome in the murine heart.

PubMed

Podobed, Peter; Pyle, W Glen; Ackloo, Suzanne; Alibhai, Faisal J; Tsimakouridze, Elena V; Ratcliffe, William F; Mackay, Allison; Simpson, Jeremy; Wright, David C; Kirby, Gordon M; Young, Martin E; Martino, Tami A

2014-07-15

Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function.

The effects of malnutrition on cardiac function in African children.

PubMed

Silverman, Jonathan A; Chimalizeni, Yamikani; Hawes, Stephen E; Wolf, Elizabeth R; Batra, Maneesh; Khofi, Harriet; Molyneux, Elizabeth M

2016-02-01

Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. Prospective cross-sectional study. Public referral hospital in Blantyre, Malawi. We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The day/night proteome in the murine heart

PubMed Central

Podobed, Peter; Pyle, W. Glen; Ackloo, Suzanne; Alibhai, Faisal J.; Tsimakouridze, Elena V.; Ratcliffe, William F.; Mackay, Allison; Simpson, Jeremy; Wright, David C.; Kirby, Gordon M.; Young, Martin E.

2014-01-01

Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function. PMID:24789993

Pyridostigmine ameliorates cardiac remodeling induced by myocardial infarction via inhibition of the transforming growth factor-β1/TGF-β1-activated kinase pathway.

PubMed

Lu, Yi; Liu, Jin-Jun; Bi, Xue-Yuan; Yu, Xiao-Jiang; Kong, Shan-Shan; Qin, Fang-Fang; Zhou, Jun; Zang, Wei-Jin

2014-05-01

Autonomic imbalance characterized by sympathetic predominance coinciding with diminished vagal activity is an independent risk factor in cardiovascular diseases. Several studies show that vagus nerve stimulation exerted beneficial effects on cardiac function and survival. In this study, we investigated the vagomimetic effect of pyridostigmine on left ventricular (LV) remodeling in rats after myocardial infarction. After myocardial infarction, surviving rats were treated with or without pyridostigmine (31 mg·kg⁻¹·d⁻¹) for 2 weeks, and hemodynamic parameters were measured. LV tissue was used to assess infarct size and interstitial fibrosis by Masson's trichrome and 0.1% picrosirius red staining. Protein expression of heart tissues was used to assess the efficacy of the treatment. Pyridostigmine markedly reduced myocardial infarct size and improved cardiac diastolic function. These improvements were accompanied with a significant decrease in matrix metalloproteinase-2 expression and collagen deposition. Additionally, pyridostigmine inhibited both transforming growth factor-β1 (TGF-β1) and TGF-β1-activated kinase expression in hearts postmyocardial infarction. Thus, pyridostigmine reduces collagen deposition, attenuates cardiac fibrosis, and improves LV diastolic function after myocardial infarction via TGF-β1/TGF-β1-activated kinase pathway inhibition.

Necessity of angiotensin-converting enzyme-related gene for cardiac functions and longevity of Drosophila melanogaster assessed by optical coherence tomography

NASA Astrophysics Data System (ADS)

Liao, Fang-Tsu; Chang, Cheng-Yi; Su, Ming-Tsan; Kuo, Wen-Chuan

2014-01-01

Prior studies have established the necessity of an angiotensin-converting enzyme-related (ACER) gene for heart morphogenesis of Drosophila. Nevertheless, the physiology of ACER has yet to be comprehensively understood. Herein, we employed RNA interference to down-regulate the expression of ACER in Drosophila's heart and swept source optical coherence tomography to assess whether ACER is required for cardiac functions in living adult flies. Several contractile parameters of Drosophila heart, including the heart rate (HR), end-diastolic diameter (EDD), end-systolic diameter (ESD), percent fractional shortening (%FS), and stress-induced cardiac performance, are shown, which are age dependent. These age-dependent cardiac functions declined significantly when ACER was down-regulated. Moreover, the lifespans of ACER knock-down flies were significantly shorter than those of wild-type control flies. Thus, we posit that ACER, the Drosophila ortholog of mammalian angiotensin-converting enzyme 2 (ACE2), is essential for both heart physiology and longevity of animals. Since mammalian ACE2 controls many cardiovascular physiological features and is implicated in cardiomyopathies, our findings that ACER plays conserved roles in genetically tractable animals will pave the way for uncovering the genetic pathway that controls the renin-angiotensin system.

The left heart can only be as good as the right heart: determinants of function and dysfunction of the right ventricle.

PubMed

Magder, Sheldon

2007-12-01

Discussions of cardiac physiology and pathophysiology most often emphasise the function of the left heart. However, right heart dysfunction plays an important role in critically ill patients and is often not recognised. This is probably because the role of the right ventricle is for generating flow more than pressure, and flow is not easy to evaluate. Of importance, when right ventricular function limits cardiac output, assessing left ventricular function gives little indication of overall cardiac performance. It has recently become evident that the right ventricle also has different genetic origins and characteristics from the left ventricle. The right and left ventricles interact through series effects, diastolic interactions and systolic interactions. The mechanisms of these, and their physiological and pathological significance are discussed.

Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in Pathological Remodeling.

PubMed

Zhao, Rong-Rong; Ackers-Johnson, Matthew; Stenzig, Justus; Chen, Chen; Ding, Tao; Zhou, Yue; Wang, Peipei; Ng, Shi Ling; Li, Peter Y; Teo, Gavin; Rudd, Pauline M; Fawcett, James W; Foo, Roger S Y

2018-06-05

Heart failure is a leading cause of mortality and morbidity, and the search for novel therapeutic approaches continues. In the monogenic disease mucopolysaccharidosis VI, loss-of-function mutations in arylsulfatase B lead to myocardial accumulation of chondroitin sulfate (CS) glycosaminoglycans, manifesting as myriad cardiac symptoms. Here, we studied changes in myocardial CS in nonmucopolysaccharidosis failing hearts and assessed its generic role in pathological cardiac remodeling. Healthy and diseased human and rat left ventricles were subjected to histological and immunostaining methods to analyze glycosaminoglycan distribution. Glycosaminoglycans were extracted and analyzed for quantitative and compositional changes with Alcian blue assay and liquid chromatography-mass spectrometry. Expression changes in 20 CS-related genes were studied in 3 primary human cardiac cell types and THP-1-derived macrophages under each of 9 in vitro stimulatory conditions. In 2 rat models of pathological remodeling induced by transverse aortic constriction or isoprenaline infusion, recombinant human arylsulfatase B (rhASB), clinically used as enzyme replacement therapy in mucopolysaccharidosis VI, was administered intravenously for 7 or 5 weeks, respectively. Cardiac function, myocardial fibrosis, and inflammation were assessed by echocardiography and histology. CS-interacting molecules were assessed with surface plasmon resonance, and a mechanism of action was verified in vitro. Failing human hearts displayed significant perivascular and interstitial CS accumulation, particularly in regions of intense fibrosis. Relative composition of CS disaccharides remained unchanged. Transforming growth factor-β induced CS upregulation in cardiac fibroblasts. CS accumulation was also observed in both the pressure-overload and the isoprenaline models of pathological remodeling in rats. Early treatment with rhASB in the transverse aortic constriction model and delayed treatment in the isoprenaline model proved rhASB to be effective at preventing cardiac deterioration and augmenting functional recovery. Functional improvement was accompanied by reduced myocardial inflammation and overall fibrosis. Tumor necrosis factor-α was identified as a direct binding partner of CS glycosaminoglycan chains, and rhASB reduced tumor necrosis factor-α-induced inflammatory gene activation in vitro in endothelial cells and macrophages. CS glycosaminoglycans accumulate during cardiac pathological remodeling and mediate myocardial inflammation and fibrosis. rhASB targets CS effectively as a novel therapeutic approach for the treatment of heart failure. © 2018 American Heart Association, Inc.

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

PubMed Central

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

2016-01-01

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats.

PubMed

Lu, Yi; Wu, Qing; Liu, Long-Zhu; Yu, Xiao-Jiang; Liu, Jin-Jun; Li, Man-Xiang; Zang, Wei-Jin

2018-04-01

Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

In vivo imaging of the Drosophila Melanogaster heart using a novel optical coherence tomography microscope

NASA Astrophysics Data System (ADS)

Izatt, Susan D.; Choma, Michael A.; Israel, Steven; Wessells, Robert J.; Bodmer, Rolf; Izatt, Joseph A.

2005-03-01

Real time in vivo optical coherence tomography (OCT) imaging of the adult fruit fly Drosophila melanogaster heart using a newly designed OCT microscope allows accurate assessment of cardiac anatomy and function. D. melanogaster has been used extensively in genetic research for over a century, but in vivo evaluation of the heart has been limited by available imaging technology. The ability to assess phenotypic changes with micrometer-scale resolution noninvasively in genetic models such as D. melanogaster is needed in the advancing fields of developmental biology and genetics. We have developed a dedicated small animal OCT imaging system incorporating a state-of-the-art, real time OCT scanner integrated into a standard stereo zoom microscope which allows for simultaneous OCT and video imaging. System capabilities include A-scan, B-scan, and M-scan imaging as well as automated 3D volumetric acquisition and visualization. Transverse and sagittal B-mode scans of the four chambered D. melanogaster heart have been obtained with the OCT microscope and are consistent with detailed anatomical studies from the literature. Further analysis by M-mode scanning is currently under way to assess cardiac function as a function of age and sex by determination of shortening fraction and ejection fraction. These studies create control cardiac data on the wild type D. melanogaster, allowing subsequent evaluation of phenotypic cardiac changes in this model after regulated genetic mutation.

Cardiac index is associated with brain aging: the Framingham Heart Study.

PubMed

Jefferson, Angela L; Himali, Jayandra J; Beiser, Alexa S; Au, Rhoda; Massaro, Joseph M; Seshadri, Sudha; Gona, Philimon; Salton, Carol J; DeCarli, Charles; O'Donnell, Christopher J; Benjamin, Emelia J; Wolf, Philip A; Manning, Warren J

2010-08-17

Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61+/-9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values >2.92). Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.

Cardiac index is associated with brain aging: The Framingham Heart Study

PubMed Central

Jefferson, Angela L.; Himali, Jayandra J.; Beiser, Alexa S.; Au, Rhoda; Massaro, Joseph M.; Seshadri, Sudha; Gona, Philimon; Salton, Carol J.; DeCarli, Charles; O’Donnell, Christopher J.; Benjamin, Emelia J.; Wolf, Philip A.; Manning, Warren J.

2010-01-01

Background Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease (CVD), theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with pre-clinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer’s disease in the community. Methods and Results Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free from clinical stroke, transient ischemic attack, or dementia (61±9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent CVD were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post-hoc comparisons revealed that participants in the bottom cardiac index tertile (values<2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values>2.92). Conclusions Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging. PMID:20679552

Cardiac Autonomic Control in Individuals With Down Syndrome

ERIC Educational Resources Information Center

Goulopoulou, Styliani; Baynard, Tracy; Collier, Scott; Giannopoulou, Ifigenia; Figueroa, Arturo; Beets, Michael; Pitetti, Kenneth; Fernhall, Bo

2006-01-01

Our goal in this study was to compare cardiac autonomic control at rest between 50 individuals with Down syndrome and 24 control participants without disabilities. Resting autonomic function was assessed using analysis of heart rate variability. Participants with Down syndrome had reduced total heart rate variability, which indicates possible…

Cardiac Rehabilitation. A Handbook for Vocational Rehabilitation Counselors.

ERIC Educational Resources Information Center

Brammell, H. L.; And Others

Basic information about heart disease and functional capacity assessment and its application to activity/job counseling are presented in this handbook for vocational rehabilitation counselors. Sections include the following: impact of heart disease; basic anatomy and physiology (e.g., the heart, pulmonary circulation, causes of cardiac pain, and…

Oil Exposure Impairs In Situ Cardiac Function in Response to β-Adrenergic Stimulation in Cobia (Rachycentron canadum).

PubMed

Cox, Georgina K; Crossley, Dane A; Stieglitz, John D; Heuer, Rachael M; Benetti, Daniel D; Grosell, Martin

2017-12-19

Aqueous crude oil spills expose fish to varying concentrations of dissolved polycyclic aromatic hydrocarbons (PAHs), which can have lethal and sublethal effects. The heart is particularly vulnerable in early life stages, as PAH toxicity causes developmental cardiac abnormalities and impaired cardiovascular function. However, cardiac responses of juvenile and adult fish to acute oil exposure remain poorly understood. We sought to assess cardiac function in a pelagic fish species, the cobia (Rachycentron canadum), following acute (24 h) exposure to two ecologically relevant levels of dissolved PAHs. Cardiac power output (CPO) was used to quantify cardiovascular performance using an in situ heart preparation. Cardiovascular performance was varied using multiple concentrations of the β-adrenoceptor agonist isoproterenol (ISO) and by varying afterload pressures. Oil exposure adversely affected CPO with control fish achieving maximum CPO's (4 mW g -1 Mv) greater than that of oil-exposed fish (1 mW g -1 Mv) at ISO concentrations of 1 × 10 -6 M. However, the highest concentration of ISO (1 × 10 -5 M) rescued cardiac function. This indicates an interactive effect between oil-exposure and β-adrenergic stimulation and suggests if animals achieve very large increases in β-adrenergic stimulation it could play a compensatory role that may mitigate some adverse effects of oil-exposure in vivo.

Transesophageal echocardiography as an alternative for the assessment of the trauma and critical care patient.

PubMed

Rose, David D

2003-06-01

Transesophageal echocardiography was first described and used to monitor cardiac function in 1976. Initially adopted by cardiac anesthesiologists and cardiologists, it has gained acceptance as an important diagnostic tool in the monitoring and assessment of cardiac status in the critically ill and trauma patient population. Comparative data suggest that transesophageal echocardiography provides rapid real-time noninvasive monitoring of the critically ill and avoids the morbidity and mortality that is associated with more invasive methods of patient monitoring. In addition, transesophageal echocardiography affords the practitioner reliable cardiac filling volumes based on direct left ventricular assessment compared to pressure data that are based on indirect right ventricular and pulmonary occlusive pressures. In a healthcare environment that seeks optimum patient assessment while requiring an approach that encourages cost-effective, noninvasive, and minimal patient risk, those nurse anesthetists who work in institutions that have transesophageal echocardiographic capabilities should learn this newer technology and begin to incorporate it into their practice.

Heart rate complexity: A novel approach to assessing cardiac stress reactivity.

PubMed

Brindle, Ryan C; Ginty, Annie T; Phillips, Anna C; Fisher, James P; McIntyre, David; Carroll, Douglas

2016-04-01

Correlation dimension (D2), a measure of heart rate (HR) complexity, has been shown to decrease in response to acute mental stress and relate to adverse cardiovascular health. However, the relationship between stress-induced changes in D2 and HR has yet to be established. The present studies aimed to assess this relationship systematically while controlling for changes in respiration and autonomic activity. In Study 1 (N = 25) D2 decreased during stress and predicted HR reactivity even after adjusting for changes in respiration rate, and cardiac vagal tone. This result was replicated in Study 2 (N = 162) and extended by including a measure of cardiac sympathetic activity; correlation dimension remained an independent predictor of HR reactivity in a hierarchical linear model containing measures of cardiac parasympathetic and sympathetic activity and their interaction. These results suggest that correlation dimension may provide additional information regarding cardiac stress reactivity above that provided by traditional measures of cardiac autonomic function. © 2015 Society for Psychophysiological Research.

Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease.

PubMed

Tanaka, Kayo; Tanaka, Hiroaki; Maki, Shintaro; Kubo, Michiko; Nii, Masafumi; Magawa, Shoichi; Hatano, Fumi; Tsuji, Makoto; Osato, Kazuhiro; Kamimoto, Yuki; Umekawa, Takashi; Ikeda, Tomoaki

2018-02-20

The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

Left atrial phasic function and heart rate variability in asymptomatic diabetic patients.

PubMed

Tadic, Marijana; Vukomanovic, Vladan; Cuspidi, Cesare; Suzic-Lazic, Jelena; Stanisavljevic, Dejana; Celic, Vera

2017-03-01

We evaluated left atrial (LA) phasic function and heart rate variability (HRV) in asymptomatic diabetic patients, and the relationship between HRV indices and LA phasic function assessed by volumes and speckle tracking imaging. This cross-sectional study included 55 asymptomatic patients with type 2 diabetes and 50 healthy controls without cardiovascular risk factors. All study subjects underwent laboratory analyses, complete two-dimensional echocardiography examination (2DE) and 24-h Holter monitoring. Maximum, minimum LA and pre-A LA volumes and volume indexes are significantly higher in diabetic patients. Total and passive LA emptying fractions (EF), representing the LA reservoir and conduit function, are significantly lower in diabetic subjects. Active LA EF, the parameter of the LA booster pump function, is compensatory increased in diabetic patients. Similar results were obtained by 2DE strain analysis. Cardiac autonomic function, assessed by HRV, is significantly deteriorated in diabetic patients. Time and frequency-domain HRV measures are significantly lower in diabetic subjects than in controls. HbA1c, LV mass index and HRV are associated with total LA EF and longitudinal LA strain independently of age, body mass index and LV diastolic function in the whole study population. LA phasic function and cardiac autonomic nervous system assessed by HRV are impacted by diabetes. HbA1c and HRV are independently associated with LA reservoir function evaluated by volumetric and strain methods in the whole study population. This study emphasizes the importance of determination of LA function and HRV as important markers of preclinical cardiac damage and autonomic function impairment in diabetic patients.

Multimodality imaging evaluation of Chagas disease: an expert consensus of Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI).

PubMed

Nunes, Maria Carmo P; Badano, Luigi Paolo; Marin-Neto, J Antonio; Edvardsen, Thor; Fernández-Golfín, Covadonga; Bucciarelli-Ducci, Chiara; Popescu, Bogdan A; Underwood, Richard; Habib, Gilbert; Zamorano, Jose Luis; Saraiva, Roberto Magalhães; Sabino, Ester Cerdeira; Botoni, Fernando A; Barbosa, Márcia Melo; Barros, Marcio Vinicius L; Falqueto, Eduardo; Simões, Marcus Vinicius; Schmidt, André; Rochitte, Carlos Eduardo; Rocha, Manoel Otávio Costa; Ribeiro, Antonio Luiz Pinho; Lancellotti, Patrizio

2018-04-01

To develop a document by Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI) to review and summarize the most recent evidences about the non-invasive assessment of patients with Chagas disease, with the intent to set up a framework for standardized cardiovascular imaging to assess cardiovascular morphologic and functional disturbances, as well as to guide the subsequent process of clinical decision-making. Chagas disease remains one of the most prevalent infectious diseases in Latin America, and has become a health problem in non-endemic countries. Dilated cardiomyopathy is the most severe manifestation of Chagas disease, which causes substantial disability and early mortality in the socially most productive population leading to a significant economical burden. Prompt and correct diagnosis of Chagas disease requires specialized clinical expertise to recognize the unique features of this disease. The appropriate and efficient use of cardiac imaging is pivotal for diagnosing the cardiac involvement in Chagas disease, to stage the disease, assess patients' prognosis and address management. Echocardiography is the most common imaging modality used to assess, and follow-up patients with Chagas disease. The presence of echocardiographic abnormalities is of utmost importance, since it allows to stage patients according to disease progression. In early stages of cardiac involvement, echocardiography may demonstrate segmental left ventricuar wall motion abnormalities, mainly in the basal segments of inferior, inferolateral walls, and the apex, which cannot be attributed to obstructive coronary artery arteries. The prevalence of segmental wall motion abnormalities varies according to the stage of the disease, reaching about 50% in patients with left ventricular dilatation and dysfunction. Speckle tracking echocardiography allows a more precise and quantitative measurement of the regional myocardial function. Since segmental wall motion abnormalities are frequent in Chagas disease, speckle tracking echocardiography may have an important clinical application in these patients, particularly in the indeterminate forms when abnormalities are more subtle. Speckle tracking echocardiography can also quantify the heterogeneity of systolic contraction, which is associated with the risk of arrhythmic events. Three-dimensional (3D) echocardiography is superior to conventional two-dimensional (2D) echocardiography for assessing more accurately the left ventricular apex and thus to detect apical aneurysms and thrombus in patients in whom ventricular foreshortening is suspected by 2D echocardiography. In addition, 3D echocardiography is more accurate than 2D Simpson s biplane rule for assessing left ventricular volumes and function in patients with significant wall motion abnormalities, including aneurysms with distorted ventricular geometry. Contrast echocardiography has the advantage to enhancement of left ventricular endocardial border, allowing for more accurate detection of ventricular aneurysms and thrombus in Chagas disease. Diastolic dysfunction is an important hallmark of Chagas disease even in its early phases. In general, left ventricular diastolic and systolic dysfunction coexist and isolated diastolic dysfunction is uncommon but may be present in patients with the indeterminate form. Right ventricular dysfunction may be detected early in the disease course, but in general, the clinical manifestations occur late at advanced stages of Chagas cardiomyopathy. Several echocardiographic parameters have been used to assess right ventricular function in Chagas disease, including qualitative evaluation, myocardial performance index, tissue Doppler imaging, tricuspid annular plane systolic excursion, and speckle tracking strain. Cardiac magnetic resonance (CMR) is useful to assess global and regional left ventricular function in patients with Chagas diseases. Myocardial fibrosis is a striking feature of Chagas cardiomyopathy and late gadolinium enhancement (LGE) is used to detect and quantify the extension of myocardial fibrosis. Myocardial fibrosis might have a role in risk stratification of patients with Chagas disease. Limited data are available regarding right ventricular function assessed by CMR in Chagas disease. Radionuclide ventriculography is used for global biventricular function assessment in patients with suspected or definite cardiac involvement in Chagas disease with suboptimal acoustic window and contraindication to CMR. Myocardial perfusion scintigraphy may improve risk stratification to define cardiac involvement in Chagas disease, especially in the patients with devices who cannot be submitted to CMR and in the clinical setting of Chagas patients whose main complaint is atypical chest pain. Detection of reversible ischemic defects predicts further deterioration of left ventricular systolic function and helps to avoid unnecessary cardiac catheterization and coronary angiography. Cardiac imaging is crucial to detect the cardiac involvement in patients with Chagas disease, stage the disease and stratify patient risk and address management. Unfortunately, most patients live in regions with limited access to imaging methods and point-of-care, simplified protocols, could improve the access of these remote populations to important information that could impact in the clinical management of the disease. Therefore, there are many fields for further research in cardiac imaging in Chagas disease. How to better provide an earlier diagnosis of cardiac involvement and improve patients risk stratification remains to be addressed using different images modalities.

Gender-related differences in β-adrenergic receptor-mediated cardiac remodeling.

PubMed

Zhu, Baoling; Liu, Kai; Yang, Chengzhi; Qiao, Yuhui; Li, Zijian

2016-12-01

Cardiac remodeling is the pathological basis of various cardiovascular diseases. In this study, we found gender-related differences in β-adrenergic receptor (AR)-mediated pathological cardiac remodeling. Cardiac remodeling model was established by subcutaneous injection of isoprenaline (ISO) for 14 days. Heart rate (HR), mean arterial pressure (MAP), and echocardiography were obtained on 7th and 14th days during ISO administration. Myocardial cross-sectional area and the ratio of heart mass to tibia length (HM/TL) were detected to assess cardiac hypertrophy. Picro-Sirius red staining (picric acid + Sirius red F3B) was used to evaluate cardiac fibrosis. Myocardial capillary density was assessed by immunohistochemistry for von Willebrand factor. Further, real-time PCR was used to measure the expression of β1-AR and β2-AR. Results showed that ISO induced cardiac remodeling, the extent of which was different between female and male mice. The extent of increase in cardiac wall thickness, myocardial cross-sectional area, and collagen deposition in females was less than that in males. However, no gender-related difference was observed in HR, MAP, cardiac function, and myocardial capillary density. The distinctive decrease of β2-AR expression, rather than a decrease of β1-AR expression, seemed to result in gender-related differences in cardiac remodeling.

Cardiac and pericardial tumors: A potential application of positron emission tomography-magnetic resonance imaging.

PubMed

Fathala, Ahmed; Abouzied, Mohei; AlSugair, Abdul-Aziz

2017-07-26

Cardiac and pericardial masses may be neoplastic, benign and malignant, non-neoplastic such as thrombus or simple pericardial cysts, or normal variants cardiac structure can also be a diagnostic challenge. Currently, there are several imaging modalities for diagnosis of cardiac masses; each technique has its inherent advantages and disadvantages. Echocardiography, is typically the initial test utilizes in such cases, Echocardiography is considered the test of choice for evaluation and detection of cardiac mass, it is widely available, portable, with no ionizing radiation and provides comprehensive evaluation of cardiac function and valves, however, echocardiography is not very helpful in many cases such as evaluation of extracardiac extension of mass, poor tissue characterization, and it is non diagnostic in some cases. Cross sectional imaging with cardiac computed tomography provides a three dimensional data set with excellent spatial resolution but utilizes ionizing radiation, intravenous iodinated contrast and relatively limited functional evaluation of the heart. Cardiac magnetic resonance imaging (CMR) has excellent contrast resolution that allows superior soft tissue characterization. CMR offers comprehensive evaluation of morphology, function, tissue characterization. The great benefits of CMR make CMR a highly useful tool in the assessment of cardiac masses. (Fluorine 18) fluorodeoxygluocse (FDG) positron emission tomography (PET) has become a corner stone in several oncological application such as tumor staging, restaging, treatment efficiency, FDG is a very useful imaging modality in evaluation of cardiac masses. A recent advance in the imaging technology has been the development of integrated PET-MRI system that utilizes the advantages of PET and MRI in a single examination. FDG PET-MRI provides complementary information on evaluation of cardiac masses. The purpose of this review is to provide several clinical scenarios on the incremental value of PET and MRI in the evaluation of cardiac masses.

Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction.

PubMed

Bender, Shawn B; DeMarco, Vincent G; Padilla, Jaume; Jenkins, Nathan T; Habibi, Javad; Garro, Mona; Pulakat, Lakshmi; Aroor, Annayya R; Jaffe, Iris Z; Sowers, James R

2015-05-01

Patients with obesity and diabetes mellitus exhibit a high prevalence of cardiac diastolic dysfunction (DD), an independent predictor of cardiovascular events for which no evidence-based treatment exists. In light of renin-angiotensin-aldosterone system activation in obesity and the cardioprotective action of mineralocorticoid receptor (MR) antagonists in systolic heart failure, we examined the hypothesis that MR blockade with a blood pressure-independent low-dose spironolactone (LSp) would treat obesity-associated DD in the Zucker obese (ZO) rat. Treatment of ZO rats exhibiting established DD with LSp normalized cardiac diastolic function, assessed by echocardiography. This was associated with reduced cardiac fibrosis, but not reduced hypertrophy, and restoration of endothelium-dependent vasodilation of isolated coronary arterioles via a nitric oxide-independent mechanism. Further mechanistic studies revealed that LSp reduced cardiac oxidative stress and improved endothelial insulin signaling, with no change in arteriolar stiffness. Infusion of Sprague-Dawley rats with the MR agonist aldosterone reproduced the DD noted in ZO rats. In addition, improved cardiac function in ZO-LSp rats was associated with attenuated systemic and adipose inflammation and an anti-inflammatory shift in cardiac immune cell mRNAs. Specifically, LSp increased cardiac markers of alternatively activated macrophages and regulatory T cells. ZO-LSp rats had unchanged blood pressure, serum potassium, systemic insulin sensitivity, or obesity-associated kidney injury, assessed by proteinuria. Taken together, these data demonstrate that MR antagonism effectively treats established obesity-related DD via blood pressure-independent mechanisms. These findings help identify a particular population with DD that might benefit from MR antagonist therapy, specifically patients with obesity and insulin resistance. © 2015 American Heart Association, Inc.

Effects of obstructive sleep apnea on hemodynamic parameters in patients entering cardiac rehabilitation.

PubMed

Hargens, Trent A; Aron, Adrian; Newsome, Laura J; Austin, Joseph L; Shafer, Brooke M

2015-01-01

Obstructive sleep apnea (OSA) is a prevalent form of sleep-disordered breathing. Evidence suggests that OSA may lead to cardiac remodeling, although the literature is equivocal. Previous literature suggests a high percentage of individuals entering a cardiac rehabilitation (CR) program also have OSA. The objective of this study was to determine whether resting hemodynamic variables were altered in OSA subjects entering CR compared with those without OSA, as determined by impedance cardiography. Subjects entering an early outpatient CR program were screened for OSA using an at-home screening device and verified by a sleep physician. Subjects were divided into an OSA group (n = 48) or a control group (n = 25) on the basis of the screening results. Hemodynamic variables were measured during supine rest using impedance cardiography. A 6-minute walk test was performed to assess functional capacity. The proportion of cardiac diagnoses was similar between groups. Overall, 66% of the subjects were positive for OSA. Subject groups did not differ by age, body mass index, heart rate, diastolic blood pressure, or functional capacity. Cardiac output, cardiac index, stroke volume, contractility index, and left cardiac work index were all significantly decreased in the OSA group compared with the control group (P < .05). Findings suggest that OSA results in decreased cardiac function in patients entering CR, likely because of pressure and volume changes associated with apneic events. This may place those individuals at a disadvantage in recovering from their cardiac event, and place them at increased risk for secondary complications.

Evaluation of platelet function in dogs with cardiac disease using the PFA-100 platelet function analyzer.

PubMed

Clancey, Noel; Burton, Shelley; Horney, Barbara; Mackenzie, Allan; Nicastro, Andrea; Côté, Etienne

2009-09-01

Cardiac disease has the potential to alter platelet function in dogs. Evaluation of platelet function using the PFA-100 analyzer in dogs of multiple breeds and with a broad range of cardiac conditions would help clarify the effect of cardiac disease on platelets. The objective of this study was to assess differences in closure time (CT) in dogs with cardiac disease associated with murmurs, when compared with that of healthy dogs. Thirty-nine dogs with cardiac murmurs and turbulent blood flow as determined echocardiographically were included in the study. The dogs represented 23 different breeds. Dogs with murmurs were further divided into those with atrioventricular valvular insufficiency (n=23) and subaortic stenosis (n=9). Fifty-eight clinically healthy dogs were used as controls. CTs were determined in duplicate on a PFA-100 analyzer using collagen/ADP cartridges. Compared with CTs in the control group (mean+/-SD, 57.6+/-5.9 seconds; median, 56.5 seconds; reference interval, 48.0-77.0 seconds), dogs with valvular insufficiency (mean+/-SD, 81.9+/-26.3 seconds; median, 78.0 seconds; range, 52.5-187 seconds), subaortic stenosis (71.4+/-16.5 seconds; median, 66.0 seconds; range, 51.5-95.0 seconds), and all dogs with murmurs combined (79.6+/-24.1 seconds; median, 74.0 seconds; range, 48.0-187 seconds) had significantly prolonged CTs (P<.01). The PFA-100 analyzer is useful in detecting platelet function defects in dogs with cardiac murmurs, most notably those caused by mitral and/or tricuspid valvular insufficiency or subaortic stenosis. The form of turbulent blood flow does not appear to be an important factor in platelet hypofunction in these forms of cardiac disease.

Intradialytic Cardiac Magnetic Resonance Imaging to Assess Cardiovascular Responses in a Short-Term Trial of Hemodiafiltration and Hemodialysis

PubMed Central

Buchanan, Charlotte; Mohammed, Azharuddin; Cox, Eleanor; Köhler, Katrin; Canaud, Bernard; Taal, Maarten W.; Selby, Nicholas M.; Francis, Susan

2017-01-01

Hemodynamic stress during hemodialysis (HD) results in recurrent segmental ischemic injury (myocardial stunning) that drives cumulative cardiac damage. We performed a fully comprehensive study of the cardiovascular effect of dialysis sessions using intradialytic cardiac magnetic resonance imaging (MRI) to examine the comparative acute effects of standard HD versus hemodiafiltration (HDF) in stable patients. We randomly allocated 12 patients on HD (ages 32–72 years old) to either HD or HDF. Patients were stabilized on a modality for 2 weeks before undergoing serial cardiac MRI assessment during dialysis. Patients then crossed over to the other modality and were rescanned after 2 weeks. Cardiac MRI measurements included cardiac index, stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow, and myocardial perfusion. Patients had mean±SEM ultrafiltration rates of 3.8±2.9 ml/kg per hour during HD and 4.4±2.5 ml/kg per hour during HDF (P=0.29), and both modalities provided a similar degree of cooling. All measures of systolic contractile function fell during HD and HDF, with partial recovery after dialysis. All patients experienced some degree of segmental left ventricular dysfunction, with severity proportional to ultrafiltration rate and BP reduction. Myocardial perfusion decreased significantly during HD and HDF. Treatment modality did not influence any of the cardiovascular responses to dialysis. In conclusion, in this randomized, crossover study, there was no significant difference in the cardiovascular response to HDF or HD with cooled dialysate as assessed with intradialytic MRI. PMID:28122851

Cardiac-Specific IGF-1 Receptor Transgenic Expression Protects Against Cardiac Fibrosis and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy

PubMed Central

Huynh, Karina; McMullen, Julie R.; Julius, Tracey L.; Tan, Joon Win; Love, Jane E.; Cemerlang, Nelly; Kiriazis, Helen; Du, Xiao-Jun; Ritchie, Rebecca H.

2010-01-01

OBJECTIVE Compelling epidemiological and clinical evidence has identified a specific cardiomyopathy in diabetes, characterized by early diastolic dysfunction and adverse structural remodeling. Activation of the insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) promotes physiological cardiac growth and enhances contractile function. The aim of the present study was to examine whether cardiac-specific overexpression of IGF-1R prevents diabetes-induced myocardial remodeling and dysfunction associated with a murine model of diabetes. RESEARCH DESIGN AND METHODS Type 1 diabetes was induced in 7-week-old male IGF-1R transgenic mice using streptozotocin and followed for 8 weeks. Diastolic and systolic function was assessed using Doppler and M-mode echocardiography, respectively, in addition to cardiac catheterization. Cardiac fibrosis and cardiomyocyte width, heart weight index, gene expression, Akt activity, and IGF-1R protein content were also assessed. RESULTS Nontransgenic (Ntg) diabetic mice had reduced initial (E)-to-second (A) blood flow velocity ratio (E:A ratio) and prolonged deceleration times on Doppler echocardiography compared with nondiabetic counterparts, indicative markers of diastolic dysfunction. Diabetes also increased cardiomyocyte width, collagen deposition, and prohypertrophic and profibrotic gene expression compared with Ntg nondiabetic littermates. Overexpression of the IGF-1R transgene markedly reduced collagen deposition, accompanied by a reduction in the incidence of diastolic dysfunction. Akt phosphorylation was elevated ∼15-fold in IGF-1R nondiabetic mice compared with Ntg, and this was maintained in a setting of diabetes. CONCLUSIONS The current study suggests that cardiac overexpression of IGF-1R prevented diabetes-induced cardiac fibrosis and diastolic dysfunction. Targeting IGF-1R–Akt signaling may represent a therapeutic target for the treatment of diabetic cardiac disease. PMID:20215428

Chronic Intermittent Hypobaric Hypoxia Improves Cardiac Function through Inhibition of Endoplasmic Reticulum Stress.

PubMed

Yuan, Fang; Zhang, Li; Li, Yan-Qing; Teng, Xu; Tian, Si-Yu; Wang, Xiao-Ran; Zhang, Yi

2017-08-11

We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis. CIHH treatment improved the recovery of left ventricular function and decreased cardiac infarct size and activity of LDH after I/R compared to control rats. Furthermore, CIHH treatment inhibited over-expression of ERS-related factors including GRP78, CHOP and caspase-12. CIHH-induced cardioprotection and inhibition of ERS were eliminated by application of dithiothreitol, an ERS inducer, and chelerythrine, a protein kinase C (PKC) inhibitor. In conclusion CIHH treatment exerts cardiac protection against I/R injury through inhibition of ERS via PKC signaling pathway.

Human auditory evoked potentials in the assessment of brain function during major cardiovascular surgery.

PubMed

Rodriguez, Rosendo A

2004-06-01

Focal neurologic and intellectual deficits or memory problems are relatively frequent after cardiac surgery. These complications have been associated with cerebral hypoperfusion, embolization, and inflammation that occur during or after surgery. Auditory evoked potentials, a neurophysiologic technique that evaluates the function of neural structures from the auditory nerve to the cortex, provide useful information about the functional status of the brain during major cardiovascular procedures. Skepticism regarding the presence of artifacts or difficulty in their interpretation has outweighed considerations of its potential utility and noninvasiveness. This paper reviews the evidence of their potential applications in several aspects of the management of cardiac surgery patients. The sensitivity of auditory evoked potentials to the effects of changes in brain temperature makes them useful for monitoring cerebral hypothermia and rewarming during cardiopulmonary bypass. The close relationship between evoked potential waveforms and specific anatomic structures facilitates the assessment of the functional integrity of the central nervous system in cardiac surgery patients. This feature may also be relevant in the management of critical patients under sedation and coma or in the evaluation of their prognosis during critical care. Their objectivity, reproducibility, and relative insensitivity to learning effects make auditory evoked potentials attractive for the cognitive assessment of cardiac surgery patients. From a clinical perspective, auditory evoked potentials represent an additional window for the study of underlying cerebral processes in healthy and diseased patients. From a research standpoint, this technology offers opportunities for a better understanding of the particular cerebral deficits associated with patients who are undergoing major cardiovascular procedures.

Bundled Postconditioning Therapies Improve Hemodynamics and Neurologic Recovery after 17 Minutes of Untreated Cardiac Arrest

PubMed Central

Bartos, Jason A.; Matsuura, Timothy R.; Sarraf, Mohammad; Youngquist, Scott T.; McKnite, Scott H.; Rees, Jennifer N.; Sloper, Daniel T.; Bates, Frank S.; Segal, Nicolas; Debaty, Guillaume; Lurie, Keith G.; Neumar, Robert W.; Metzger, Joseph M.; Riess, Matthias L.; Yannopoulos, Demetris

2014-01-01

Objective Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 minutes of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. Methods Following 17 minutes of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. Results Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 hours), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 hours). Conclusions Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 minutes of untreated cardiac arrest in pigs. PMID:25447036

Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia.

PubMed

Vaillant, Fanny; Lauzier, Benjamin; Ruiz, Matthieu; Shi, Yanfen; Lachance, Dominic; Rivard, Marie-Eve; Bolduc, Virginie; Thorin, Eric; Tardif, Jean-Claude; Des Rosiers, Christine

2016-10-01

While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker I f current, vs. β-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB +/+ ;LDLR -/- ). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13 C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. Copyright © 2016 the American Physiological Society.

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

PubMed Central

Babick, Andrea; Chapman, Donald; Zieroth, Shelley; Elimban, Vijayan; Dhalla, Naranjan S

2012-01-01

This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI-induced heart failure were associated with increases in plasma catecholamine levels. Haemodynamic examination revealed depressed cardiac function, whereas echocardiographic analysis showed impaired cardiac performance and marked increases in left ventricle wall thickness and chamber dilatation at 20 weeks of inducing MI. These changes in cardiac function, cardiac remodelling and plasma dopamine levels in heart failure were partially or fully reversed by losartan. Sarcoplasmic reticular (SR) Ca2+-pump activity and protein expression, protein and gene expression for phospholamban, as well as myofibrillar (MF) Ca2+-stimulated ATPase activity and α-myosin heavy chain mRNA levels were depressed, whereas β-myosin heavy chain expression was increased in failing hearts; these alterations were partially reversed by losartan. Although SR Ca2+-release activity and mRNA levels for SR Ca2+-pump were decreased in failing heart, these changes were not reversed upon losartan treatment; no changes in mRNA levels for SR Ca2+-release channels were observed in untreated or treated heart failure. These results suggest that the partial improvement of cardiac performance in heart failure due to MI by losartan treatment is associated with partial reversal of cardiac remodelling as well as partial recovery of SR and MF functions. PMID:22947202

Indonesian herbal medicine prevents hypertension-induced left ventricular hypertrophy by diminishing NADPH oxidase-dependent oxidative stress.

PubMed

Sulistyowati, Erna; Hsu, Jong-Hau; Cheng, Yuan-Bin; Chang, Fang-Rong; Chen, Ying-Fu; Yeh, Jwu-Lai

2017-10-17

Indonesian herbal medicine Centella asiatica , Justicia gendarussa and Imperata cylindrica decoction (CJID) are known to be efficacious for hypertension. Oxidative stress plays an important role in hypertension-induced left ventricular hypertrophy (H-LVH). This study evaluated whether CJID inhibit cardiac remodeling in spontaneously hypertensive rats (SHRs) through mechanism of oxidative stress-related cardiac-NADPH oxidase (NOXs) pathway: NOX1, NOX2 and NOX4. Forty-weeks-old SHRs and normotensive-WKY rats, were both randomly divided into 2 groups: CJID and control. All rats were treated for 5 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured. LV morphology, function and performance were assessed by histological staining and echocardiography. Serum and cardiac superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were assessed. Cardiac superoxide and hydrogen peroxide (H 2 O 2 ) productions, protein expressions of SOD2, SOD3, NOX1, NOX2 and NOX4 were also determined. We found that SBP and HR were significantly decreased in SHRs-treated group. Echocardiography showed that CJID significantly improved LV morphometry and function. CJID decreased MDA level, but increased SOD activity. Cardiac superoxide and H 2 O 2 generation were decreased in SHRs-treated group. CJID caused cardiac SODs expressions to be increased but NOXs expressions to be suppressed. In conclusion, CJID prevents H-LVH by reducing reactive oxygen species production via the NOXs-dependent pathway.

Indonesian herbal medicine prevents hypertension-induced left ventricular hypertrophy by diminishing NADPH oxidase-dependent oxidative stress

PubMed Central

Sulistyowati, Erna; Hsu, Jong-Hau; Cheng, Yuan-Bin; Chang, Fang-Rong; Chen, Ying-Fu; Yeh, Jwu-Lai

2017-01-01

Indonesian herbal medicine Centella asiatica, Justicia gendarussa and Imperata cylindrica decoction (CJID) are known to be efficacious for hypertension. Oxidative stress plays an important role in hypertension-induced left ventricular hypertrophy (H-LVH). This study evaluated whether CJID inhibit cardiac remodeling in spontaneously hypertensive rats (SHRs) through mechanism of oxidative stress-related cardiac-NADPH oxidase (NOXs) pathway: NOX1, NOX2 and NOX4. Forty-weeks-old SHRs and normotensive-WKY rats, were both randomly divided into 2 groups: CJID and control. All rats were treated for 5 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured. LV morphology, function and performance were assessed by histological staining and echocardiography. Serum and cardiac superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were assessed. Cardiac superoxide and hydrogen peroxide (H2O2) productions, protein expressions of SOD2, SOD3, NOX1, NOX2 and NOX4 were also determined. We found that SBP and HR were significantly decreased in SHRs-treated group. Echocardiography showed that CJID significantly improved LV morphometry and function. CJID decreased MDA level, but increased SOD activity. Cardiac superoxide and H2O2 generation were decreased in SHRs-treated group. CJID caused cardiac SODs expressions to be increased but NOXs expressions to be suppressed. In conclusion, CJID prevents H-LVH by reducing reactive oxygen species production via the NOXs-dependent pathway. PMID:29156835

Safety: the heart of the matter.

PubMed

Hayat, Sajad A; Senior, Roxy

2005-08-01

An integral part of evaluation of cardiac disease in modern day medicine is echocardiography. It has made great strides since the initial collaboration of Dr. Helmut Hertz and Dr. Inge Edler. In its modern day form, echocardiography maintains a legacy of a bedside utility while adopting many of the technologic advances ushered in by the digital era. As a result, it boasts a broad and growing spectrum of application including routine use in primary cardiac diagnosis and screening, therapeutic assessment, and guidance of interventional and surgical procedures. With the advent of ultrasound contrast agents it is now arguably the most complete 'one-stop' investigational tool to assess cardiac structure, function and perfusion. However, has it maintained its safety profile? The familiar and oft quoted dictum in medicine of "first do no harm" is of great importance for any diagnostic tool and patient safety should remain a primary consideration for any new investigational technique. In this issue Cosyns' et al. have examined whether some of the theoretical and in vitro experimental concerns surrounding myocardial injury during and following contrast echocardiography result in any detectable change in cardiac function.

Assessment of left ventricular myocardial deformation by cardiac MRI strain imaging reveals myocardial dysfunction in patients with primary cardiac tumors.

PubMed

Chen, Jing; Yang, Zhi-Gang; Xu, Hua-Yan; Shi, Ke; Guo, Ying-Kun

2018-02-15

To assess left ventricular myocardial deformation in patients with primary cardiac tumors. MRI was retrospectively performed in 61 patients, including 31 patients with primary cardiac tumors and 30 matched normal controls. Left ventricular strain and function parameters were then assessed by MRI-tissue tracking. Differences between the tumor group and controls, left and right heart tumor groups, left ventricular wall tumor and non-left ventricular wall tumor groups, and tumors with and without LV enlargement groups were assessed. Finally, the correlations among tumor diameter, myocardial strain, and LV function were analyzed. Left ventricular myocardial strain was milder for tumor group than for normal group. Peak circumferential strain (PCS) and its diastolic strain rate, longitudinal strains (PLS) and its diastolic strain rates, and peak radial systolic and diastolic velocities of the right heart tumor group were lower than those of the left heart tumor group (all p<0.050), but the peak radial systolic strain rate of the former was higher than that of the latter (p=0.017). The corresponding strains were lower in the left ventricular wall tumor groups than in the non-left ventricular wall tumor group (p<0.050). Peak radial systolic velocities were generally higher for tumors with LV enlargement than for tumors without LV enlargement (p<0.050). Peak radial strain, PCS, and PLS showed important correlations with the left ventricular ejection fraction (all p<0.050). MRI-tissue tracking is capable of quantitatively assessing left ventricular myocardial strain to reveal sub-clinical abnormalities of myocardial contractile function. Copyright © 2017 Elsevier B.V. All rights reserved.

An automatic method to calculate heart rate from zebrafish larval cardiac videos.

PubMed

Kang, Chia-Pin; Tu, Hung-Chi; Fu, Tzu-Fun; Wu, Jhe-Ming; Chu, Po-Hsun; Chang, Darby Tien-Hao

2018-05-09

Zebrafish is a widely used model organism for studying heart development and cardiac-related pathogenesis. With the ability of surviving without a functional circulation at larval stages, strong genetic similarity between zebrafish and mammals, prolific reproduction and optically transparent embryos, zebrafish is powerful in modeling mammalian cardiac physiology and pathology as well as in large-scale high throughput screening. However, an economical and convenient tool for rapid evaluation of fish cardiac function is still in need. There have been several image analysis methods to assess cardiac functions in zebrafish embryos/larvae, but they are still improvable to reduce manual intervention in the entire process. This work developed a fully automatic method to calculate heart rate, an important parameter to analyze cardiac function, from videos. It contains several filters to identify the heart region, to reduce video noise and to calculate heart rates. The proposed method was evaluated with 32 zebrafish larval cardiac videos that were recording at three-day post-fertilization. The heart rate measured by the proposed method was comparable to that determined by manual counting. The experimental results show that the proposed method does not lose accuracy while largely reducing the labor cost and uncertainty of manual counting. With the proposed method, researchers do not have to manually select a region of interest before analyzing videos. Moreover, filters designed to reduce video noise can alleviate background fluctuations during the video recording stage (e.g. shifting), which makes recorders generate usable videos easily and therefore reduce manual efforts while recording.

Cardiac CT for myocardial ischaemia detection and characterization--comparative analysis.

PubMed

Bucher, A M; De Cecco, C N; Schoepf, U J; Wang, R; Meinel, F G; Binukrishnan, S R; Spearman, J V; Vogl, T J; Ruzsics, B

2014-11-01

The assessment of patients presenting with symptoms of myocardial ischaemia remains one of the most common and challenging clinical scenarios faced by physicians. Current imaging modalities are capable of three-dimensional, functional and anatomical views of the heart and as such offer a unique contribution to understanding and managing the pathology involved. Evidence has accumulated that visual anatomical coronary evaluation does not adequately predict haemodynamic relevance and should be complemented by physiological evaluation, highlighting the importance of functional assessment. Technical advances in CT technology over the past decade have progressively moved cardiac CT imaging into the clinical workflow. In addition to anatomical evaluation, cardiac CT is capable of providing myocardial perfusion parameters. A variety of CT techniques can be used to assess the myocardial perfusion. The single energy first-pass CT and dual energy first-pass CT allow static assessment of myocardial blood pool. Dynamic cardiac CT imaging allows quantification of myocardial perfusion through time-resolved attenuation data. CT-based myocardial perfusion imaging (MPI) is showing promising diagnostic accuracy compared with the current reference modalities. The aim of this review is to present currently available myocardial perfusion techniques with a focus on CT imaging in light of recent clinical investigations. This article provides a comprehensive overview of currently available CT approaches of static and dynamic MPI and presents the results of corresponding clinical trials.

[A basis for application of cardiac contractility variability in the Evaluation and assessment of exercise and fitness].

PubMed

Bu, Bin; Wang, Aihua; Han, Haijun; Xiao, Shouzhong

2010-06-01

Cardiac contractility variability (CCV) is a new concept which is introduced in the research field of cardiac contractility in recent years, that is to say, there are some disparities between cardiac contractilities when heart contracts. The changing signals of cardiac contractility contain a plenty of information on the cardiovascular function and disorder. In order to collect and analyze the message, we could quantitatively evaluate the tonicity and equilibrium of cardiac sympathetic nerve and parasympathetic nerve, and the effects of bio-molecular mechanism on the cardiovascular activities. By analyzing CCV, we could further understand the background of human being's heritage characteristics, nerve types, the adjusting mechanism, the molecular biology, and the adjustment of cardiac automatic nerve. With the development of the computing techniques, the digital signal processing method and its application in medical field, this analysis has been progressing greatly. By now, the assessment of CCV, just like the analysis of heart rate variability, is mainly via time domain and frequency domain analysis. CCV is one of the latest research fields in human cardiac signals being scarcely reported in the field of sports medicine; however, its research progresses are of important value for cardiac physiology and pathology in sports medicine and rehabilitation medicine.

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

ACR-SPR-STR Practice Parameter for the Performance of Cardiac Positron Emission Tomography - Computed Tomography (PET/CT) Imaging.

PubMed

Subramaniam, Rathan M; Janowitz, Warren R; Johnson, Geoffrey B; Lodge, Martin A; Parisi, Marguerite T; Ferguson, Mark R; Hellinger, Jeffrey C; Gladish, Gregory W; Gupta, Narainder K

2017-12-01

This clinical practice parameter has been developed collaboratively by the American College of Radiology (ACR), the Society for Pediatric Radiology (SPR), and the Society of Thoracic Radiology (STR). This document is intended to act as a guide for physicians performing and interpreting positron emission tomography-computed tomography (PET/CT) of cardiac diseases in adults and children. The primary value of cardiac PET/CT imaging include evaluation of perfusion, function, viability, inflammation, anatomy, and risk stratification for cardiac-related events such as myocardial infarction and death. Optimum utility of cardiac PET/CT is achieved when images are interpreted in conjunction with clinical information and laboratory data. Measurement of myocardial blood flow, coronary flow reserve and detection of balanced ischemia are significant advantages of cardiac PET perfusion studies. Increasingly cardiac PET/CT is used in diagnosis and treatment response assessment for cardiac sarcoidosis.

An Optimized and Simplified System of Mouse Embryonic Stem Cell Cardiac Differentiation for the Assessment of Differentiation Modifiers

PubMed Central

Hartman, Matthew E.; Librande, Jason R.; Medvedev, Ivan O.; Ahmad, Rabiah N.; Moussavi-Harami, Farid; Gupta, Pritha P.; Chien, Wei-Ming; Chin, Michael T.

2014-01-01

Generating cardiomyocytes from embryonic stem cells is an important technique for understanding cardiovascular development, the origins of cardiovascular diseases and also for providing potential reagents for cardiac repair. Numerous methods have been published but often are technically challenging, complex, and are not easily adapted to assessment of specific gene contributions to cardiac myocyte differentiation. Here we report the development of an optimized protocol to induce the differentiation of mouse embryonic stem cells to cardiac myocytes that is simplified and easily adapted for genetic studies. Specifically, we made four critical findings that distinguish our protocol: 1) mouse embryonic stem cells cultured in media containing CHIR99021 and PD0325901 to maintain pluripotency will efficiently form embryoid bodies containing precardiac mesoderm when cultured in these factors at a reduced dosage, 2) low serum conditions promote cardiomyocyte differentiation and can be used in place of commercially prepared StemPro nutrient supplement, 3) the Wnt inhibitor Dkk-1 is dispensable for efficient cardiac differentiation and 4) tracking differentiation efficiency may be done with surface expression of PDGFRα alone. In addition, cardiac mesodermal precursors generated by this system can undergo lentiviral infection to manipulate the expression of specific target molecules to assess effects on cardiac myocyte differentiation and maturation. Using this approach, we assessed the effects of CHF1/Hey2 on cardiac myocyte differentiation, using both gain and loss of function. Overexpression of CHF1/Hey2 at the cardiac mesoderm stage had no apparent effect on cardiac differentiation, while knockdown of CHF1/Hey2 resulted in increased expression of atrial natriuretic factor and connexin 43, suggesting an alteration in the phenotype of the cardiomyocytes. In summary we have generated a detailed and simplified protocol for generating cardiomyocytes from mES cells that is optimized for investigating factors that affect cardiac differentiation. PMID:24667642

Incentive spirometry in major surgeries: a systematic review.

PubMed

Carvalho, Celso R F; Paisani, Denise M; Lunardi, Adriana C

2011-01-01

To conduct a systematic review to evaluate the evidence of the use of incentive spirometry (IS) for the prevention of postoperative pulmonary complications and for the recovery of pulmonary function in patients undergoing abdominal, cardiac and thoracic surgeries. Searches were performed in the following databases: Medline, Embase, Web of Science, PEDro and Scopus to select randomized controlled trials which the IS was used in pre- and/or post-operative in order to prevent postoperative pulmonary complications and/or recover lung function after abdominal, cardiac and thoracic surgery. Two reviewers independently assessed all studies. In addition, the studies quality was assessed using the PEDro scale. Thirty studies were included (14 abdominal, 13 cardiac and 3 thoracic surgery; n=3,370 patients). In the analysis of the methodological quality, studies achieved a PEDro average score of 5.6, 4.7 and 4.8 points in abdominal, cardiac and thoracic surgeries, respectively. Five studies (3 abdominal, 1 cardiac and 1 thoracic surgery) compared the effect of the IS with control group (no intervention) and no difference was detected in the evaluated outcomes. There was no evidence to support the use of incentive spirometry in the management of surgical patients. Despite this, the use of incentive spirometry remains widely used without standardization in clinical practice.

Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage

PubMed Central

Hadanny, A.; Golan, H.; Fishlev, G.; Bechor, Y.; Volkov, O.; Suzin, G.; Ben-Jacob, E.; Efrati, S.

2015-01-01

Abstract Purpose: Cognitive impairment may occur in 42–50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury. The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. Methods: Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. Results: The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5–7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. Conclusions: Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event. PMID:26409406

Self-reported physical activity and lung function two months after cardiac surgery--a prospective cohort study.

PubMed

Jonsson, Marcus; Urell, Charlotte; Emtner, Margareta; Westerdahl, Elisabeth

2014-03-28

Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health's national survey. Formal lung function testing was performed preoperatively and two months postoperatively. The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results.

Cardiac Light-Sheet Fluorescent Microscopy for Multi-Scale and Rapid Imaging of Architecture and Function

NASA Astrophysics Data System (ADS)

Fei, Peng; Lee, Juhyun; Packard, René R. Sevag; Sereti, Konstantina-Ioanna; Xu, Hao; Ma, Jianguo; Ding, Yichen; Kang, Hanul; Chen, Harrison; Sung, Kevin; Kulkarni, Rajan; Ardehali, Reza; Kuo, C.-C. Jay; Xu, Xiaolei; Ho, Chih-Ming; Hsiai, Tzung K.

2016-03-01

Light Sheet Fluorescence Microscopy (LSFM) enables multi-dimensional and multi-scale imaging via illuminating specimens with a separate thin sheet of laser. It allows rapid plane illumination for reduced photo-damage and superior axial resolution and contrast. We hereby demonstrate cardiac LSFM (c-LSFM) imaging to assess the functional architecture of zebrafish embryos with a retrospective cardiac synchronization algorithm for four-dimensional reconstruction (3-D space + time). By combining our approach with tissue clearing techniques, we reveal the entire cardiac structures and hypertrabeculation of adult zebrafish hearts in response to doxorubicin treatment. By integrating the resolution enhancement technique with c-LSFM to increase the resolving power under a large field-of-view, we demonstrate the use of low power objective to resolve the entire architecture of large-scale neonatal mouse hearts, revealing the helical orientation of individual myocardial fibers. Therefore, our c-LSFM imaging approach provides multi-scale visualization of architecture and function to drive cardiovascular research with translational implication in congenital heart diseases.

Short-term Exposure to Microgravity and the Associated Risk of Sudden Cardiac Arrest: Implications for Commercial Spaceflight

NASA Astrophysics Data System (ADS)

Laing, Kevin J. C.; Russamono, Thais

2013-02-01

The likelihood of trained astronauts developing a life threatening cardiac event during spaceflight is relatively rare, whilst the incidence in untrained individuals is unknown. Space tourists who live a sedentary lifestyle have reduced cardiovascular function, but the associated danger of sudden cardiac arrest (SCA) during a suborbital spaceflight (SOSF) is unclear. Risk during SOSF was examined by reviewing several microgravity studies and methods of determining poor cardiovascular condition. Accurately assessing cardiovascular function and improving baroreceptor sensitivity through exercise is suggested to reduce the incidence of SCA during future SOSFs. Future studies will benefit from past participants sharing medical history; allowing creation of risk profiles and suitable guidelines.

Non-invasive imaging of global and regional cardiac function in pulmonary hypertension

PubMed Central

Crowe, Tim; Jayasekera, Geeshath

2017-01-01

Pulmonary hypertension (PH) is a progressive illness characterized by elevated pulmonary artery pressure; however, the main cause of mortality in PH patients is right ventricular (RV) failure. Historically, improving the hemodynamics of pulmonary circulation was the focus of treatment; however, it is now evident that cardiac response to a given level of pulmonary hemodynamic overload is variable but plays an important role in the subsequent prognosis. Non-invasive tests of RV function to determine prognosis and response to treatment in patients with PH is essential. Although the right ventricle is the focus of attention, it is clear that cardiac interaction can cause left ventricular dysfunction, thus biventricular assessment is paramount. There is also focus on the atrial chambers in their contribution to cardiac function in PH. Furthermore, there is evidence of regional dysfunction of the two ventricles in PH, so it would be useful to understand both global and regional components of dysfunction. In order to understand global and regional cardiac function in PH, the most obvious non-invasive imaging techniques are echocardiography and cardiac magnetic resonance imaging (CMRI). Both techniques have their advantages and disadvantages. Echocardiography is widely available, relatively inexpensive, provides information regarding RV function, and can be used to estimate RV pressures. CMRI, although expensive and less accessible, is the gold standard of biventricular functional measurements. The advent of 3D echocardiography and techniques including strain analysis and stress echocardiography have improved the usefulness of echocardiography while new CMRI technology allows the measurement of strain and measuring cardiac function during stress including exercise. In this review, we have analyzed the advantages and disadvantages of the two techniques and discuss pre-existing and novel forms of analysis where echocardiography and CMRI can be used to examine atrial, ventricular, and interventricular function in patients with PH at rest and under stress. PMID:29064323

Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

PubMed

Al-Wakeel, Nadya; O h-Ici, Darach; Schmitt, Katharina R; Messroghli, Daniel R; Riesenkampff, Eugénie; Berger, Felix; Kuehne, Titus; Peters, Bjoern

2016-02-01

In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

Integrated approach to ischemic heart disease. The one-stop shop.

PubMed

Kramer, C M

1998-05-01

Magnetic resonance imaging is unique in its variety of applications for imaging the cardiovascular system. A thorough assessment of myocardial structure, function, and perfusion; assessment of coronary artery anatomy and flow; and spectroscopic evaluation of cardiac energetics can be readily performed by magnetic resonance imaging. One key to the advancement of cardiac magnetic resonance imaging as a clinical tool in the evaluation, the so called one stop shop. Improvements in magnetic resonance hardware, software, and imaging speed now permit this integrated examination. Cardiac magnetic resonance is a powerful technique with the potential to replace or complement other commonly used techniques in the diagnostic armamentarium of physicians caring for patients with ischemic heart disease.

Sulforaphane effects on postinfarction cardiac remodeling in rats: modulation of redox-sensitive prosurvival and proapoptotic proteins.

PubMed

Fernandes, Rafael Oliveira; De Castro, Alexandre Luz; Bonetto, Jéssica Hellen Poletto; Ortiz, Vanessa Duarte; Müller, Dalvana Daneliza; Campos-Carraro, Cristina; Barbosa, Silvia; Neves, Laura Tartari; Xavier, Léder Leal; Schenkel, Paulo Cavalheiro; Singal, Pawan; Khaper, Neelam; da Rosa Araujo, Alex Sander; Belló-Klein, Adriane

2016-08-01

This study investigated whether sulforaphane (SFN), a compound found in cruciferous vegetables, could attenuate the progression of post-myocardial infarction (MI) cardiac remodeling. Male Wistar rats (350 g) were allocated to four groups: SHAM (n=8), SHAM+SFN (n=7), MI (n=8) and MI+SFN (n=5). On the third day after surgery, cardiac function was assessed and SFN treatment (5 mg/kg/day) was started. At the end of 25 days of treatment, cardiac function was assessed and heart was collected to measure collagen content, oxidative stress and protein kinase. MI and MI+SFN groups presented cardiac dysfunction, without signs of congestion. Sulforaphane reduced fibrosis (2.1-fold) in infarcted rats, which was associated with a slight attenuation in the cardiac remodeling process. Both infarcted groups presented increases in the oxidative markers xanthine oxidase and 4-hydroxinonenal, as well as a parallel increase in the antioxidant enzymes glutathione peroxidase and superoxide dismutase. Moreover, sulforaphane stimulated the cytoprotective heme oxygenase-1 (HO-1) (38%). Oxidative markers correlated with ERK 1/2 activation. In the MI+SFN group, up-regulation of ERK 1/2 (34%) and Akt (35%), as well as down-regulation of p38 (52%), was observed. This change in the prosurvival kinase balance in the MI+SFN group was related to a down-regulation of apoptosis pathways (Bax/Bcl-2/caspase-3). Sulforaphane was unable to modulate autophagy. Taken together, sulforaphane increased HO-1, which may generate a redox environment in the cardiac tissue favorable to activation of prosurvival and deactivation of prodeath pathways. In conclusion, this natural compound contributes to attenuation of the fibrotic process, which may contribute to mitigation against the progression of cardiac remodeling postinfarction. Copyright © 2016 Elsevier Inc. All rights reserved.

Systolic and diastolic assessment by 3D-ASM segmentation of gated-SPECT Studies: a comparison with MRI

NASA Astrophysics Data System (ADS)

Tobon-Gomez, C.; Bijnens, B. H.; Huguet, M.; Sukno, F.; Moragas, G.; Frangi, A. F.

2009-02-01

Gated single photon emission tomography (gSPECT) is a well-established technique used routinely in clinical practice. It can be employed to evaluate global left ventricular (LV) function of a patient. The purpose of this study is to assess LV systolic and diastolic function from gSPECT datasets in comparison with cardiac magnetic resonance imaging (CMR) measurements. This is achieved by applying our recently implemented 3D active shape model (3D-ASM) segmentation approach for gSPECT studies. This methodology allows for generation of 3D LV meshes for all cardiac phases, providing volume time curves and filling rate curves. Both systolic and diastolic functional parameters can be derived from these curves for an assessment of patient condition even at early stages of LV dysfunction. Agreement of functional parameters, with respect to CMR measurements, were analyzed by means of Bland-Altman plots. The analysis included subjects presenting either LV hypertrophy, dilation or myocardial infarction.

Current Status of 3-Dimensional Speckle Tracking Echocardiography: A Review from Our Experiences

PubMed Central

Ishizu, Tomko; Aonuma, Kazutaka

2014-01-01

Cardiac function analysis is the main focus of echocardiography. Left ventricular ejection fraction (LVEF) has been the clinical standard, however, LVEF is not enough to investigate myocardial function. For the last decade, speckle tracking echocardiography (STE) has been the novel clinical tool for regional and global myocardial function analysis. However, 2-dimensional imaging methods have limitations in assessing 3-dimensional (3D) cardiac motion. In contrast, 3D echocardiography also has been widely used, in particular, to measure LV volume measurements and assess valvular diseases. Joining the technology bandwagon, 3D-STE was introduced in 2008. Experimental studies and clinical investigations revealed the reliability and feasibility of 3D-STE-derived data. In addition, 3D-STE provides a novel deformation parameter, area change ratio, which have the potential for more accurate assessment of overall and regional myocardial function. In this review, we introduced the features of the methodology, validation, and clinical application of 3D-STE based on our experiences for 7 years. PMID:25031794

Impact of the severity of end-stage liver disease in cardiac structure and function.

PubMed

Silvestre, Odilson Marcos; Bacal, Fernando; de Souza Ramos, Danusa; Andrade, Jose L; Furtado, Meive; Pugliese, Vincenzo; Belleti, Elisangela; Andraus, Wellington; Carrilho, Flair José; Carneiro D'Albuquerque, Luiz Augusto; Queiroz Farias, Alberto

2013-01-01

The impact of end-stage liver disease (ESLD) in cardiac remodeling of patients with cirrhosis is unknown. Our aim was to correlate the severity of ESLD with morphologic and functional heart changes. 184 patients underwent a protocol providing data on the severity of ESLD and undergoing echocardiography to assess the diameters of the left atrium and right ventricle; the systolic and diastolic diameters of the left ventricle, interventricular septum, and posterior wall of the left ventricle; systolic pulmonary artery pressure; ejection fraction; and diastolic function. Severity of ESLD was assessed by the Model for End-Stage Liver Disease (MELD) score. Left-atrial diameter (r = 0.323; IC 95% 0.190-0.455; p < 0.001), left-ventricular diastolic diameter (r = 0.177; IC 95% 0.033-0.320; p = 0.01) and systolic pulmonary artery pressure (r = 0.185; IC 95% 0.036-0.335; p = 0.02) significantly correlated with MELD score. Patients with MELD ≥ 16 had significantly higher left-atrial diameter and systolic pulmonary artery pressure, compared with patients with MELD scores < 16 points. Changes in cardiac structure and function correlate with the severity of ESLD.

Electrical and Mechanical Strategies to Enable Cardiac Repair and Regeneration

PubMed Central

Cao, Hung; Kang, Bong Jin; Lee, Chia-An; Shung, K. Kirk; Hsiai, Tzung K.

2015-01-01

Inadequate replacement of lost ventricular myocardium from myocardial infarction leads to heart failure. Investigating the regenerative capacity of mammalian hearts represents an emerging direction for tissue engineering and cell-based therapy. Recent advances in stem cells hold promise to restore cardiac functions. However, embryonic or induced pluripotent stem cell-derived cardiomyocytes lack functional phenotypes of the native myocardium, and transplanted tissues are not fully integrated for synchronized electrical and mechanical coupling with the host. In this context, this review highlights the mechanical and electrical strategies to promote cardiomyocyte maturation and integration, and to assess the functional phenotypes of regenerating myocardium. Simultaneous micro-electrocardiogram and high-frequency ultrasound techniques will also be introduced to assess electrical and mechanical coupling for small animal models of heart regeneration. PMID:25974948

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

PubMed

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

2015-01-19

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

Methods to assess Drosophila heart development, function and aging

PubMed Central

Ocorr, Karen; Vogler, Georg; Bodmer, Rolf

2014-01-01

In recent years the Drosophila heart has become an established model of many different aspects of human cardiac disease. This model has allowed identification of disease-causing mechanisms underlying congenital heart disease and cardiomyopathies and has permitted the study underlying genetic, metabolic and age-related contributions to heart function. In this review we discuss methods currently employed in the analysis of the Drosophila heart structure and function, such as optical methods to infer heart function and performance, electrophysiological and mechanical approaches to characterize cardiac tissue properties, and conclude with histological techniques used in the study of heart development and adult structure. PMID:24727147

Cardiac Impairment Evaluated by Transesophageal Echocardiography and Invasive Measurements in Rats Undergoing Sinoaortic Denervation

PubMed Central

Sirvente, Raquel A.; Irigoyen, Maria C.; Souza, Leandro E.; Mostarda, Cristiano; La Fuente, Raquel N.; Candido, Georgia O.; Souza, Pamella R. M.; Medeiros, Alessandra; Mady, Charles; Salemi, Vera M. C.

2014-01-01

Background Sympathetic hyperactivity may be related to left ventricular (LV) dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE) using intracardiac echocardiographic catheter. Methods and Results We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD). The rats (n = 32) were divided into 4 groups: 16 Wistar (W) with (n = 8) or without SAD (n = 8) and 16 spontaneously hypertensive rats (SHR) with (n = 8) or without SAD (SHRSAD) (n = 8). Blood pressure (BP) and heart rate (HR) did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV) concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV) pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. Conclusions Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease. PMID:24828834

Poor preoperative nutritional status is an important predictor of the retardation of rehabilitation after cardiac surgery in elderly cardiac patients.

PubMed

Ogawa, Masato; Izawa, Kazuhiro P; Satomi-Kobayashi, Seimi; Kitamura, Aki; Ono, Rei; Sakai, Yoshitada; Okita, Yutaka

2017-04-01

Preoperative nutritional status and physical function are important predictors of mortality and morbidity after cardiac surgery. However, the influence of nutritional status before cardiac surgery on physical function and the progress of postoperative rehabilitation requires clarification. To determine the effect of preoperative nutritional status on preoperative physical function and progress of rehabilitation after elective cardiac surgery. We enrolled 131 elderly patients with mean age of 73.7 ± 5.8 years undergoing cardiac surgery. We divided them into two groups by nutritional status as measured by the Geriatric Nutritional Risk Index (GNRI): high GNRI group (GNRI ≥ 92, n = 106) and low GNRI group (GNRI < 92, n = 25). Physical function was estimated by handgrip strength, knee extensor muscle strength (KEMS), the Short Physical Performance Battery (SPPB), and 6-minute walk test (6MWT). Progress of postoperative rehabilitation was evaluated by the number of days to independent walking after surgery, length of stay in the ICU, and length of hospital stay. After adjusting for potential confounding factors, preoperative handgrip strength (P = 0.034), KEMS (P = 0.009), SPPB (P < 0.0001), and 6MWT (P = 0.012) were all significantly better in the high GNRI group. Multiple regression analysis revealed that a low GNRI was an independent predictor of the retardation of postoperative rehabilitation. Preoperative nutritional status as assessed by the GNRI could reflect perioperative physical function. Preoperative poor nutritional status may be an independent predictor of the retardation of postoperative rehabilitation in patients undergoing elective cardiac surgery.

Perflurooctanoic Acid Induces Developmental Cardiotoxicity in ...

EPA Pesticide Factsheets

Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxisome proliferator activated receptor alpha (PPAR_). As the cardiovascular system is crucial for embryonic survival, PFOA-induced effects on the heart may partially explain embryonic mortality. To assess impacts of PFOA exposure on the developing heart in an avian model, we used histopathology and immunohistochemical staining for myosin to assess morphological alterations in 19-day-old chicken embryo hearts after PFOA exposure. Additionally, echocardiography and cardiac myofibril ATPase activity assays were used to assess functional alterations in 1-day-old hatchling chickens following developmental PFOA exposure. Overall thinning and thinning of a dense layer of myosin in the right ventricular wall were observed in PFOA-exposed chicken embryo hearts. Alteration of multiple cardiac structural and functional parameters, including left ventricular wall thickness, left ventricular volume, heart rate, stroke volume, and ejection fraction were detected with echocardiography in the exposed hatchling chickens. Assessment of ATPase activity indicated that the ratio of cardiac myofibril calcium-independent ATPase activity to calcium-dependent ATPase activity was not affected, which suggests that d

Influence of acid functionalization on the cardiopulmonary toxicity of carbon nanotubes and carbon black particles in mice

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

Tong Haiyan; McGee, John K.; Saxena, Rajiv K.

2009-09-15

Engineered carbon nanotubes are being developed for a wide range of industrial and medical applications. Because of their unique properties, nanotubes can impose potentially toxic effects, particularly if they have been modified to express functionally reactive chemical groups on their surface. The present study was designed to evaluate whether acid functionalization (AF) enhanced the cardiopulmonary toxicity of single-walled carbon nanotubes (SWCNT) as well as control carbon black particles. Mice were exposed by oropharyngeal aspiration to 10 or 40 {mu}g of saline-suspended single-walled carbon nanotubes (SWCNTs), acid-functionalized SWCNTs (AF-SWCNTs), ultrafine carbon black (UFCB), AF-UFCB, or 2 {mu}g LPS. 24 hours later,more » pulmonary inflammatory responses and cardiac effects were assessed by bronchoalveolar lavage and isolated cardiac perfusion respectively, and compared to saline or LPS-instilled animals. Additional mice were assessed for histological changes in lung and heart. Instillation of 40 {mu}g of AF-SWCNTs, UFCB and AF-UFCB increased percentage of pulmonary neutrophils. No significant effects were observed at the lower particle concentration. Sporadic clumps of particles from each treatment group were observed in the small airways and interstitial areas of the lungs according to particle dose. Patches of cellular infiltration and edema in both the small airways and in the interstitium were also observed in the high dose group. Isolated perfused hearts from mice exposed to 40 {mu}g of AF-SWCNTs had significantly lower cardiac functional recovery, greater infarct size, and higher coronary flow rate than other particle-exposed animals and controls, and also exhibited signs of focal cardiac myofiber degeneration. No particles were detected in heart tissue under light microscopy. This study indicates that while acid functionalization increases the pulmonary toxicity of both UFCB and SWCNTs, this treatment caused cardiac effects only with the AF-carbon nanotubes. Further experiments are needed to understand the physico-chemical processes involved in this phenomenon.« less

Clinicians' adherence to clinical practice guidelines for cardiac function monitoring during antipsychotic treatment: a retrospective report on 434 patients with severe mental illness.

PubMed

Manchia, Mirko; Firinu, Giorgio; Carpiniello, Bernardo; Pinna, Federica

2017-03-31

Severe mental illness (SMI) has considerable excess morbidity and mortality, a proportion of which is explained by cardiovascular diseases, caused in part by antipsychotic (AP) induced QT-related arrhythmias and sudden death by Torsade de Point (TdP). The implementation of evidence-based recommendations for cardiac function monitoring might reduce the incidence of these AP-related adverse events. To investigate clinicians' adherence to cardiac function monitoring before and after starting AP, we performed a retrospective assessment of 434 AP-treated SMI patients longitudinally followed-up for 5 years at an academic community mental health center. We classified antipsychotics according to their risk of inducing QT-related arrhythmias and TdP (Center for Research on Therapeutics, University of Arizona). We used univariate tests and multinomial or binary logistic regression model for data analysis. Univariate and multinomial regression analysis showed that psychiatrists were more likely to perform pre-treatment electrocardiogram (ECG) and electrolyte testing with AP carrying higher cardiovascular risk, but not on the basis of AP pharmacological class. Univariate and binomial regression analysis showed that cardiac function parameters (ECG and electrolyte balance) were more frequently monitored during treatment with second generation AP than with first generation AP. Our data show the presence of weaknesses in the cardiac function monitoring of AP-treated SMI patients, and might guide future interventions to tackle them.

Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery.

PubMed

Cordeiro, André Luiz Lisboa; de Melo, Thiago Araújo; Neves, Daniela; Luna, Julianne; Esquivel, Mateus Souza; Guimarães, André Raimundo França; Borges, Daniel Lago; Petto, Jefferson

2016-04-01

Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. 50 patients, 27 (54%) males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073) and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031). We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery.

Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury.

PubMed

West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V

2014-04-15

Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day(-1), 5 days week(-1) for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.

Use of milrinone to treat cardiac dysfunction in infants with pulmonary hypertension secondary to congenital diaphragmatic hernia: a review of six patients.

PubMed

Patel, Neil

2012-01-01

Pulmonary hypertension and secondary cardiac dysfunction are important contributors of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). Milrinone, a phosphodiesterase-3 inhibitor, may be useful in this setting for its combined actions as a pulmonary vasodilator and to improve systolic and diastolic function. This study aimed to assess the effects of milrinone on cardiac function and pulmonary artery pressure in infants with CDH. A retrospective review of echocardiograms performed on infants with CDH who received milrinone was performed. Tissue Doppler imaging velocities were used to assess systolic and diastolic function. Pulmonary artery pressure was assessed from the pattern and velocity of ductal shunting. Six infants with CDH and severe pulmonary hypertension were identified. Systolic and diastolic myocardial velocities were reduced in the right ventricle (RV) and interventricular septum (IVS) at baseline. In the 72 h after commencement of milrinone, there was a significant increase in early diastolic myocardial velocities in the RV, accompanied by increasing systolic velocities in the RV and IVS. Oxygenation index was significantly reduced, blood pressure unchanged, and ductal shunt velocity minimally altered over the same time period. Milrinone use was associated with an improvement in systolic and diastolic function in the RV, corresponding to an improvement in clinical status. Copyright © 2012 S. Karger AG, Basel.

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status.

PubMed

Léger, Thibault; Charrier, Alice; Moreau, Clarisse; Hininger-Favier, Isabelle; Mourmoura, Evangelia; Rigaudière, Jean-Paul; Pitois, Elodie; Bouvier, Damien; Sapin, Vincent; Pereira, Bruno; Azarnoush, Kasra; Demaison, Luc

2017-07-01

If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll-like receptor-9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF- α and IL-1 β In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham-operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF- α and gene expression of IL-1 β and TNF- α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF- α and IL-1 β on the cardiac function is known to occur at very high concentrations. The influence of low- to moderate-grade inflammation on the myocardial mechanical behavior must thus be revisited. © 2017 French National Institute of Agronomical Research (INRA). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Telmisartan regresses left ventricular hypertrophy in caveolin-1 deficient mice

PubMed Central

Kreiger, Marta H; Di Lorenzo, Annarita; Teutsch, Christine; Kauser, Katalin; Sessa, William C.

2011-01-01

The role of angiotensin II (Ang II) in promoting cardiac hypertrophy is well known, however the role of the Ang II in a spontaneous model of hypertrophy in mice lacking the protein caveolin-1 (Cav- KO) has not been explored. In this study, WT and Cav-1 KO mice were treated with angiotensin receptor blocker (ARB), telmisartan, and cardiac function assessed by echocardiography. Treatment of Cav-1 KO mice with telmisartan significantly improved cardiac function compared to age-matched, vehicle treated Cav-1 KO mice, while telmisartan did not affected cardiac function in WT mice. Both left ventricular (LV) weight to body weight ratios and LV to tibial length ratios were also reverted by telmisartan in Cav-1 KO but not WT mice. LV hypertrophy was associated with increased expression of natriuretic peptides-A and –B, β-myosin heavy chain and TGF-β and telmisartan treatment normalized the expression of these genes. Telmisartan reduced the expression of collagen genes (Col1A and Col3A) and associated perivascular fibrosis in intramyocardial vessels in Cav-1 KO mice. In conclusion, telmisartan treatment reduces indexes of cardiac hypertrophy in this unique genetic model of spontaneous LV hypertrophy. PMID:20585312

Real-time myocardium segmentation for the assessment of cardiac function variation

NASA Astrophysics Data System (ADS)

Zoehrer, Fabian; Huellebrand, Markus; Chitiboi, Teodora; Oechtering, Thekla; Sieren, Malte; Frahm, Jens; Hahn, Horst K.; Hennemuth, Anja

2017-03-01

Recent developments in MRI enable the acquisition of image sequences with high spatio-temporal resolution. Cardiac motion can be captured without gating and triggering. Image size and contrast relations differ from conventional cardiac MRI cine sequences requiring new adapted analysis methods. We suggest a novel segmentation approach utilizing contrast invariant polar scanning techniques. It has been tested with 20 datasets of arrhythmia patients. The results do not differ significantly more between automatic and manual segmentations than between observers. This indicates that the presented solution could enable clinical applications of real-time MRI for the examination of arrhythmic cardiac motion in the future.

Measuring Pressure Volume Loops in the Mouse.

PubMed

Townsend, DeWayne

2016-05-02

Understanding the causes and progression of heart disease presents a significant challenge to the biomedical community. The genetic flexibility of the mouse provides great potential to explore cardiac function at the molecular level. The mouse's small size does present some challenges in regards to performing detailed cardiac phenotyping. Miniaturization and other advancements in technology have made many methods of cardiac assessment possible in the mouse. Of these, the simultaneous collection of pressure and volume data provides a detailed picture of cardiac function that is not available through any other modality. Here a detailed procedure for the collection of pressure-volume loop data is described. Included is a discussion of the principles underlying the measurements and the potential sources of error. Anesthetic management and surgical approaches are discussed in great detail as they are both critical to obtaining high quality hemodynamic measurements. The principles of hemodynamic protocol development and relevant aspects of data analysis are also addressed.

Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

PubMed Central

Romond, Edward H.; Jeong, Jong-Hyeon; Rastogi, Priya; Swain, Sandra M.; Geyer, Charles E.; Ewer, Michael S.; Rathi, Vikas; Fehrenbacher, Louis; Brufsky, Adam; Azar, Catherine A.; Flynn, Patrick J.; Zapas, John L.; Polikoff, Jonathan; Gross, Howard M.; Biggs, David D.; Atkins, James N.; Tan-Chiu, Elizabeth; Zheng, Ping; Yothers, Greg; Mamounas, Eleftherios P.; Wolmark, Norman

2012-01-01

Purpose Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2–positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab. PMID:22987084

Knockout of p21-activated kinase-1 attenuates exercise-induced cardiac remodelling through altered calcineurin signalling

PubMed Central

Davis, Robert T.; Simon, Jillian N.; Utter, Megan; Mungai, Paul; Alvarez, Manuel G.; Chowdhury, Shamim A.K.; Heydemann, Ahlke; Ke, Yunbo; Wolska, Beata M.; Solaro, R. John

2015-01-01

Aims Despite its known cardiovascular benefits, the intracellular signalling mechanisms underlying physiological cardiac growth remain poorly understood. Therefore, the purpose of this study was to investigate a novel role of p21-activated kinase-1 (Pak1) in the regulation of exercise-induced cardiac hypertrophy. Methods and results Wild-type (WT) and Pak1 KO mice were subjected to 6 weeks of treadmill endurance exercise training (ex-training). Cardiac function was assessed via echocardiography, in situ haemodynamics, and the pCa–force relations in skinned fibre preparations at baseline and at the end of the training regimen. Post-translational modifications to the sarcomeric proteins and expression levels of calcium-regulating proteins were also assessed following ex-training. Heart weight/tibia length and echocardiography data revealed that there was marked hypertrophy following ex-training in the WT mice, which was not evident in the KO mice. Additionally, following ex-training, WT mice demonstrated an increase in cardiac contractility, myofilament calcium sensitivity, and phosphorylation of cardiac myosin-binding protein C, cardiac TnT, and tropomyosin compared with KO mice. With ex-training in WT mice, there were also increased protein levels of calcineurin and increased phosphorylation of phospholamban. Conclusions Our data suggest that Pak1 is essential for adaptive physiological cardiac remodelling and support previous evidence that demonstrates Pak1 signalling is important for cardiac growth and survival. PMID:26464331

Cardiac structure and function and dependency in the oldest old.

PubMed

Leibowitz, David; Jacobs, Jeremy M; Stessman-Lande, Irit; Cohen, Aharon; Gilon, Dan; Ein-Mor, Eliana; Stessman, Jochanan

2011-08-01

To examine the association between cardiac function and activities of daily living (ADLs) in an age-homogenous, community-dwelling population born in 1920 and 1921. Cross-sectional analysis of a prospective cohort study. Community-dwelling elderly population. Participants were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920 and 1921. Four hundred eighty-nine of the participants (228 male, 261 female) from the most recent set of data collection in 2005 and 2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. A home-based comprehensive assessment was performed to assess health and functional status, including performance of ADLs. Dependence was defined as needing assistance with one or more basic ADLs. Standard echocardiographic assessment of cardiac structure and function, including ejection fraction (EF) and diastolic function as assessed using early diastolic mitral annular tissue velocity measurements obtained using tissue Doppler, was performed. Of the participants with limitation in at least one ADL, significantly more had low EF (< 55%) than the group that was independent (52.6 % vs 39.1%; P=.01). In addition, participants with dependence in ADL had higher left ventricular mass index (LVMI) (129.3 vs 119.7 g/m²) and left atrial volume index (LAVI) (41.3 vs 36.7 mL/m²). There were no differences between the groups in percentage of participants with impaired diastolic function or average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (11.5 vs 11.8; P=.64). In this age-homogenous cohort of the oldest old, high LVMI and LAVI and indices of systolic but not diastolic function as assessed according to Doppler were associated with limitations in ADLs. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

Traction force microscopy of engineered cardiac tissues.

PubMed

Pasqualini, Francesco Silvio; Agarwal, Ashutosh; O'Connor, Blakely Bussie; Liu, Qihan; Sheehy, Sean P; Parker, Kevin Kit

2018-01-01

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.

Mammalian enabled (Mena) is a critical regulator of cardiac function

PubMed Central

Aguilar, Frédérick; Belmonte, Stephen L.; Ram, Rashmi; Noujaim, Sami F.; Dunaevsky, Olga; Protack, Tricia L.; Jalife, Jose; Todd Massey, H.; Gertler, Frank B.

2011-01-01

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena−/−) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena−/− mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena−/− hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena−/− mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction. PMID:21335464

Mammalian enabled (Mena) is a critical regulator of cardiac function.

PubMed

Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

2011-05-01

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

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

Kurhanewicz, Nicole

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once tomore » 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac effects. • Sensory irritation contributes to acrolein-induced cardiac arrhythmia & dysfunction.« less

Self-reported physical activity and lung function two months after cardiac surgery – a prospective cohort study

PubMed Central

2014-01-01

Background Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Methods Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health’s national survey. Formal lung function testing was performed preoperatively and two months postoperatively. Results The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). Conclusions An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results. PMID:24678691

c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

PubMed Central

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

2015-01-01

Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

Clinical use of cardiac PET/MRI: current state-of-the-art and potential future applications.

PubMed

Krumm, Patrick; Mangold, Stefanie; Gatidis, Sergios; Nikolaou, Konstantin; Nensa, Felix; Bamberg, Fabian; la Fougère, Christian

2018-05-01

Combined PET/MRI is a novel imaging method integrating the advances of functional and morphological MR imaging with PET applications that include assessment of myocardial viability, perfusion, metabolism of inflammatory tissue and tumors, as well as amyloid deposition imaging. As such, PET/MRI is a promising tool to detect and characterize ischemic and non-ischemic cardiomyopathies. To date, the greatest benefit may be expected for diagnostic evaluation of systemic diseases and cardiac masses that remain unclear in cardiac MRI, as well as for clinical and scientific studies in the setting of ischemic cardiomyopathies. Diagnosis and therapeutic monitoring of cardiac sarcoidosis has the potential of a possible 'killer-application' for combined cardiac PET/MRI. In this article, we review the current evidence and discuss current and potential future applications of cardiac PET/MRI.

Substrate- and isoform-specific proteome stability in normal and stressed cardiac mitochondria.

PubMed

Lau, Edward; Wang, Ding; Zhang, Jun; Yu, Hongxiu; Lam, Maggie P Y; Liang, Xiangbo; Zong, Nobel; Kim, Tae-Young; Ping, Peipei

2012-04-27

Mitochondrial protein homeostasis is an essential component of the functions and oxidative stress responses of the heart. To determine the specificity and efficiency of proteome turnover of the cardiac mitochondria by endogenous and exogenous proteolytic mechanisms. Proteolytic degradation of the murine cardiac mitochondria was assessed by 2-dimensional differential gel electrophoresis and liquid chromatography-tandem mass spectrometry. Mitochondrial proteases demonstrated a substrate preference for basic protein variants, which indicates a possible recognition mechanism based on protein modifications. Endogenous mitochondrial proteases and the cytosolic 20S proteasome exhibited different substrate specificities. The cardiac mitochondrial proteome contains low amounts of proteases and is remarkably stable in isolation. Oxidative damage lowers the proteolytic capacity of cardiac mitochondria and reduces substrate availability for mitochondrial proteases. The 20S proteasome preferentially degrades specific substrates in the mitochondria and may contribute to cardiac mitochondrial proteostasis.

Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling.

PubMed

Moro, Cécile; Jouan, Marie-Gabrielle; Rakotovao, Andry; Toufektsian, Marie-Claire; Ormezzano, Olivier; Nagy, Norbert; Tosaki, Arpad; de Leiris, Joël; Boucher, François

2007-11-01

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.

PET measurements of myocardial blood flow post myocardial infarction: Relationship to invasive and cardiac magnetic resonance studies and potential clinical applications.

PubMed

Gewirtz, Henry

2017-12-01

This review focuses on clinical studies concerning assessment of coronary microvascular and conduit vessel function primarily in the context of acute and sub acute myocardial infarction (MI). The ability of quantitative PET measurements of myocardial blood flow (MBF) to delineate underlying pathophysiology and assist in clinical decision making in this setting is discussed. Likewise, considered are physiological metrics fractional flow reserve, coronary flow reserve, index of microvascular resistance (FFR, CFR, IMR) obtained from invasive studies performed in the cardiac catheterization laboratory, typically at the time of PCI for MI. The role both of invasive studies and cardiac magnetic resonance (CMR) imaging in assessing microvascular function, a key determinant of prognosis, is reviewed. The interface between quantitative PET MBF measurements and underlying pathophysiology, as demonstrated both by invasive and CMR methodology, is discussed in the context of optimal interpretation of the quantitative PET MBF exam and its potential clinical applications.

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

PubMed

Badano, Luigi P; Miglioranza, Marcelo H; Edvardsen, Thor; Colafranceschi, Alexandre Siciliano; Muraru, Denisa; Bacal, Fernando; Nieman, Koen; Zoppellaro, Giacomo; Marcondes Braga, Fabiana G; Binder, Thomas; Habib, Gilbert; Lancellotti, Patrizio

2015-09-01

The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold-standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure.

PubMed

Lataro, Renata M; Silva, Carlos A A; Fazan, Rubens; Rossi, Marcos A; Prado, Cibele M; Godinho, Rosely O; Salgado, Helio C

2013-10-15

Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. The parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling, and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4 wk of pyridostigmine administration, per os, methylatropine and propranolol were used to evaluate the cardiac sympathovagal balance. The tachycardic response caused by methylatropine was considered to be the vagal tone, whereas the bradycardic response caused by propranolol was considered to be the sympathetic tone. In conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output, and contractility of the left ventricle. It was demonstrated that the long-term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.

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

PubMed

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

2016-12-20

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

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

PubMed Central

Lamoureux, Lorissa; Radhakrishnan, Jeejabai; Gazmuri, Raúl J.

2015-01-01

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the end-tidal CO2. A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes – but is not limited to – hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation. PMID:25938619

Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis.

PubMed

Perlini, Stefano; Salinaro, Francesco; Musca, Francesco; Mussinelli, Roberta; Boldrini, Michele; Raimondi, Ambra; Milani, Paolo; Foli, Andrea; Cappelli, Francesco; Perfetto, Federico; Palladini, Giovanni; Rapezzi, Claudio; Merlini, Giampaolo

2014-05-01

Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P <0.001), reduced end-diastolic left ventricular volumes (P <0.001), and diastolic dysfunction (P <0.001). In patients with preserved ejection fraction, mFS was markedly depressed [10.6% (8.7-13.5) vs. 17.8% (15.9-19.5) P <0.001]. At multivariable analysis, mFS, troponin I, and NT-pro-brain natriuretic peptide were the only significant prognostic determinants (P <0.001), whereas other indices of diastolic (E/E' ratio, transmitral and pulmonary vein flow velocities) and systolic function (tissue Doppler systolic indices, ejection fraction), or the presence/absence of congestive heart failure did not enter the model. In cardiac light-chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression.

PubMed

Kuhl, U; Lassner, D; Dorner, A; Rohde, M; Escher, F; Seeberg, B; Hertel, E; Tschope, C; Skurk, C; Gross, U M; Schultheiss, H-P; Poller, W

2013-09-01

Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.

Fibroblast growth factor 2 is an essential cardioprotective factor in a closed‐chest model of cardiac ischemia‐reperfusion injury

PubMed Central

House, Stacey L.; Wang, Joy; Castro, Angela M.; Weinheimer, Carla; Kovacs, Attila; Ornitz, David M.

2015-01-01

Abstract Fibroblast growth factor 2 (FGF2) is cardioprotective in in vivo models of myocardial infarction; however, whether FGF2 has a protective role in in vivo ischemia‐reperfusion (IR) injury, a model that more closely mimics acute myocardial infarction in humans, is not known. To assess the cardioprotective efficacy of endogenous FGF2, mice lacking a functional Fgf2 gene (Fgf2−/−) and wild‐type controls were subjected to closed‐chest regional cardiac IR injury (90 min ischemia, 7 days reperfusion). Fgf2−/− mice had significantly increased myocardial infarct size and significantly worsened cardiac function compared to wild‐type controls at both 1 and 7 days post‐IR injury. Pathophysiological analysis showed that at 1 day after IR injury Fgf2−/− mice have worsened cardiac strain patterns and increased myocardial cell death. Furthermore, at 7 days post‐IR injury, Fgf2−/− mice showed a significantly reduced cardiac hypertrophic response, decreased cardiac vessel density, and increased vessel diameter in the peri‐infarct area compared to wild‐type controls. These data reveal both acute cardioprotective and a longer term proangiogenic potential of endogenous FGF2 in a clinically relevant, in vivo, closed‐chest regional cardiac IR injury model that mimics acute myocardial infarction. PMID:25626875

Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

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

Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil

Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy.more » During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.« less

Live dynamic analysis of mouse embryonic cardiogenesis with functional optical coherence tomography

NASA Astrophysics Data System (ADS)

Lopez, Andrew L.; Wang, Shang; Larina, Irina V.

2018-02-01

Hemodynamic load, contractile forces, and tissue elasticity are regulators of cardiac development and contribute to the mechanical homeostasis of the developing vertebrate heart. Congenital heart disease (CHD) is a prevalent condition in the United States that affects 8 in 1000 live births[1], and has been linked to disrupted cardiac biomechanics[2-4]. Therefore, it is important to understand how these forces integrate and regulate vertebrate cardiac development to inform clinical strategies to treat CHD early on by reintroducing proper mechanical load or modulating downstream factors that rely on mechanical signalling. Toward investigation of biomechanical regulation of mammalian cardiovascular dynamics and development, our methodology combines live mouse embryo culture protocols, state-of-the-art structural and functional Optical Coherence Tomography (OCT), second harmonic generation (SHG) microscopy, and computational analysis. Using these approaches, we assess functional aspects of the developing heart and characterize how they coincide with a determinant of tissue stiffness and main constituent of the extracellular matrix (ECM)—type I collagen. This work is bringing us closer to understanding how cardiac biomechanics change temporally and spatially during normal development, and how it regulates ECM to maintain mechanical homeostasis for proper function.

Echocardiographic Assessment of Cardiac Function by Conventional and Speckle-Tracking Echocardiography in Dogs with Patent Ductus Arteriosus.

PubMed

Spalla, I; Locatelli, C; Zanaboni, A M; Brambilla, P; Bussadori, C

2016-05-01

Patent ductus arteriosus (PDA) is one of the most common congenital heart defects in dogs. Advanced echocardiographic techniques such as speckle-tracking echocardiography (STE) have not been extensively used to evaluate cardiac function in affected dogs. Advanced echocardiographic techniques are more sensitive than standard echocardiographic techniques in analyzing systolic function in dogs with PDA. Forty-four client-owned dogs: 34 dogs with PDA (preoperative evaluation) and 10 healthy sex- and weight-matched controls. Prospective study. Dogs were recruited over a 2-year period. Complete echocardiographic evaluation was performed, including conventional (end-diastolic volumes indexed to body surface area in B and M-mode [EDVIB /M ], end-systolic volumes indexed to body surface area in B and M-mode [ESVIB /M ], allometric scaling in diastole and systole [AlloD/S], pulmonary flow to systemic flow [Qp/Qs], ejection fraction [EF] and fractional shortening [FS]) and speckle-tracking echocardiography ([STE]: global longitudinal, radial and circumferential strain [S] and strain rate [SR]). Dogs with PDA had significantly different EDVIB /M , ESVIB /M , AlloD/S, Qp/Qs and all STE-derived parameters (global longitudinal S and SR, global circumferential S and SR, global radial S and SR)compared to healthy dogs. No correlation was found between standard techniques (EDVIB /M , ESVIB /M , AlloD/S, Qp/Qs) and STE-derived parameters (global longitudinal, circumferential and radial S and SR). Conventional parameters routinely used to assess systolic function (EF and FS) were not different between the groups; STE-derived parameters identified subtle changes in cardiac systolic function and contractility between the 2 groups of dogs. Based on these findings, STE may be a more appropriate tool to assess cardiac contractility in dogs with PDA. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Calculation of Cardiac Kinetic Energy Index from PET images.

PubMed

Sims, John; Oliveira, Marco Antônio; Meneghetti, José Claudio; Gutierrez, Marco Antônio

2015-01-01

Cardiac function can be assessed from displacement measurements in imaging modalities from nuclear medicine Using positron emission tomography (PET) image sequences with Rubidium-82, we propose and estimate the total Kinetic Energy Index (KEf) obtained from the velocity field, which was calculated using 3D optical flow(OF) methods applied over the temporal image sequence. However, it was found that the brightness of the image varied unexpectedly between frames, violating the constant brightness assumption of the OF method and causing large errors in estimating the velocity field. Therefore total brightness was equalized across image frames and the adjusted configuration tested with rest perfusion images acquired from individuals with normal (n=30) and low (n=33) cardiac function. For these images KEf was calculated as 0.5731±0.0899 and 0.3812±0.1146 for individuals with normal and low cardiac function respectively. The ability of KEf to properly classify patients into the two groups was tested with a ROC analysis, with area under the curve estimated as 0.906. To our knowledge this is the first time that KEf has been applied to PET images.

Influencing factors of NT-proBNP level inheart failure patients with different cardiacfunctions and correlation with prognosis.

PubMed

Xu, Liang; Chen, Yanchun; Ji, Yanni; Yang, Song

2018-06-01

Factors influencing N-terminal pro-brain natriuretic peptide (NT-proBNP) level in heart failure patients with different cardiac functions were identified to explore the correlations with prognosis. Eighty heart failure patients with different cardiac functions treated in Yixing People's Hospital from January 2016 to June 2017 were selected, and divided into two groups (group with cardiac function in class II and below and group with cardiac function in class III and above), according to the cardiac function classification established by New York Heart Association (NYHA). Blood biochemical test and outcome analysis were conducted to measure serum NT-proBNP and matrix metalloproteinase-9 (MMP-9) levels in patients with different cardiac functions, and correlations between levels of NT-proBNP and MMP-9 and left ventricular ejection fraction (LVEF) level were analyzed in patients with different cardiac functions at the same time. In addition, risk factors for heart failure in patients with different cardiac functions were analyzed. Compared with the group with cardiac function in class III and above, the group with cardiac function in class II and below had significantly lower serum NT-proBNP and MMP-9 levels (p<0.05). For echocardiogram indexes, left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) in the group with cardiac function in class II and below were obviously lower than those in the group with cardiac function in class III and above (p<0.05), while LVEF was higher in group with cardiac function in class II and below than that in group with cardiac function in class III and above (p<0.05). NT-proBNP and MMP-9 levels were negatively correlated with LVEF level [r=-0.8517 and -0.8517, respectively, p<0.001 (<0.05)]. Cardiac function in class III and above, increased NT-proBNP, increased MMP-9 and decreased LVEF were relevant risk factors and independent risk factors for heart failure in patients with different cardiac functions. NT-proBNP and MMP-9 levels are negatively correlated with LVEF in patients regardless of the cardiac function class. Therefore, attention should be paid to patients who have cardiac function in class III and above, increased NT-proBNP and MMP-9 levels and decreased LVEF in clinical practices, so as to actively prevent and treat heart failure.

Injection of Peptide nanogels preserves postinfarct diastolic function and prolongs efficacy of cell therapy in pigs.

PubMed

Lin, Yi-Dong; Chang, Ming-Yao; Cheng, Bill; Liu, Yen-Wen; Lin, Lung-Chun; Chen, Jyh-Hong; Hsieh, Patrick C H

2015-05-01

Accumulating evidence suggests that the benefits of cell therapy for cardiac repair are modest and transient due to progressive harmful cardiac remodeling as well as loss of transplanted cells. We previously demonstrated that injection of peptide nanofibers (NFs) reduces ventricular remodeling and facilitates cell retention at 1 month after acute myocardial infarction (MI) in pigs. However, it remains unclear whether these benefits still persist as the material is being degraded. In this study, 2 mL of placebo or NFs, with or without 1×10(8) mononuclear cells (MNCs), was injected into the pig myocardium after MI (n≥5 in each group), and cardiac function was assessed by echocardiography, including myocardial deformation analyses and catheterization at 3 months post-MI. Our results reveal that MNC-only injection slightly improved cardiac systolic function at 1 month post-MI, but this benefit was lost at later time points (ejection fraction: 42.0±2.3 in MI+normal saline [NS] and 43.5±1.1 in MI+MNCs). In contrast, NF-only injection resulted in improved cardiac diastolic function and reduced pathological remodeling at 3 months post-MI. Furthermore, combined injection of MNCs/NFs provided a greater and longer term cardiac performance (52.1±1.2 in MI+MNCs/NFs, p<0.001 versus MI+NS and MI+MNCs) and 11.3-fold transplanted cell retention. We also found that about 30% NFs remained at 3 months after injection; however, endogenous myofibroblasts were recruited to the NF-injected microenvironment to replace the degraded NFs and preserved cardiac dimensions and mechanics. In conclusion, we demonstrated that injection of NFs contributes to preservation of ventricular mechanical integrity and sustains MNC efficacy at 3 months postinjection.

Does point-of-care functional echocardiography enhance cardiovascular care in the NICU?

PubMed

Sehgal, A; McNamara, P J

2008-11-01

Although the last two decades have seen major advances in the care of sick, extremely premature newborns, the approach to cardiovascular assessment and monitoring remains suboptimal owing to an overreliance on poorly predictive clinical markers such as heart rate or capillary refill time. Point-of-care functional echocardiography (PCFecho) enables real-time evaluation of cardiac performance and systemic hemodynamics to characterize acute physiology, identify the exact nature of cardiovascular compromise and guide therapeutic decisions. In this article, we will review four clinical scenarios where bedside functional cardiac imaging enabled delineation of the real clinical problem and refinement of the therapeutic care plan with direct patient benefits.

Echocardiography in the Era of Multimodality Cardiovascular Imaging

PubMed Central

Shah, Benoy Nalin

2013-01-01

Echocardiography remains the most frequently performed cardiac imaging investigation and is an invaluable tool for detailed and accurate evaluation of cardiac structure and function. Echocardiography, nuclear cardiology, cardiac magnetic resonance imaging, and cardiovascular-computed tomography comprise the subspeciality of cardiovascular imaging, and these techniques are often used together for a multimodality, comprehensive assessment of a number of cardiac diseases. This paper provides the general cardiologist and physician with an overview of state-of-the-art modern echocardiography, summarising established indications as well as highlighting advances in stress echocardiography, three-dimensional echocardiography, deformation imaging, and contrast echocardiography. Strengths and limitations of echocardiography are discussed as well as the growing role of real-time three-dimensional echocardiography in the guidance of structural heart interventions in the cardiac catheter laboratory. PMID:23878804

[Cardiovascular assessment and management before non-cardiac surgery].

PubMed

Schwarz, Stefanie; Bernheim, Alain M

2015-05-06

The preoperative cardiovascular risk management accounts for patient-related risk factors, the circumstances leading to the surgical procedure, and the risk of the operation. While urgent operations should not be delayed for cardiac testing, an elective surgical intervention should be postponed in unstable cardiac conditions. In stable cardiac situations, prophylactic coronary interventions to reduce the risk of perioperative complications are rarely indicated. Therefore, in most cases, the planned operation can be performed without previous cardiac stress testing or coronary angiography. Preoperative imaging stress testing is recommended for patients with poor functional capacities that are at high cardiovascular risk prior to a high-risk operation. According to the literature, preoperative prophylactic administration of betablockers and aspirin is controversial. Preoperative discontinuation of dual anti-platelet therapy within six months following drug-eluting stent implantation is not recommended.

Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β-adrenergic system and does not compromise cardiac function.

PubMed

Vileigas, Danielle F; de Deus, Adriana F; da Silva, Danielle C T; de Tomasi, Loreta C; de Campos, Dijon H S; Adorni, Caroline S; de Oliveira, Scarlet M; Sant'Ana, Paula G; Okoshi, Katashi; Padovani, Carlos R; Cicogna, Antonio C

2016-09-01

Obesity is a worldwide pandemic associated with high incidence of cardiovascular disease. The mechanisms by which the obesity leads cardiac dysfunction are not fully elucidated and few studies have evaluated the relationship between obesity and proteins involved in myocardial β-adrenergic (βA) system. The purpose of this study was to evaluate the cardiac function and βA pathway components in myocardium of obese rats. Male Wistar rats were distributed into two groups: control (n = 17; standard diet) and obese (n = 17; saturated high-fat diet) fed for 33 weeks. Nutritional profile and comorbidities were assessed. Cardiac structure and function was evaluated by macroscopic postmortem, echocardiographic and isolated papillary muscle analyzes. Myocardial protein expression of β1- and β2-adrenergic receptors, Gαs protein, adenylate cyclase (AC) and protein kinase A (PKA) was performed by Western blot. Cardiac cyclic adenosine monophosphate (cAMP) levels and PKA activity were assessed by ELISA Obese rats showed increased adiposity index (P < 0.001) and several comorbidities as hypertension, glucose intolerance, insulin resistance, and dyslipidemia compared with control rats. Echocardiographic assessment revealed increased left atrium diameter (C: 4.98 ± 0.38 vs. Ob: 5.47 ± 0.53, P = 0.024) and posterior wall shortening velocity (C: 37.1 ± 3.6 vs. Ob: 41.8 ± 3.8, P = 0.007) in obese group. Papillary muscle evaluation indicated that baseline data and myocardial responsiveness to isoproterenol stimulation were similar between the groups. Protein expression of myocardial AC was higher in obese group than in the control (C: 1.00 ± 0.21 vs. Ob: 1.25 ± 0.10, P = 0.025), whereas the other components were unchanged. These results suggest that saturated high-fat diet-induced obesity was not effective in triggering cardiac dysfunction and impair the beta-adrenergic signaling. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Assessment of left ventricular function using pulsed tissue Doppler imaging in healthy dogs and dogs with spontaneous mitral regurgitation.

PubMed

Teshima, Kenji; Asano, Kazushi; Sasaki, Yukie; Kato, Yuka; Kutara, Kenji; Edamura, Kazuya; Hasegawa, Atsuhiko; Tanaka, Shigeo

2005-12-01

Pulsed tissue Doppler imaging (pulsed TDI) has been demonstrated to be useful for the estimation of left ventricular (LV) systolic and diastolic functions in various human cardiac diseases. The objectives of this study were to investigate the relationship between pulsed TDI and LV function by using cardiac catheterization in healthy dogs and to evaluate the clinical usefulness of pulsed TDI in dogs with spontaneous mitral regurgitation (MR). The peak early diastolic velocity (E'), peak atrial systolic velocity (A'), and peak systolic velocity (S') were detectable in the velocity profiles of the mitral annulus in all the dogs. In the healthy dogs, S' and E' were correlated with LV peak +dP/dt and -dP/dt, respectively. E' was lower in dogs with MR than in dogs without cardiac diseases. E/E' in the MR dogs with decompensated heart failure was significantly increased in comparison with those with compensated heart failure. The sensitivity and specificity of the E/E' cutoff value of 13.0 for identifying decompensated heart failure were 80% and 83%, respectively. In addition, E/E' was significantly correlated with the ratio of left atrial to aortic diameter. These findings suggest that canine pulsed TDI can be applied clinically for estimation of cardiac function and detection of cardiac decompensation and left atrial volume overload in dogs with MR.

Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction

PubMed Central

Russell, Richard O.; Rackley, Charles E.; Pombo, Jaoquin; Hunt, David; Potanin, Constantine; Dodge, Harold T.

1970-01-01

Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function. Images PMID:5431663

Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography

PubMed Central

Boppart, Stephen A.; Tearney, Gary J.; Bouma, Brett E.; Southern, James F.; Brezinski, Mark E.; Fujimoto, James G.

1997-01-01

Studies investigating normal and abnormal cardiac development are frequently limited by an inability to assess cardiovascular function within the intact organism. In this work, optical coherence tomography (OCT), a new method of micron-scale, noninvasive imaging based on the measurement of backscattered infrared light, was introduced for the high resolution assessment of structure and function in the developing Xenopus laevis cardiovascular system. Microstructural details, such as ventricular size and wall positions, were delineated with OCT at 16-μm resolution and correlated with histology. Three-dimensional representation of the cardiovascular system also was achieved by repeated cross-sectional imaging at intervals of 25 μm. In addition to structural information, OCT provides high speed in vivo axial ranging and imaging, allowing quantitative dynamic activity, such as ventricular ejection fraction, to be assessed. The sensitivity of OCT for dynamic assessment was demonstrated with an inotropic agent that altered cardiac function and dimensions. Optical coherence tomography is an attractive new technology for assessing cardiovascular development because of its high resolution, its ability to image through nontransparent structures, and its inexpensive portable design. In vivo and in vitro imaging are performed at a resolution approaching that of histopathology without the need for animal killing. PMID:9113976

Functional cardiac magnetic resonance microscopy

NASA Astrophysics Data System (ADS)

Brau, Anja Christina Sophie

2003-07-01

The study of small animal models of human cardiovascular disease is critical to our understanding of the origin, progression, and treatment of this pervasive disease. Complete analysis of disease pathophysiology in these animal models requires measuring structural and functional changes at the level of the whole heart---a task for which an appropriate non-invasive imaging method is needed. The purpose of this work was thus to develop an imaging technique to support in vivo characterization of cardiac structure and function in rat and mouse models of cardiovascular disease. Whereas clinical cardiac magnetic resonance imaging (MRI) provides accurate assessment of the human heart, the extension of cardiac MRI from humans to rodents presents several formidable scaling challenges. Acquiring images of the mouse heart with organ definition and fluidity of contraction comparable to that achieved in humans requires an increase in spatial resolution by a factor of 3000 and an increase in temporal resolution by a factor of ten. No single technical innovation can meet the demanding imaging requirements imposed by the small animal. A functional cardiac magnetic resonance microscopy technique was developed by integrating improvements in physiological control, imaging hardware, biological synchronization of imaging, and pulse sequence design to achieve high-quality images of the murine heart with high spatial and temporal resolution. The specific methods and results from three different sets of imaging experiments are presented: (1) 2D functional imaging in the rat with spatial resolution of 175 mum2 x 1 mm and temporal resolution of 10 ms; (2) 3D functional imaging in the rat with spatial resolution of 100 mum 2 x 500 mum and temporal resolution of 30 ms; and (3) 2D functional imaging in the mouse with spatial resolution down to 100 mum2 x 1 mm and temporal resolution of 10 ms. The cardiac microscopy technique presented here represents a novel collection of technologies capable of acquiring routine high-quality images of murine cardiac structure and function with minimal artifacts and markedly higher spatial resolution compared to conventional techniques. This work is poised to serve a valuable role in the evaluation of cardiovascular disease and should find broad application in studies ranging from basic pathophysiology to drug discovery.

Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

PubMed

Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

2016-05-01

Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

Role of Copper and Homocysteine in Pressure Overload Heart Failure

PubMed Central

Hughes, William M.; Rodriguez, Walter E.; Rosenberger, Dorothea; Chen, Jing; Sen, Utpal; Tyagi, Neetu; Moshal, Karni S.; Vacek, Thomas; Kang, Y. James

2009-01-01

Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart. PMID:18679830

Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation

PubMed Central

Bernardo, Bianca C.; Sapra, Geeta; Patterson, Natalie L.; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A.; McMullen, Julie R.

2015-01-01

Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions. PMID:26660322

Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

PubMed

Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

2015-01-01

Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

Cardiac Magnetic Resonance Imaging in Ischemic Heart Disease

PubMed Central

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

2011-01-01

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

Can a Home-based Cardiac Physical Activity Program Improve the Physical Function Quality of Life in Children with Fontan Circulation?

PubMed

Jacobsen, Roni M; Ginde, Salil; Mussatto, Kathleen; Neubauer, Jennifer; Earing, Michael; Danduran, Michael

2016-01-01

Patients after Fontan operation for complex congenital heart disease (CHD) have decreased exercise capacity and report reduced health-related quality of life (HRQOL). Studies suggest hospital-based cardiac physical activity programs can improve HRQOL and exercise capacity in patients with CHD; however, these programs have variable adherence rates. The impact of a home-based cardiac physical activity program in Fontan survivors is unclear. This pilot study evaluated the safety, feasibility, and benefits of an innovative home-based physical activity program on HRQOL in Fontan patients. A total of 14 children, 8-12 years, with Fontan circulation enrolled in a 12-week moderate/high intensity home-based cardiac physical activity program, which included a home exercise routine and 3 formalized in-person exercise sessions at 0, 6, and 12 weeks. Subjects and parents completed validated questionnaires to assess HRQOL. The Shuttle Test Run was used to measure exercise capacity. A Fitbit Flex Activity Monitor was used to assess adherence to the home activity program. Of the 14 patients, 57% were male and 36% had a dominant left ventricle. Overall, 93% completed the program. There were no adverse events. Parents reported significant improvement in their child's overall HRQOL (P < .01), physical function (P < .01), school function (P = .01), and psychosocial function (P < .01). Patients reported no improvement in HRQOL. Exercise capacity, measured by total shuttles and exercise time in the Shuttle Test Run and calculated VO2 max, improved progressively from baseline to the 6 and 12 week follow up sessions. Monthly Fitbit data suggested adherence to the program. This 12-week home-based cardiac physical activity program is safe and feasible in preteen Fontan patients. Parent proxy-reported HRQOL and objective measures of exercise capacity significantly improved. A 6-month follow up session is scheduled to assess sustainability. A larger study is needed to determine the applicability and reproducibility of these findings in other age groups and forms of complex CHD. © 2016 Wiley Periodicals, Inc.

The use of the virtual reality as intervention tool in the postoperative of cardiac surgery.

PubMed

Cacau, Lucas de Assis Pereira; Oliveira, Géssica Uruga; Maynard, Luana Godinho; Araújo Filho, Amaro Afrânio de; Silva, Walderi Monteiro da; Cerqueria Neto, Manoel Luiz; Antoniolli, Angelo Roberto; Santana-Filho, Valter J

2013-06-01

Cardiac surgery has been the intervention of choice in many cases of cardiovascular diseases. Susceptibility to postoperative complications, cardiac rehabilitation is indicated. Therapeutic resources, such as virtual reality has been helping the rehabilitational process. The aim of the study was to evaluate the use of virtual reality in the functional rehabilitation of patients in the postoperative period. Patients were randomized into two groups, Virtual Reality (VRG, n = 30) and Control (CG, n = 30). The response to treatment was assessed through the functional independence measure (FIM), by the 6-minute walk test (6MWT) and the Nottingham Health Profile (NHP). Evaluations were performed preoperatively and postoperatively. On the first day after surgery, patients in both groups showed decreased functional performance. However, the VRG showed lower reduction (45.712.3) when compared to CG (35.0612.09, P<0.05) in first postoperative day, and no significant difference in performance on discharge day (P>0.05). In evaluating the NHP field, we observed a significant decrease in pain score at third assessment (P<0.05). These patients also had a higher energy level in the first evaluation (P<0.05). There were no differences with statistical significance for emotional reactions, physical ability, and social interaction. The length of stay was significantly shorter in patients of VRG (9.410.5 days vs. 12.2 1 0.9 days, P<0.05), which also had a higher 6MWD (319.9119.3 meters vs. 263.5115.4 meters, P<0.02). Adjunctive treatment with virtual reality demonstrated benefits, with better functional performance in patients undergoing cardiac surgery.

Reproducibility of cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance for measuring left ventricular strains, torsion, and synchrony in mice.

PubMed

Haggerty, Christopher M; Kramer, Sage P; Binkley, Cassi M; Powell, David K; Mattingly, Andrea C; Charnigo, Richard; Epstein, Frederick H; Fornwalt, Brandon K

2013-08-27

Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance (CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE CMR would show excellent inter-test and inter-observer reproducibility for advanced measures of left ventricular (LV) function in mice. Five normal mice (C57BL/6) and four mice with depressed cardiac function (diet-induced obesity) were imaged twice, two days apart, on a 7T ClinScan MR system. Images were acquired with 15-20 frames per cardiac cycle in three short-axis (basal, mid, apical) and two long-axis orientations (4-chamber and 2-chamber). LV strain, twist, torsion, and measures of synchrony were quantified. Images from both days were analyzed by one observer to quantify inter-test reproducibility, while inter-observer reproducibility was assessed by a second observer's analysis of day-1 images. The coefficient of variation (CoV) was used to quantify reproducibility. LV strains and torsion were highly reproducible on both inter-observer and inter-test bases with CoVs ≤ 15%, and inter-observer reproducibility was generally better than inter-test reproducibility. However, end-systolic twist angles showed much higher variance, likely due to the sensitivity of slice location within the sharp longitudinal gradient in twist angle. Measures of synchrony including the circumferential (CURE) and radial (RURE) uniformity of strain indices, showed excellent reproducibility with CoVs of 1% and 3%, respectively. Finally, peak measures (e.g., strains) were generally more reproducible than the corresponding rates of change (e.g., strain rate). Cine DENSE CMR is a highly reproducible technique for quantification of advanced measures of left ventricular cardiac function in mice including strains, torsion and measures of synchrony. However, myocardial twist angles are not reproducible and future studies should instead report torsion.

Assessment of a low-intensity cardiac rehabilitation programme using the six-minute walk test.

PubMed

Wright, D J; Khan, K M; Gossage, E M; Saltissi, S

2001-04-01

To examine the utility of the six-minute walk test (6'WT), in assessing the effectiveness of a six-week cardiac rehabilitation programme, of which exercise training was an integral part. Royal Liverpool and Broad Green Hospitals Rehabilitation Unit. Two hundred and thirty-nine consecutive patients referred for cardiac rehabilitation were allocated to one of two groups. In group A 209 entered and 159 completed the usual rehabilitation programme whilst group B patients (n = 30) acted as a control by deferring entry to the programme for six weeks, continuing only activities of daily living. Both groups were assessed using the 6'WT, peak expiratory flow rate (PEFR) and isometric grip strength at enrolment and six weeks. At baseline, groups A and B were demographically identical without significant differences in terms of 6'WT, PEFR or grip strength. Following the study period, group A showed a significant increase in 6'WT from 314.7 +/- 76.2 to 377.3 +/- 78.6 m, in PEFR from 406.9 +/- 115.9 to 437.8 +/- 118.6 litres per minute and in grip strength from 28.8 +/- 9.31 to 30.3 +/- 8.93 kg, all p < 0.001. There were no significant changes in group B. The 6'WT proved to be a simple and effective measurement of functional capacity in patients performing cardiac rehabilitation. The clinical programme investigated successfully increased patients' functional capacity as assessed by the 6'WT. Significant improvement in PEFR and grip strength was also demonstrated, compared with a control population.

Pathological presentation of cardiac mitochondria in a rat model for chronic kidney disease.

PubMed

Bigelman, Einat; Cohen, Lena; Aharon-Hananel, Genya; Levy, Ran; Rozenbaum, Zach; Saada, Ann; Keren, Gad; Entin-Meer, Michal

2018-01-01

Mitochondria hold crucial importance in organs with high energy demand especially the heart. We investigated whether chronic kidney disease (CKD), which eventually culminates in cardiorenal syndrome, could affect cardiac mitochondria and assessed the potential involvement of angiotensin II (AngII) in the process. Male Lewis rats underwent 5/6 nephrectomy allowing CKD development for eight months or for eleven weeks. Short-term CKD rats were administered with AngII receptor blocker (ARB). Cardiac function was assessed by echocardiography and cardiac sections were evaluated for interstitial fibrosis and cardiomyocytes' hypertrophy. Electron microscopy was used to explore the spatial organization of the cardiomyocytes. Expression levels of mitochondrial content and activity markers were tested in order to delineate the underlying mechanisms for mitochondrial pathology in the CKD setting with or without ARB administration. CKD per-se resulted in induced cardiac interstitial fibrosis and cardiomyocytes' hypertrophy combined with a marked disruption of the mitochondrial structure. Moreover, CKD led to enhanced cytochrome C leakage to the cytosol and to enhanced PARP-1 cleavage which are associated with cellular apoptosis. ARB treatment did not improve kidney function but markedly reduced left ventricular mass, cardiomyocytes' hypertrophy and interstitial fibrosis. Interestingly, ARB administration improved the spatial organization of cardiac mitochondria and reduced their increased volume compared to untreated CKD animals. Nevertheless, ARB did not improve mitochondrial content, mitochondrial biogenesis or the respiratory enzyme activity. ARB mildly upregulated protein levels of mitochondrial fusion-related proteins. CKD results in cardiac pathological changes combined with mitochondrial damage and elevated apoptotic markers. We anticipate that the increased mitochondrial volume mainly represents mitochondrial swelling that occurs during the pathological process of cardiac hypertrophy. Chronic administration of ARB may improve the pathological appearance of the heart. Further recognition of the molecular pathways leading to mitochondrial insult and appropriate intervention is of crucial importance.

Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy.

PubMed

Sacre, J W; Jellis, C L; Coombes, J S; Marwick, T H

2012-09-01

Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P < 0.01). Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P < 0.05). Area under the receiver-operating characteristic curve revealed good diagnostic performance of all heart-rate recovery parameters (range 0.80-0.83, P < 0.001). Optimal cut-offs for heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P < 0.05). Post-exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo.

PubMed

Tang, Yao Liang; Qian, Keping; Zhang, Y Clare; Shen, Leping; Phillips, M Ian

2005-12-01

The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression. Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

Dynamic and quantitative evaluation of degenerative mitral valve disease: a dedicated framework based on cardiac magnetic resonance imaging.

PubMed

Sturla, Francesco; Onorati, Francesco; Puppini, Giovanni; Pappalardo, Omar A; Selmi, Matteo; Votta, Emiliano; Faggian, Giuseppe; Redaelli, Alberto

2017-04-01

Accurate quantification of mitral valve (MV) morphology and dynamic behavior over the cardiac cycle is crucial to understand the mechanisms of degenerative MV dysfunction and to guide the surgical intervention. Cardiac magnetic resonance (CMR) imaging has progressively been adopted to evaluate MV pathophysiology, although a dedicated framework is required to perform a quantitative assessment of the functional MV anatomy. We investigated MV dynamic behavior in subjects with normal MV anatomy (n=10) and patients referred to surgery due to degenerative MV prolapse, classified as fibro-elastic deficiency (FED, n=9) and Barlow's disease (BD, n=10). A CMR-dedicated framework was adopted to evaluate prolapse height and volume and quantitatively assess valvular morphology and papillary muscles (PAPs) function over the cardiac cycle. Multiple comparison was used to investigate the hallmarks associated to MV degenerative prolapse and evaluate the feasibility of anatomical and functional distinction between FED and BD phenotypes. On average, annular dimensions were significantly (P<0.05) larger in BD than in FED and normal subjects while no significant differences were noticed between FED and normal. MV eccentricity progressively decreased passing from normal to FED and BD, with the latter exhibiting a rounder annulus shape. Over the cardiac cycle, we noticed significant differences for BD during systole with an abnormal annular enlargement between mid and late systole (LS) (P<0.001 vs. normal); the PAPs dynamics remained comparable in the three groups. Prolapse height and volume highlighted significant differences among normal, FED and BD valves. Our CMR-dedicated framework allows for the quantitative and dynamic evaluation of MV apparatus, with quantifiable annular alterations representing the primary hallmark of severe MV degeneration. This may aid surgeons in the evaluation of the severity of MV dysfunction and the selection of the appropriate MV treatment.

Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy.

PubMed

Heikal, N M; Bader, F M; Martins, T B; Pavlov, I Y; Wilson, A R; Barakat, M; Stehlik, J; Kfoury, A G; Gilbert, E M; Delgado, J C; Hill, H R

2013-01-01

Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001). Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies. Published by Elsevier Inc.

Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2.

PubMed

Ganz, Patricia A; Romond, Edward H; Cecchini, Reena S; Rastogi, Priya; Geyer, Charles E; Swain, Sandra M; Jeong, Jong-Hyeon; Fehrenbacher, Louis; Gross, Howard M; Brufsky, Adam M; Flynn, Patrick J; Wahl, Tanya A; Seay, Thomas E; Wade, James L; Biggs, David D; Atkins, James N; Polikoff, Jonathan; Zapas, John L; Mamounas, Eleftherios P; Wolmark, Norman

2017-12-10

Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment. Patients and Methods Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2-positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions. Results At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a > 10% decline in left ventricular ejection fraction from baseline to a value < 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab. Conclusion In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function.

Cardiac mechanics and heart rate variability in patients with systemic sclerosis: the association that we should not miss.

PubMed

Zlatanovic, Maja; Tadic, Marijana; Celic, Vera; Ivanovic, Branislava; Stevanovic, Ana; Damjanov, Nemanja

2017-01-01

We aimed to determine left ventricular (LV) and right ventricular (RV) structure, function and mechanics, as well as heart rate variability (HRV), and their relationship, in patients with systemic sclerosis (SSc). The study included 41 SSc patients and 30 age-matched healthy volunteers. All the patients underwent clinical examination, serological tests, pulmonary function testing, 24-h Holter monitoring and complete two-dimensional echocardiography including strain analysis. The parameters of LV structure (interventricular septum thickness and LV mass index) and RV structure (RV wall thickness) were significantly higher in SSc patients. LV and RV diastolic function (estimated by mitral and tricuspid E/e' ratio) was significantly impaired in SSc group comparing with the healthy controls. LV and RV longitudinal function was significantly deteriorated in SSc patients. LV circumferential strain was also significantly lower in SSc group, whereas LV radial strain was similar between the observed groups. All parameters of time and frequency domain of HRV were decreased in SSc patients. LV and RV cardiac remodeling parameters, particularly diastolic function and longitudinal strain, were associated with HRV indices without regard to the main demographic or the clinical and echocardiographic characteristics. Rodnan Skin Score was also independently associated with biventricular cardiac remodeling in SSc patients. LV and RV structure, function and mechanics, as well as autonomic nervous function, were significantly impaired in SSc patients. There is the significant association between biventricular cardiac remodeling and autonomic function in these patients, which could be useful for their everyday clinical assessment.

Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

PubMed

Jonker, Jacqueline T; de Mol, Pieter; de Vries, Suzanna T; Widya, Ralph L; Hammer, Sebastiaan; van Schinkel, Linda D; van der Meer, Rutger W; Gans, Rijk O B; Webb, Andrew G; Kan, Hermien E; de Koning, Eelco J P; Bilo, Henk J G; Lamb, Hildo J

2013-11-01

To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P < .01), and subcutaneous abdominal fat volume remained unchanged (P = .9). Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P < .01) and paracardial fat volume from 4.6 mL ± 0.9 to 3.7 mL ± 0.8 (P = .02). Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

Non-motor symptoms and cardiac innervation in SYNJ1-related parkinsonism.

PubMed

De Rosa, A; Pellegrino, T; Pappatà, S; Lieto, M; Bonifati, V; Palma, V; Topa, A; Santoro, L; Bilo, L; Cuocolo, A; De Michele, G

2016-02-01

PARK20 is a rare autosomal recessive parkinsonism related to the SYNJ1 gene and characterized by early-onset of disease and atypical signs such as supranuclear vertical gaze palsy, dementia, dystonia, and generalized tonic-clonic seizures. Non-motor features and cardiac sympathetic innervation were assessed in two siblings affected by parkinsonism who harboured the homozygous Arg258Gln mutation in the SYNJ1 gene. The Non-Motor Symptoms, the SCOPA-AUT, the Mayo Sleep Questionnaires and polysomnography were used to investigate non-motor signs (NMS), autonomic dysfunction and REM Behavioural Disorder (RBD). Cognitive functions were examined by an extensive battery of neuropsychological tests. In addition, motor and sensory nerve conduction studies and evoked laser potentials were performed. Cardiac sympathetic innervation was assessed in the two patients by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, computing early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR). Among the non-motor symptoms and autonomic signs, case 1 had cold intolerance, drooling and dysphagia, while case 2 had pain and urinary dysfunction. Both cases showed mood and behavioural disorders. RBD were not found, whereas the neuropsychological assessment revealed a progressive cognitive impairment. Neurophysiological studies revealed no abnormalities. Indexes of cardiac sympathetic innervation in the two patients did not differ from those of control subjects. Our findings expand the phenotypic profile of SYNJ1-related parkinsonism. Preserved cardiac sympathetic function and absence of RBD suggest that PARK20 should be explained by a pathogenic mechanism different from Lewy Body pathology, or that the latter is not as widespread as idiopathic Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

A single bout of exhaustive exercise affects integrated baroreflex function after 16 days of head-down tilt

NASA Technical Reports Server (NTRS)

Engelke, K. A.; Doerr, D. F.; Convertino, V. A.

1995-01-01

We tested the hypothesis that one bout of maximal exercise performed 24 h before reambulation from 16 days of 6 degrees head-down tilt (HDT) could increase integrated baroreflex sensitivity. Isolated carotid-cardiac and integrated baroreflex function was assessed in seven subjects before and after two periods of HDT separated by 11 mo. On the last day of one HDT period, subjects performed a single bout of maximal cycle ergometry (exercise). Subjects did not exercise after the other HDT period (control). Carotid-cardiac baroreflex sensitivity was evaluated using a neck collar device. Integrated baroreflex function was assessed by recording heart rate (HR) and blood pressure (MAP) during a 15-s Valsalva maneuver (VM) at a controlled expiratory pressure of 30 mmHg. The ratio of change in HR to change in MAP (delta HR/ delta MAP) during phases II and IV of the VM was used as an index of cardiac baroreflex sensitivity. Baroreflex-mediated vasoconstriction was assessed by measuring the late phase II rise in MAP. Following HDT, carotid-cardiac baroreflex sensitivity was reduced (2.8 to 2.0 ms/mmHg; P = 0.05) as was delta HR/ delta MAP during phase II (-1.5 to -0.8 beats/mmHg; P = 0.002). After exercise, isolated carotid baroreflex activity and phase II delta HR/ delta MAP returned to pre-HDT levels but remained attenuated in the control condition. Phase IV delta HR/ delta MAP was not altered by HDT or exercise. The late phase II increase of MAP was 71% greater after exercise compared with control (7 vs. 2 mmHg; P = 0.041).(ABSTRACT TRUNCATED AT 250 WORDS).

Heart Performance Determination by Visualization in Larval Fishes: Influence of Alternative Models for Heart Shape and Volume

PubMed Central

Perrichon, Prescilla; Grosell, Martin; Burggren, Warren W.

2017-01-01

Understanding cardiac function in developing larval fishes is crucial for assessing their physiological condition and overall health. Cardiac output measurements in transparent fish larvae and other vertebrates have long been made by analyzing videos of the beating heart, and modeling this structure using a conventional simple prolate spheroid shape model. However, the larval fish heart changes shape during early development and subsequent maturation, but no consideration has been made of the effect of different heart geometries on cardiac output estimation. The present study assessed the validity of three different heart models (the “standard” prolate spheroid model as well as a cylinder and cone tip + cylinder model) applied to digital images of complete cardiac cycles in larval mahi-mahi and red drum. The inherent error of each model was determined to allow for more precise calculation of stroke volume and cardiac output. The conventional prolate spheroid and cone tip + cylinder models yielded significantly different stroke volume values at 56 hpf in red drum and from 56 to 104 hpf in mahi. End-diastolic and stroke volumes modeled by just a simple cylinder shape were 30–50% higher compared to the conventional prolate spheroid. However, when these values of stroke volume multiplied by heart rate to calculate cardiac output, no significant differences between models emerged because of considerable variability in heart rate. Essentially, the conventional prolate spheroid shape model provides the simplest measurement with lowest variability of stroke volume and cardiac output. However, assessment of heart function—especially if stroke volume is the focus of the study—should consider larval heart shape, with different models being applied on a species-by-species and developmental stage-by-stage basis for best estimation of cardiac output. PMID:28725199

Notch3/Akt signaling contributes to OSM-induced protection against cardiac ischemia/reperfusion injury.

PubMed

Zhang, Mingming; Wang, Chen; Hu, Jianqiang; Lin, Jie; Zhao, Zhijing; Shen, Min; Gao, Haokao; Li, Na; Liu, Min; Zheng, Pengfei; Qiu, Cuiting; Gao, Erhe; Wang, Haichang; Sun, Dongdong

2015-09-01

Oncostatin M (OSM) exhibits many unique biological activities by activating the Oβ receptor. However, its role in myocardial ischemia/reperfusion injury (I/R injury) in mice remains unknown. We investigated whether Notch3/Akt signaling is involved in the regulation of OSM-induced protection against cardiac I/R injury. The effects of OSM were assessed in mice that underwent myocardial I/R injury by OSM treatment or by genetic deficiency of the OSM receptor Oβ. We investigated its effects on cardiomyocyte apoptosis and mitochondrial biogenesis and whether Notch3/Akt signaling was involved in the regulation of OSM-induced protection against cardiac I/R injury. The mice underwent 30 min of ischemia followed by 3 h of reperfusion and were randomized to be treated with Notch3 siRNA (siNotch3) or lentivirus carrying Notch3 cDNA (Notch3) 72 h before coronary artery ligation. Myocardial infarct size, cardiac function, cardiomyocyte apoptosis and mitochondria morphology in mice that underwent cardiac I/R injury were compared between groups. OSM alleviated cardiac I/R injury by inhibiting cardiomyocyte apoptosis through promotion of Notch3 production, thus activating the PI3K/Akt pathway. OSM enhanced mitochondrial biogenesis and mitochondrial function in mice subjected to cardiac I/R injury. In contrast, OSM receptor Oβ knock out exacerbated cardiac I/R injury, decreased Notch3 production, enhanced cardiomyocyte apoptosis, and impaired mitochondrial biogenesis in cardiac I/R injured mice. The mechanism of OSM on cardiac I/R injury is partly mediated by the Notch3/Akt pathway. These results suggest a novel role of Notch3/Akt signaling that contributes to OSM-induced protection against cardiac I/R injury.

Is plasma N-BNP a good indicator of the functional reserve of failing hearts? The FRESH-BNP study.

PubMed

Williams, Simon G; Ng, Leong L; O'Brien, Russell J; Taylor, Steve; Wright, D Jay; Tan, Lip-Bun

2004-12-01

Whether plasma N-terminal brain natriuretic peptide (N-BNP) is useful in the diagnosis of heart failure (HF) depends traditionally on whether it is as good as the putative 'gold-standard', left ventricular ejection fraction (LVEF), in indicating cardiac dysfunction. However, since HF is primarily an impairment of function of the cardiac pump, we explored the relationship between N-BNP and direct and indirect indicators of cardiac pump dysfunction. Eighty-six HF patients (mean age 56 years) with a range of LVEF's (mean 36.9+/-15.2%, range 15-66%) and 10 age-matched healthy controls were recruited into the study and had resting N-BNP measured. Cardiopulmonary exercise testing was performed to assess peak oxygen consumption (Vo(2)). A subgroup of 23 subjects underwent further exercise haemodynamic assessment to evaluate peak cardiac power output (CPO). The CHF group had significantly higher N-BNP (median [interquartile range]) levels (299 [705] fmol/ml) than the control group (7 [51] fmol/ml, P<0.005). Significant correlations between N-BNP and peak Vo(2), and N-BNP and peak CPO were observed (R> or =0.5, P<0.005). Although significant correlation was observed between N-BNP and LVEF (R=0.34, P=0.01), the correlations between LVEF and peak Vo(2) or peak CPO (all R<0.3, P>0.3) were not significant. Multivariate analysis identified plasma N-BNP and NYHA class, but not LVEF, as independent predictors of peak Vo(2). We have found that N-BNP was surprisingly good as a simple indicator of cardiac pump dysfunction. Since heart failure is an inadequacy of function, these results strongly support the notion that N-BNP is a useful blood test in estimating the extent of cardiac pump dysfunction and helpful in establishing positive diagnosis of heart failure.

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress.

PubMed

Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2016-01-01

The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=-0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=-0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=-0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction, inflammation, and oxidative stress.

Cardiac output by pulse contour analysis does not match the increase measured by rebreathing during human spaceflight.

PubMed

Hughson, Richard L; Peterson, Sean D; Yee, Nicholas J; Greaves, Danielle K

2017-11-01

Pulse contour analysis of the noninvasive finger arterial pressure waveform provides a convenient means to estimate cardiac output (Q̇). The method has been compared with standard methods under a range of conditions but never before during spaceflight. We compared pulse contour analysis with the Modelflow algorithm to estimates of Q̇ obtained by rebreathing during preflight baseline testing and during the final month of long-duration spaceflight in nine healthy male astronauts. By Modelflow analysis, stroke volume was greater in supine baseline than seated baseline or inflight. Heart rate was reduced in supine baseline so that there were no differences in Q̇ by Modelflow estimate between the supine (7.02 ± 1.31 l/min, means ± SD), seated (6.60 ± 1.95 l/min), or inflight (5.91 ± 1.15 l/min) conditions. In contrast, rebreathing estimates of Q̇ increased from seated baseline (4.76 ± 0.67 l/min) to inflight (7.00 ± 1.39 l/min, significant interaction effect of method and spaceflight, P < 0.001). Pulse contour analysis utilizes a three-element Windkessel model that incorporates parameters dependent on aortic pressure-area relationships that are assumed to represent the entire circulation. We propose that a large increase in vascular compliance in the splanchnic circulation invalidates the model under conditions of spaceflight. Future spaceflight research measuring cardiac function needs to consider this important limitation for assessing absolute values of Q̇ and stroke volume. NEW & NOTEWORTHY Noninvasive assessment of cardiac function during human spaceflight is an important tool to monitor astronaut health. This study demonstrated that pulse contour analysis of finger arterial blood pressure to estimate cardiac output failed to track the 46% increase measured by a rebreathing method. These results strongly suggest that alternative methods not dependent on pulse contour analysis are required to track cardiac function in spaceflight. Copyright © 2017 the American Physiological Society.

[Assessment of Tricuspid Insufficiency and the Function of Right Ventricle Using Cardiac Magnetic Resonance Imaging Combined with Echocardiography].

PubMed

Chen, Hui; Zhao, Yanling; Yu, Jianqun

2015-08-01

Right-sided cardiac valvular diseases have traditionally been considered less important than disease of mitral or aortic valve. However, severe tricuspid regurgitation could lead to right ventricle dysfunction and reduce patients' survival rate. In clinic setting, tricuspid valve disease should be paid more attention for patients with secondary tricuspid regurgitation caused by left-sided valvular surgery combined with irreversible annular dilatation increasing the risk of reoperation. In this review, we summarize the epidemiology, anatomy, pathology, diagnosis, ultrasound and cardiac magnetic resonance imaging findings in patients with tricuspid regurgitation.

[Cardiac structure and function in patients with obstructive sleep apnea syndrome and co-prevalent arterial hypertension. Influence of CPAP therapy].

PubMed

Duchna, Hans-Werner; Myslinski, Wojciech; Dichmann, Manuel; Rasche, Kurt; Schultze-Werninghaus, Gerhard; Orth, Maritta

2006-01-15

30% of patients with arterial hypertension (AH) are supposed to have a co-prevalent obstructive sleep apnea syndrome (OSAS). Hence, the influence of CPAP (continuous positive airway pressure) therapy on cardiac structure and function was investigated in medically treated patients with AH and co-prevalent OSAS. In all patients AH was treated for at least 5 years. Matched pairs concerning anthropometric data, medical therapy and duration of AH, and severity of OSAS were investigated: 20 patients with untreated OSAS were compared to 20 patients with CPAP therapy for at least 6 months. Further cardiopulmonary diseases were excluded. Cardiac structure and function were assessed echocardiographically. Patients under CPAP therapy had significantly better diastolic left ventricular function, a lower left ventricular mass index, and significantly less frequent signs of left ventricular (eccentric) hypertrophy than patients with untreated OSAS. Furthermore, differences were significant concerning right ventricular wall thickness and mean pulmonary artery pressure. CPAP therapy positively influences left and right cardial structure and function in addition to antihypertensive medication in patients with AH and co-prevalent OSAS.

Determinants of distance walked during the six-minute walk test in patients undergoing cardiac surgery at hospital discharge

PubMed Central

2014-01-01

Introduction The aim of this study was to identify the determinants of distance walked in six-minute walk test (6MWD) in patients undergoing cardiac surgery at hospital discharge. Methods The assessment was performed preoperatively and at discharge. Data from patient records were collected and measurement of the Functional Independence Measure (FIM) and the Nottingham Health Profile (NHP) were performed. The six-minute walk test (6MWT) was performed at discharge. Patients undergoing elective cardiac surgery, coronary artery bypass grafting or valve replacement were eligible. Patients older than 75 years who presented arrhythmia during the protocol, with psychiatric disorders, muscular or neurological disorders were excluded from the study. Results Sixty patients (44.26% male, mean age 51.53 ± 13 years) were assessed. In multivariate analysis the following variables were selected: type of surgery (P = 0.001), duration of cardiopulmonary bypass (CPB) (P = 0.001), Functional Independence Measure - FIM (0.004) and body mass index - BMI (0.007) with r = 0.91 and r2 = 0.83 with P < 0.001. The equation derived from multivariate analysis: 6MWD = Surgery (89.42) + CPB (1.60) + MIF (2.79 ) - BMI (7.53) - 127.90. Conclusion In this study, the determinants of 6MWD in patients undergoing cardiac surgery were: the type of surgery, CPB time, functional capacity and body mass index. PMID:24885130

Novel cardiovascular magnetic resonance oxygenation approaches in understanding pathophysiology of cardiac diseases.

PubMed

Sree Raman, Karthigesh; Nucifora, Gaetano; Selvanayagam, Joseph B

2018-05-01

Cardiovascular magnetic resonance imaging (CMR) permits accurate phenotyping of many cardiac diseases. CMR's inherent advantages are its non-invasive nature, lack of ionizing radiation and high accuracy and reproducibility. Furthermore, it is able to assess many aspects of cardiac anatomy, structure and function. Specifically, it can characterize myocardial tissue, myocardial function, myocardial mass, myocardial blood flow/perfusion, irreversible and reversible injury, all with a high degree of accuracy and reproducibility. Hence, CMR is a powerful tool in clinical and pre-clinical research. In recent years there have been novel advances in CMR myocardial tissue characterization. Oxygenation-sensitive CMR (OS-CMR) is a novel non-invasive, contrast independent technique that permits direct quantification of myocardial tissue oxygenation, both at rest and during stress. In this review, we will address the principles of the OS-CMR technique, its recent advances and summarize the studies in the effects of oxygenation on cardiac diseases. © 2018 John Wiley & Sons Australia, Ltd.

Advances in cardiac CT contrast injection and acquisition protocols.

PubMed

Scholtz, Jan-Erik; Ghoshhajra, Brian

2017-10-01

Cardiac computed tomography (CT) imaging has become an important part of modern cardiovascular care. Coronary CT angiography (CTA) is the first choice imaging modality for non-invasive visualization of coronary artery stenosis. In addition, cardiac CT does not only provide anatomical evaluation, but also functional and valvular assessment, and myocardial perfusion evaluation. In this article we outline the factors which influence contrast enhancement, give an overview of current contrast injection and acquisition protocols, with focus on current emerging topics such as pre-transcatheter aortic valve replacement (TAVR) planning, cardiac CT for congenital heart disease (CHD) patients, and myocardial CT perfusion (CTP). Further, we point out areas where we see potential for future improvements in cardiac CT imaging based on a closer interaction between CT scanner settings and contrast injection protocols to tailor injections to patient- and exam-specific factors.

Advances in cardiac CT contrast injection and acquisition protocols

PubMed Central

Scholtz, Jan-Erik

2017-01-01

Cardiac computed tomography (CT) imaging has become an important part of modern cardiovascular care. Coronary CT angiography (CTA) is the first choice imaging modality for non-invasive visualization of coronary artery stenosis. In addition, cardiac CT does not only provide anatomical evaluation, but also functional and valvular assessment, and myocardial perfusion evaluation. In this article we outline the factors which influence contrast enhancement, give an overview of current contrast injection and acquisition protocols, with focus on current emerging topics such as pre-transcatheter aortic valve replacement (TAVR) planning, cardiac CT for congenital heart disease (CHD) patients, and myocardial CT perfusion (CTP). Further, we point out areas where we see potential for future improvements in cardiac CT imaging based on a closer interaction between CT scanner settings and contrast injection protocols to tailor injections to patient- and exam-specific factors. PMID:29255688

Direct volume estimation without segmentation

NASA Astrophysics Data System (ADS)

Zhen, X.; Wang, Z.; Islam, A.; Bhaduri, M.; Chan, I.; Li, S.

2015-03-01

Volume estimation plays an important role in clinical diagnosis. For example, cardiac ventricular volumes including left ventricle (LV) and right ventricle (RV) are important clinical indicators of cardiac functions. Accurate and automatic estimation of the ventricular volumes is essential to the assessment of cardiac functions and diagnosis of heart diseases. Conventional methods are dependent on an intermediate segmentation step which is obtained either manually or automatically. However, manual segmentation is extremely time-consuming, subjective and highly non-reproducible; automatic segmentation is still challenging, computationally expensive, and completely unsolved for the RV. Towards accurate and efficient direct volume estimation, our group has been researching on learning based methods without segmentation by leveraging state-of-the-art machine learning techniques. Our direct estimation methods remove the accessional step of segmentation and can naturally deal with various volume estimation tasks. Moreover, they are extremely flexible to be used for volume estimation of either joint bi-ventricles (LV and RV) or individual LV/RV. We comparatively study the performance of direct methods on cardiac ventricular volume estimation by comparing with segmentation based methods. Experimental results show that direct estimation methods provide more accurate estimation of cardiac ventricular volumes than segmentation based methods. This indicates that direct estimation methods not only provide a convenient and mature clinical tool for cardiac volume estimation but also enables diagnosis of cardiac diseases to be conducted in a more efficient and reliable way.

Echocardiographic assessment of cardiac disease

NASA Technical Reports Server (NTRS)

Popp, R. L.

1976-01-01

The physical principles and current applications of echocardiography in assessment of heart diseases are reviewed. Technical considerations and unresolved points relative to the use of echocardiography in various disease states are stressed. The discussion covers normal mitral valve motion, mitral stenosis, aortic regurgitation, atrial masses, mitral valve prolapse, and idiopathic hypertrophic subaortic stenosis. Other topics concern tricuspic valve abnormalities, aortic valve disease, pulmonic valve, pericardial effusion, intraventricular septal motion, and left ventricular function. The application of echocardiography to congenital heart disease diagnosis is discussed along with promising ultrasonic imaging systems. The utility of echocardiography in quantitative evaluation of cardiac disease is demonstrated.

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

PubMed

Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury

PubMed Central

West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V

2014-01-01

Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day−1, 5 days week−1 for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI. PMID:24535438

Cardiovascular dynamics of Canadian Indigenous peoples.

PubMed

Foulds, Heather J A; Bredin, Shannon S D; Warburton, Darren E R

2018-12-01

Limited understanding of Indigenous adults' cardiovascular structure and function exists despite high rates of cardiovascular disease. This investigation characterised cardiovascular structure and function among young Indigenous adults and compared to age- and sex-matched European descendants. Echocardiographic assessments included apical two- and four-chamber images, parasternal short-axis images and Doppler. Analyses included cardiac volumes, dimensions, velocities and strains. Cardiovascular structure and function were similar between Indigenous (n=10, 25 ± 3 years, 4 women) and European-descendant (n=10, 24 ± 4 years, 4 women,) adults, though European descendants demonstrated greater systemic vascular resistance (18.19 ± 3.94 mmHg∙min -1 ∙L -1 vs. 15.36 ± 2.97 mmHg∙min -1 ∙L -1 , p=0.03). Among Indigenous adults, women demonstrated greater arterial elastance (0.80 ± 0.15 mmHg·mL -1 ·m -2 vs. 0.55 ± 0.17 mmHg·mL -1 ·m -2 , p=0.02) and possibly greater systemic vascular resistance (17.51 ± 2.20 mmHg∙min -1 ∙L -1 vs. 13.93 ± 2.61 mmHg∙min -1 ∙L -1 , p=0.07). Indigenous men had greater cardiac size, dimensions and output, though body size differences accounted for cardiac size differences. Similar cardiac rotation and strains were observed across sexes. Arterial elastance and cardiac size were different between Indigenous men and women while cardiovascular structure and function may be similar between Indigenous and European descendants.

Cognitive function in patients with stable coronary heart disease: Related cerebrovascular and cardiovascular responses.

PubMed

Gayda, Mathieu; Gremeaux, Vincent; Bherer, Louis; Juneau, Martin; Drigny, Joffrey; Dupuy, Olivier; Lapierre, Gabriel; Labelle, Véronique; Fortier, Annik; Nigam, Anil

2017-01-01

Chronic exercise has been shown to prevent or slow age-related decline in cognitive functions in otherwise healthy, asymptomatic individuals. We sought to assess cognitive function in a stable coronary heart disease (CHD) sample and its relationship to cerebral oxygenation-perfusion, cardiac hemodynamic responses, and [Formula: see text] peak compared to age-matched and young healthy control subjects. Twenty-two young healthy controls (YHC), 20 age-matched old healthy controls (OHC) and 25 patients with stable CHD were recruited. Cognitive function assessment included short term-working memory, perceptual abilities, processing speed, cognitive inhibition and flexibility and long-term verbal memory. Maximal cardiopulmonary function (gas exchange analysis), cardiac hemodynamic (impedance cardiography) and left frontal cerebral oxygenation-perfusion (near-infra red spectroscopy) were measured during and after a maximal incremental ergocycle test. Compared to OHC and CHD, YHC had higher [Formula: see text] peak, maximal cardiac index (CI max), cerebral oxygenation-perfusion (ΔO2 Hb, ΔtHb: exercise and recovery) and cognitive function (for all items) (P<0.05). Compared to OHC, CHD patients had lower [Formula: see text] peak, CI max, cerebral oxygenation-perfusion (during recovery) and short term-working memory, processing speed, cognitive inhibition and flexibility and long-term verbal memory (P<0.05). [Formula: see text] peak and CI max were related to exercise cerebral oxygenation-perfusion and cognitive function (P<0.005). Cerebral oxygenation-perfusion (exercise) was related to cognitive function (P<0.005). Stable CHD patients have a worse cognitive function, a similar cerebral oxygenation/perfusion during exercise but reduced one during recovery vs. their aged-matched healthy counterparts. In the all sample, cognitive functions correlated with [Formula: see text] peak, CI max and cerebral oxygenation-perfusion.

USPIO-enhanced 3D-cine self-gated cardiac MRI based on a stack-of-stars golden angle short echo time sequence: Application on mice with acute myocardial infarction.

PubMed

Trotier, Aurélien J; Castets, Charles R; Lefrançois, William; Ribot, Emeline J; Franconi, Jean-Michel; Thiaudière, Eric; Miraux, Sylvain

2016-08-01

To develop and assess a 3D-cine self-gated method for cardiac imaging of murine models. A 3D stack-of-stars (SOS) short echo time (STE) sequence with a navigator echo was performed at 7T on healthy mice (n = 4) and mice with acute myocardial infarction (MI) (n = 4) injected with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. In all, 402 spokes were acquired per stack with the incremental or the golden angle method using an angle increment of (360/402)° or 222.48°, respectively. A cylindrical k-space was filled and repeated with a maximum number of repetitions (NR) of 10. 3D cine cardiac images at 156 μm resolution were reconstructed retrospectively and compared for the two methods in terms of contrast-to-noise ratio (CNR). The golden angle images were also reconstructed with NR = 10, 6, and 3, to assess cardiac functional parameters (ejection fraction, EF) on both animal models. The combination of 3D SOS-STE and USPIO injection allowed us to optimize the identification of cardiac peaks on navigator signal and generate high CNR between blood and myocardium (15.3 ± 1.0). The golden angle method resulted in a more homogeneous distribution of the spokes inside a stack (P < 0.05), enabling reducing the acquisition time to 15 minutes. EF was significantly different between healthy and MI mice (P < 0.05). The method proposed here showed that 3D-cine images could be obtained without electrocardiogram or respiratory gating in mice. It allows precise measurement of cardiac functional parameters even on MI mice. J. Magn. Reson. Imaging 2016;44:355-365. © 2016 Wiley Periodicals, Inc.

Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation.

PubMed

Bai, Yang; Cui, Wenpeng; Xin, Ying; Miao, Xiao; Barati, Michelle T; Zhang, Chi; Chen, Qiang; Tan, Yi; Cui, Taixing; Zheng, Yang; Cai, Lu

2013-04-01

This study was to investigate whether sulforaphane (SFN) can prevent diabetic cardiomyopathy. Type 1 diabetes was induced in FVB mice by multiple intraperitoneal injections with low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without SFN at 0.5mg/kg daily in five days of each week for 3 months and then kept until 6 months. At 3 and 6 months of diabetes, blood pressure and cardiac function were assessed. Cardiac fibrosis, inflammation, and oxidative damage were assessed by Western blot, real-time qPCR, and histopathological examination. SFN significantly prevented diabetes-induced high blood pressure and cardiac dysfunction at both 3 and 6 months, and also prevented diabetes-induced cardiac hypertrophy (increased the ratio of heart weight to tibia length and the expression of atrial natriuretic peptide mRNA and protein) and fibrosis (increased the accumulation of collagen and expression of connective tissue growth factor and tissue growth factor-β). SFN also almost completely prevented diabetes-induced cardiac oxidative damage (increased accumulation of 3-nitrotyrosine and 4-hydroxynonenal) and inflammation (increased tumor necrotic factor-α and plasminogen activator inhibitor 1 expression). SFN up-regulated NFE2-related factor 2 (Nrf2) expression and transcription activity that was reflected by increased Nrf2 nuclear accumulation and phosphorylation as well as the mRNA and protein expression of Nrf2 downstream antioxidants. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the SFN's prevention of high glucose-induced fibrotic response. These results suggest that diabetes-induced cardiomyopathy can be prevented by SFN, which was associated with the up-regulated Nrf2 expression and transcription function. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chronic AMPK activity dysregulation produces myocardial insulin resistance in the human Arg302Gln-PRKAG2 glycogen storage disease mouse model

PubMed Central

2013-01-01

Background The cardiac PRKAG2 mutation in the γ2-subunit of adenosine monophosphate activated kinase (AMPK) is characterized by excessive glycogen deposition, hypertrophy, frequent arrhythmias, and progressive conduction system disease. We investigated whether myocardial glucose uptake (MGU) was augmented following insulin stimulation in a mouse model of the PRKAG2 cardiac syndrome. Methods Myocardial and skeletal muscle glucose uptake was assessed with 2-[18F]fluoro-2-deoxyglucose positron emission tomography imaging in n = 3 transgenic wildtype (TGwt) vs n = 7 PRKAG2 mutant (TGmut) mice at baseline and 1 week later, 30 min following acute insulin. Systolic function, cardiac glycogen stores, phospho-AMPK α, and insulin-receptor expression levels were analyzed to corroborate to the in vivo findings. Results TGmut Patlak Ki was reduced 56% at baseline compared to TGwt (0.3 ± 0.2 vs 0.7 ± 0.1, t test p = 0.01). MGU was augmented 71% in TGwt mice following acute insulin from baseline (0.7 ± 0.1 to 1.2 ± 0.2, t test p < 0.05). No change was observed in TGmut mice. As expected for this cardiac specific transgene, skeletal muscle was unaffected at baseline with a 33% to 38% increase (standard uptake values) for both genotypes following insulin stimulation. TGmut mice had a 47% reduction in systolic function with a fourfold increase in cardiac glycogen stores correlated with a 29% reduction in phospho-AMPK α levels. There was no difference in cardiac insulin receptor expression between mouse genotypes. Conclusions These results demonstrate a correlation between insulin resistance and AMPK activity and provide the basis for the use of this animal model for assessing metabolic therapy in the treatment of affected PRKAG2 patients. PMID:23829931

Long term effects of fetal undernutrition on rat heart. Role of hypertension and oxidative stress

PubMed Central

Rodríguez-Rodríguez, Pilar; López de Pablo, Angel L.; García-Prieto, Concha F.; Somoza, Beatriz; Quintana-Villamandos, Begoña; Gómez de Diego, José J.; Gutierrez-Arzapalo, Perla Y.; Ramiro-Cortijo, David; González, M. Carmen

2017-01-01

Background and aims Fetal undernutrition is a risk factor for heart disease in both genders, despite the protection of women against hypertension development. Using a rat model of maternal undernutrition (MUN) we aimed to assess possible sex differences in the development of cardiac alterations and the implication of hypertension and cardiac oxidative stress. Methods Male and female offspring from rats fed ad libitum (control) or with 50% of the normal daily intake during the second half of gestation (MUN) were used. Heart weight/body weight ratio (HW/BW), hemodynamic parameters (anaesthetized rats) and plasma brain natriuretic peptide (BNP, ELISA) were assessed in 21-day, 6-month and 22-month old rats. Plasma testosterone (ELISA) and cardiac protein expression of enzymes related to reactive oxygen species synthesis (p22phox, xanthine-oxidase) and degradation (catalase, Cu/Zn-SOD, Mn-SOD, Ec-SOD) were evaluated in 21-day and 6-month old rats (Western Blot). Heart structure and function was studied at the age of 22 months (echocardiography). Results At the age of 21 days MUN males exhibited significantly larger HW/BW and cardiac p22phox expression while females had reduced p22phox expression, compared to their respective sex-matched controls. At the age of 6-months, MUN males showed significantly larger blood pressure and cardiac xanthine-oxidase expression; MUN females were normotensive and had a lower cardiac expression of antioxidant enzymes, compared to their respective sex-matched controls. At the age of 22 months, both MUN males and females showed larger HW/BW and left ventricular mass and lower ejection fraction compared to sex-matched controls; only MUN males exhibited hypertension and a larger plasma BNP compared to aged male controls. Conclusions 1) During perinatal life females exposed to fetal undernutrition are protected from cardiac alterations, but in ageing they exhibit ventricular hypertrophy and functional loss, like MUN males; 2) cardiac oxidative stress might be implicated in the observed heart alterations in both sexes and 3) the severity of cardiac damage might be greater in males due to hypertension. PMID:28212445

Vitamin D deficiency and its relationship with cardiac iron and function in patients with transfusion-dependent thalassemia at Chiang Mai University Hospital.

PubMed

Dejkhamron, Prapai; Wejaphikul, Karn; Mahatumarat, Tuanjit; Silvilairat, Suchaya; Charoenkwan, Pimlak; Saekho, Suwit; Unachak, Kevalee

2018-02-01

Vitamin D deficiency is common in patients with thalassemia. Vitamin D deficiency could be related to cardiac dysfunction. Increased parathyroid hormone (PTH) is also known to be associated with heart failure. To determine the prevalence of Vitamin D deficiency and to explore the impact of Vitamin D deficiency on cardiac iron and function in patients with transfusion-dependent thalassemia. A cross-sectional study in patients with Transfusion-dependent thalassemia was conducted. Patients with liver disease, renal disease, type 1 diabetes, malabsorption, hypercortisolism, malignancy, and contraindication for MRI were excluded. Calcium, phosphate, PTH, vitamin D-25OH were measured. CardiacT2 * and liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) were determined. Results Sixty-one (33M/28F) patients with Transfusion-dependent thalassemia were enrolled. The prevalence of Vitamin D deficiency was 50.8%. Patients with cardiac siderosis had tendency for lower D-25OH than those without siderosis (15.9 (11.7-20.0) vs. 20.2 (15.85-22.3) ng/mL); p = 0.06). Serum calcium, phosphate, PTH, LIC, cardiac T2 * , and LVEF were not different between the groups with or without Vitamin D deficiency. Patients with Vitamin D deficiency had significantly lower hemoglobin levels compared to those without Vitamin D deficiency (7.5 (6.93-8.33) vs. 8.1 (7.30-8.50) g/dL; p = 0.04). The median hemoglobin in the last 12 months was significantly correlated with D-25OH. Cardiac T2 * had significant correlation with PTH. Vitamin D deficiency is prevalent in patients with Transfusion-dependent thalassemia. Vitamin D level is correlated with hemoglobin level. Vitamin D status should be routinely assessed in these patients. Low PTH is correlated with increased cardiac iron. This study did not demonstrate an association between Vitamin D deficiency and cardiac iron or function in patients with Transfusion-dependent thalassemia.

Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model.

PubMed

Daltro, P S; Barreto, B C; Silva, P G; Neto, P Chenaud; Sousa Filho, P H F; Santana Neta, D; Carvalho, G B; Silva, D N; Paredes, B D; de Alcantara, A C; Freitas, L A R; Couto, R D; Santos, R R; Souza, B S F; Soares, M B P; Macambira, S G

2017-10-01

Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity. After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated. Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis. Characterization of CM by protein array showed the presence of different cytokines and growth factors, including chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I, adiponectin, transforming growth factor (TGF) β, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis. Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due to obesity and corroborate to the paracrine action of MSCs in heart disease models. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

PubMed

Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

2016-12-01

Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unexpected and rapid recovery of left ventricular function in patients with peripartum cardiomyopathy: impact of cardiac resynchronization therapy.

PubMed

Mouquet, Frederic; Mostefa Kara, Meriem; Lamblin, Nicolas; Coulon, Capucine; Langlois, Stephane; Marquie, Christelle; de Groote, Pascal

2012-05-01

Aim Peripartum cardiomyopathy (PPCM) is a rare cause of dilated cardiomyopathy responsible for heart failure toward the end of pregnancy, which can lead to chronic heart failure in 50% of cases. In this short report, we assessed the benefit of cardiac resynchronization in patients with PPCM and chronic systolic dysfunction despite optimal medical treatment. For the last 10 years, we managed eight patients diagnosed with PPCM. Two of them presented severe systolic dysfunction, and medical treatment resulted in limited improvement from 10% to 25% and from 25% to 28% despite optimal treatment for 9 and 6 years, respectively. These two patients were porposed to receive an implantatable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT). Six months after ICD-CRT treatment, we observed a significant improvement in systolic function from 25% to 45% and 28% to 50%, respectively, and positive remodelling with reduction of left ventricular end-diastolic volume from 216 to 144 mL and from 354 to 105 mL, which represent a 34% and a 70% reduction, respectively. Physicians in charge of patients with PPCM should offer the opportunity of CRT for patients whose cardiac function has not significantly improved under standard medical treatment.

Assessing the effect of preoperative levosimendan on renal function in patients with right ventricular dysfunction.

PubMed

Guerrero Orriach, Jose L; Galán Ortega, M; Ramírez Fernandez, A; Ariza Villanueva, D; Florez Vela, A; Moreno Cortés, I; Rubio Navarro, M; Cruz Mañas, J

2017-02-01

The Acute Kidney Injury Network (AKIN) classification considers SCr values, urea and urine output in order to improve timely diagnose ARF and improve patient prognosis by early treatment. Preoperative levosimendan is a new way for cardiac and kidney protection, we try to evaluate this drug in fifteen patients comparing values of AKIN scale parameters pre and post cardiac surgery in patients with right ventricle dysfunction.

Left atrial function in heart failure with impaired and preserved ejection fraction.

PubMed

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Evaluation of training nurses to perform semi-automated three-dimensional left ventricular ejection fraction using a customised workstation-based training protocol.

PubMed

Guppy-Coles, Kristyan B; Prasad, Sandhir B; Smith, Kym C; Hillier, Samuel; Lo, Ada; Atherton, John J

2015-06-01

We aimed to determine the feasibility of training cardiac nurses to evaluate left ventricular function utilising a semi-automated, workstation-based protocol on three dimensional echocardiography images. Assessment of left ventricular function by nurses is an attractive concept. Recent developments in three dimensional echocardiography coupled with border detection assistance have reduced inter- and intra-observer variability and analysis time. This could allow abbreviated training of nurses to assess cardiac function. A comparative, diagnostic accuracy study evaluating left ventricular ejection fraction assessment utilising a semi-automated, workstation-based protocol performed by echocardiography-naïve nurses on previously acquired three dimensional echocardiography images. Nine cardiac nurses underwent two brief lectures about cardiac anatomy, physiology and three dimensional left ventricular ejection fraction assessment, before a hands-on demonstration in 20 cases. We then selected 50 cases from our three dimensional echocardiography library based on optimal image quality with a broad range of left ventricular ejection fractions, which was quantified by two experienced sonographers and the average used as the comparator for the nurses. Nurses independently measured three dimensional left ventricular ejection fraction using the Auto lvq package with semi-automated border detection. The left ventricular ejection fraction range was 25-72% (70% with a left ventricular ejection fraction <55%). All nurses showed excellent agreement with the sonographers. Minimal intra-observer variability was noted on both short-term (same day) and long-term (>2 weeks later) retest. It is feasible to train nurses to measure left ventricular ejection fraction utilising a semi-automated, workstation-based protocol on previously acquired three dimensional echocardiography images. Further study is needed to determine the feasibility of training nurses to acquire three dimensional echocardiography images on real-world patients to measure left ventricular ejection fraction. Nurse-performed evaluation of left ventricular function could facilitate the broader application of echocardiography to allow cost-effective screening and monitoring for left ventricular dysfunction in high-risk populations. © 2014 John Wiley & Sons Ltd.

Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery.

PubMed

Wijeysundera, Duminda N; Pearse, Rupert M; Shulman, Mark A; Abbott, Tom E F; Torres, Elizabeth; Croal, Bernard L; Granton, John T; Thorpe, Kevin E; Grocott, Michael P W; Farrington, Catherine; Myles, Paul S; Cuthbertson, Brian H

2016-03-11

Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors' subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia. The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1 year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30 days after surgery, and the secondary outcome is all-cause death within 1 year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration. The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Age-specific associations between cardiac vagal activity and functional somatic symptoms: a population-based study.

PubMed

Tak, Lineke M; Janssens, Karin A M; Dietrich, Andrea; Slaets, Joris P J; Rosmalen, Judith G M

2010-01-01

Functional somatic symptoms (FSS) are symptoms not explained by underlying organic pathology. It has frequently been suggested that dysfunction of the autonomic nervous system (ANS) contributes to the development of FSS. We hypothesized that decreased cardiac vagal activity is cross-sectionally and prospectively associated with the number of FSS in the general population. This study was performed in a population-based cohort of 774 adults (45.1% male, mean age +/- SD 53.5 +/- 10.7 years). Participants completed the somatization section of the Composite International Diagnostic Interview surveying the presence of 43 FSS. ANS function was assessed by spectral analysis of heart rate variability in the high-frequency band (HRV-HF), reflecting cardiac vagal activity. Follow-up measurements of HRV-HF and FSS were performed approximately 2 years later. Linear regression analyses, with adjustments for gender, age, body mass index, anxiety, depression, smoking, alcohol use, and frequency of exercise, revealed an interaction of cardiac vagal activity with age: HRV-HF was negatively associated with FSS in adults 52 years (beta = 0.13, t = 2.51, p = 0.012). Longitudinal analysis demonstrated a similar pattern. Decreased cardiac vagal activity is associated with a higher number of FSS in adults aged 52 years needs further exploration. The role of age should be acknowledged in future studies on ANS function in the etiology of FSS. (c) 2010 S. Karger AG, Basel.

Embryonic stem cell grafting in normal and infarcted myocardium: serial assessment with MR imaging and PET dual detection.

PubMed

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

2009-03-01

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. 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. ESCs survived and underwent proliferation in the infarcted and normal hearts, as demonstrated by serial increases in 9-(4-[(18)F]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%. Dual-modality imaging permits complementary information in regard to cell survival and proliferation, graft formation, and effects on cardiac function. http://radiology.rsnajnls.org/cgi/content/full/250/3/821/DC1. RSNA, 2009

Gualou Xiebai Decoction, a Traditional Chinese Medicine, Prevents Cardiac Reperfusion Injury of Hyperlipidemia Rat via Energy Modulation.

PubMed

Yan, Lu-Lu; Zhang, Wei-Yang; Wei, Xiao-Hong; Yan, Li; Pan, Chun-Shui; Yu, Yang; Fan, Jing-Yu; Liu, Yu-Ying; Zhou, Hua; Han, Jing-Yan; Yao, Xin-Sheng

2018-01-01

Background: Gualou Xiebai Decoction (GLXB) is a classic prescription of Chinese medicine used for the treatment of cardiac problems. The present study was designed to explore the effect and mechanism of GLXB on ischemia/reperfusion (I/R) induced disorders in myocardial structure and function, focusing on the regulation of energy metabolism and the RhoA/ROCK pathway. Methods: After hyperlipidemic rat model was established by oral administration of high fat diet, the rats were treated with GLXB for 6 weeks and subjected to 30 min occlusion of the left anterior descending coronary artery (LADCA) followed by 90 min reperfusion to elicit I/R challenge. Myocardial infarct size was assessed by Evans blue-TTC staining. Myocardial blood flow (MBF) and cardiac function were evaluated. Enzyme-linked immunosorbent assay was performed to examine the content of ATP, ADP, AMP, CK, CK-MB, LDH, cTnT, cTnI, and IL-6. Double staining of F-actin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was conducted to assess myocardial apoptosis. Expressions of ATP synthase subunit δ (ATP 5D), and RhoA and ROCK were determined by Western blotting. Results: Administration with GLXB at high dose for 6 weeks protected heart against I/R-induced MBF decrease, myocardial infarction and apoptosis, ameliorated I/R-caused impairment of cardiac function and myocardial structure, restored the decrease in the ratio of ADP/ATP and AMP/ATP, and the expression of ATP 5D with inhibiting the expression of RhoA and ROCK. Conclusions: Treatment with GLXB effectively protects myocardial structure and function from I/R challenge, possibly via regulating energy metabolism involving inactivation of RhoA/ROCK signaling pathway.

Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction: Prevention by the targeted antioxidant MitoQ.

PubMed

Vergeade, Aurélia; Mulder, Paul; Vendeville-Dehaudt, Cathy; Estour, François; Fortin, Dominique; Ventura-Clapier, Renée; Thuillez, Christian; Monteil, Christelle

2010-09-01

The goal of this study was to assess mitochondrial function and ROS production in an experimental model of cocaine-induced cardiac dysfunction. We hypothesized that cocaine abuse may lead to altered mitochondrial function that in turn may cause left ventricular dysfunction. Seven days of cocaine administration to rats led to an increased oxygen consumption detected in cardiac fibers, specifically through complex I and complex III. ROS levels were increased, specifically in interfibrillar mitochondria. In parallel there was a decrease in ATP synthesis, whereas no difference was observed in subsarcolemmal mitochondria. This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine. MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-volume data. Taken together, these results extend previous studies and demonstrate that cocaine-induced cardiac dysfunction may be due to a mitochondrial defect. Copyright 2010 Elsevier Inc. All rights reserved.

Extracorporeal shockwave myocardial revascularization improves clinical symptoms and left ventricular function in patients with refractory angina.

PubMed

Zuozienė, Gitana; Laucevičius, Aleksandras; Leibowitz, David

2012-01-01

Medical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. Patients with Canadian Cardiovascular Society (CCS) class III-IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. Twenty patients (four women, 16 men; mean age 64 years, range 45-83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). This study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.

Moderate intensity exercise prevents diabetic cardiomyopathy associated contractile dysfunction through restoration of mitochondrial function and connexin 43 levels in db/db mice.

PubMed

Veeranki, Sudhakar; Givvimani, Srikanth; Kundu, Sourav; Metreveli, Naira; Pushpakumar, Sathnur; Tyagi, Suresh C

2016-03-01

Although the cardiovascular benefits of exercise are well known, exercise induced effects and mechanisms in prevention of cardiomyopathy are less clear during obesity associated type-2 diabetes. The current study assessed the impact of moderate intensity exercise on diabetic cardiomyopathy by examining cardiac function and structure and mitochondrial function. Obese-diabetic (db/db), and lean control (db/+) mice, were subjected to a 5 week, 300 m run on a tread-mill for 5 days/week at the speeds of 10-11 m/min. Various physiological parameters were recorded and the heart function was evaluated with M-mode echocardiography. Contraction parameters and calcium transits were examined on isolated cardiomyocytes. At the molecular level: connexin 43 and 37 (Cx43 and 37) levels, mitochondrial biogenesis regulators: Mfn2 and Drp-1 levels, mitochondrial trans-membrane potential and cytochrome c leakage were assessed through western blotting immunohistochemistry and flow cytometry. Ability of exercise to reverse oxygen consumption rate (OCR), tissue ATP levels, and cardiac fibrosis were also determined. The exercise regimen was able to prevent diabetic cardiac functional deficiencies: ejection fraction (EF) and fractional shortening (FS). Improvements in contraction velocity and contraction maximum were noted with the isolated cardiomyocytes. Restoration of interstitial and micro-vessels associated Cx43 levels and improved gap junction intercellular communication (GJIC) were observed. The decline in the Mfn2/Drp-1 ratio in the db/db mice hearts was prevented after exercise. The exercise regimen further attenuated transmembrane potential decline and cytochrome c leakage. These corrections further led to improvements in OCR and tissue ATP levels and reduction in cardiac fibrosis. Moderate intensity exercise produced significant cardiovascular benefits by improving mitochondrial function through restoration of Cx43 networks and mitochondrial trans-membrane potential and prevention of excessive mitochondrial fission. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electroencephalographic Recordings During Withdrawal of Life-Sustaining Therapy Until 30 Minutes After Declaration of Death.

PubMed

Norton, Loretta; Gibson, Raechelle M; Gofton, Teneille; Benson, Carolyn; Dhanani, Sonny; Shemie, Sam D; Hornby, Laura; Ward, Roxanne; Young, G Bryan

2017-03-01

The timing of the circulatory determination of death for organ donation presents a medical and ethical challenge. Concerns have been raised about the timing of electrocerebral inactivity in relation to the cessation of circulatory function in organ donation after cardio-circulatory death. Nonprocessed electroencephalographic (EEG) measures have not been characterized and may provide insight into neurological function during this process. We assessed electrocortical data in relation to cardiac function after withdrawal of life-sustaining therapy and in the postmortem period after cardiac arrest for four patients in a Canadian intensive care unit. Subhairline EEG and cardio-circulatory monitoring including electrocardiogram, arterial blood pressure (ABP), and oxygen saturation were captured. Electrocerebral inactivity preceded the cessation of the cardiac rhythm and ABP in three patients. In one patient, single delta wave bursts persisted following the cessation of both the cardiac rhythm and ABP. There was a significant difference in EEG amplitude between the 30-minute period before and the 5-minute period following ABP cessation for the group, but we did not observe any well-defined EEG states following the early cardiac arrest period. In a case series of four patients, EEG inactivity preceded electrocardiogram and ABP inactivity during the dying process in three patients. Further study of the electroencephalogram during the withdrawal of life sustaining therapies will add clarity to medical, ethical, and legal concerns for donation after circulatory determined death.

The six-minute walk test in patients with AL amyloidosis: a single centre case series.

PubMed

Pulido, Vina; Doros, Gheorghe; Berk, John L; Sanchorawala, Vaishali

2017-05-01

The six-minute walk test (6MWT) has been widely used as an objective evaluation of functional exercise capacity and response to medical intervention in cardiopulmonary diseases. However, little is known about the 6MWT in evaluating patients with AL amyloidosis. We performed a retrospective study of 120 adults with systemic AL amyloidosis (60 with cardiac involvement and 60 without cardiac involvement) who had their initial evaluation at the Amyloidosis Center between 2013 and 2015 and had undergone 6MWT as a measure of functional exercise capacity. Forty-seven patients with cardiac involvement and 41 patients without cardiac involvement were included in the final analysis. The six-minute walk distances (6MWD) were 368 ± 105 m and 420 ± 116 m (mean ± SD), respectively (P = 0·03). Among AL amyloidosis patients with cardiac involvement, the 6MWD was associated with New York Heart Association class (P < 0·001), B-type natriuretic peptide (P = 0·003) and overall survival (hazard ratio 0·381, 95% confidence interval 0·215-0·676, P = 0·001). In conclusion, the 6MWT is a valuable tool in assessing functional exercise capacity in patients with AL amyloidosis. © 2017 John Wiley & Sons Ltd.

Genome-wide compendium and functional assessment of in vivo heart enhancers

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

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of > 35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of > 80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs ofmore » two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.« less

Genome-wide compendium and functional assessment of in vivo heart enhancers

DOE PAGES

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; ...

2016-10-05

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of > 35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of > 80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs ofmore » two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.« less

Genome-wide compendium and functional assessment of in vivo heart enhancers

PubMed Central

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; Fukuda-Yuzawa, Yoko; Osterwalder, Marco; Mannion, Brandon J.; May, Dalit; Spurrell, Cailyn H.; Plajzer-Frick, Ingrid; Pickle, Catherine S.; Lee, Elizabeth; Garvin, Tyler H.; Kato, Momoe; Akiyama, Jennifer A.; Afzal, Veena; Lee, Ah Young; Gorkin, David U.; Ren, Bing; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

2016-01-01

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs of two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function. PMID:27703156

Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

NASA Astrophysics Data System (ADS)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction.

PubMed

van Hout, Gerardus P J; Bosch, Lena; Ellenbroek, Guilielmus H J M; de Haan, Judith J; van Solinge, Wouter W; Cooper, Matthew A; Arslan, Fatih; de Jager, Saskia C A; Robertson, Avril A B; Pasterkamp, Gerard; Hoefer, Imo E

2017-03-14

Myocardial infarction (MI) triggers an intense inflammatory response that is associated with infarct expansion and is detrimental for cardiac function. Interleukin (IL)-1β and IL-18 are key players in this response and are controlled by the NLRP3-inflammasome. In the current study, we therefore hypothesized that selective inhibition of the NLRP3-inflammasome reduces infarct size and preserves cardiac function in a porcine MI model. Thirty female landrace pigs were subjected to 75 min transluminal balloon occlusion and treated with the NLRP3-inflammasome inhibitor MCC950 (6 or 3 mg/kg) or placebo for 7 days in a randomized, blinded fashion. After 7 days, 3D-echocardiography was performed to assess cardiac function and Evans blue/TTC double staining was executed to assess the area at risk (AAR) and infarct size (IS). The IS/AAR was lower in the 6 mg/kg group (64.6 ± 8.8%, P = 0.004) and 3 mg/kg group (69.7 ± 7.2%, P = 0.038) compared with the control group (77.5 ± 6.3%). MCC950 treatment markedly preserved left ventricular ejection fraction in treated animals (6 mg/kg 47 ± 8%, P = 0.001; 3 mg/kg 45 ± 7%, P = 0.031; control 37 ± 6%). Myocardial neutrophil influx was attenuated in treated compared with non-treated animals (6 mg/kg 132 ± 72 neutrophils/mm2, P = 0.035; 3 mg/kg 207 ± 210 neutrophils/mm2, P = 0.5; control 266 ± 158 neutrophils/mm2). Myocardial IL-1β levels were dose-dependently reduced in treated animals. NLRP3-inflammasome inhibition reduces infarct size and preserves cardiac function in a randomized, blinded translational large animal MI model. Hence, NLRP3-inflammasome inhibition may have therapeutic potential in acute MI patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Validation of Pre-operative Patient Self-Assessment of Cardiac Risk for Non-Cardiac Surgery: Foundations for Decision Support

PubMed Central

Manaktala, Sharad; Rockwood, Todd; Adam, Terrence J.

2013-01-01

Objectives: To better characterize patient understanding of their risk of cardiac complications from non-cardiac surgery and to develop a patient driven clinical decision support system for preoperative patient risk management. Methods: A patient-driven preoperative self-assessment decision support tool for perioperative assessment was created. Patient’ self-perception of cardiac risk and self-report data for risk factors were compared with gold standard preoperative physician assessment to evaluate agreement. Results: The patient generated cardiac risk profile was used for risk score generation and had excellent agreement with the expert physician assessment. However, patient subjective self-perception risk of cardiovascular complications had poor agreement with expert assessment. Conclusion: A patient driven cardiac risk assessment tool provides a high degree of agreement with expert provider assessment demonstrating clinical feasibility. The limited agreement between provider risk assessment and patient self-perception underscores a need for further work including focused preoperative patient education on cardiac risk. PMID:24551384

Computer-based assessment of right ventricular regional ejection fraction in patients with repaired Tetralogy of Fallot

NASA Astrophysics Data System (ADS)

Teo, S.-K.; Wong, S. T.; Tan, M. L.; Su, Y.; Zhong, L.; Tan, Ru-San

2015-03-01

After surgical repair for Tetralogy of Fallot (TOF), most patients experience long-term complications as the right ventricle (RV) undergoes progressive remodeling that eventually affect heart functions. Thus, post-repair surgery is required to prevent further deterioration of RV functions that may result in malignant ventricular arrhythmias and mortality. The timing of such post-repair surgery therefore depends crucially on the quantitative assessment of the RV functions. Current clinical indices for such functional assessment measure global properties such as RV volumes and ejection fraction. However, these indices are less than ideal as regional variations and anomalies are obscured. Therefore, we sought to (i) develop a quantitative method to assess RV regional function using regional ejection fraction (REF) based on a 13-segment model, and (ii) evaluate the effectiveness of REF in discriminating 6 repaired TOF patients and 6 normal control based on cardiac magnetic resonance (CMR) imaging. We observed that the REF for the individual segments in the patient group is significantly lower compared to the control group (P < 0.05 using a 2-tail student t-test). In addition, we also observed that the aggregated REF at the basal, mid-cavity and apical regions for the patient group is significantly lower compared to the control group (P < 0.001 using a 2-tail student t-test). The results suggest that REF could potentially be used as a quantitative index for assessing RV regional functions. The computational time per data set is approximately 60 seconds, which demonstrates our method's clinical potential as a real-time cardiac assessment tool.

Optimized Heart Sampling and Systematic Evaluation of Cardiac Therapies in Mouse Models of Ischemic Injury: Assessment of Cardiac Remodeling and Semi-Automated Quantification of Myocardial Infarct Size.

PubMed

Valente, Mariana; Araújo, Ana; Esteves, Tiago; Laundos, Tiago L; Freire, Ana G; Quelhas, Pedro; Pinto-do-Ó, Perpétua; Nascimento, Diana S

2015-12-02

Cardiac therapies are commonly tested preclinically in small-animal models of myocardial infarction. Following functional evaluation, post-mortem histological analysis is essential to assess morphological and molecular alterations underlying the effectiveness of treatment. However, non-methodical and inadequate sampling of the left ventricle often leads to misinterpretations and variability, making direct study comparisons unreliable. Protocols are provided for representative sampling of the ischemic mouse heart followed by morphometric analysis of the left ventricle. Extending the use of this sampling to other types of in situ analysis is also illustrated through the assessment of neovascularization and cellular engraftment in a cell-based therapy setting. This is of interest to the general cardiovascular research community as it details methods for standardization and simplification of histo-morphometric evaluation of emergent heart therapies. © 2015 by John Wiley & Sons, Inc. Copyright © 2015 John Wiley & Sons, Inc.

Thrombolytic-Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest.

PubMed

Spinelli, Elena; Davis, Ryan P; Ren, Xiaodan; Sheth, Parth S; Tooley, Trevor R; Iyengar, Amit; Sowell, Brandon; Owens, Gabe E; Bocks, Martin L; Jacobs, Teresa L; Yang, Lynda J; Stacey, William C; Bartlett, Robert H; Rojas-Peña, Alvaro; Neumar, Robert W

2016-02-01

To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest. Laboratory investigation. University laboratory. Pigs. Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation. A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages. In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.

Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature.

PubMed

Maagaard, Marie; Heiberg, Johan

2016-09-01

Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3-168 patients, mean age-ranges of 5-33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22-34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O 2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac function should be integrated in the clinical assessment of patients with PE.

Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature

PubMed Central

Heiberg, Johan

2016-01-01

Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3–168 patients, mean age-ranges of 5–33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22–34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac function should be integrated in the clinical assessment of patients with PE. PMID:27747182

Geraniol alleviates diabetic cardiac complications: Effect on cardiac ischemia and oxidative stress.

PubMed

El-Bassossy, Hany M; Ghaleb, Hanna; Elberry, Ahmed A; Balamash, Khadijah S; Ghareib, Salah A; Azhar, Ahmad; Banjar, Zainy

2017-04-01

The present study was planned to assess the possible protective effect of geraniol on cardiovascular complications in an animal model with diabetes. Diabetes was induced in rats by a single streptozotocin injection. In the treated group, geraniol (150mgkg -1 day -1 ) was administered orally starting from the 15th day after induction of diabetes, and ending after 7 weeks; diabetic control rats were given vehicle for the same period. At the end of the study, cardiac contractility was assessed by using a Millar microtip catheter in anesthetised rats, and cardiac conductivity determined by a surface ECG. Serum levels of glucose, cholesterol, triglyceride and adiponectin as well as urine 8-isoprostane were determined. In addition, cardiac superoxide dismutase (SOD) and catalase activity were measured. Geraniol administration significantly alleviated the attenuated cardiac systolic function associated with diabetes as indicated by inhibiting the decrease in the rate of rise (dP/dt max ) in ventricular pressure and the increase in systolic duration observed in diabetic rats. In addition, geraniol alleviated impaired diastolic function as shown by inhibiting the decrease in the rate of fall (dP/dt min ) in ventricular pressure and increased isovolumic relaxation constant (Tau) observed in diabetic rats. ECG recordings showed that geraniol prevented any increase in QTc and T-peak-T-end intervals, and markers of LV ischemia and arrhythmogenesis, seen in diabetic animals. Geraniol suppressed the exaggerated oxidative stress as evidenced by preventing the increase in 8-isoprotane. In diabetic heart tissue, geraniol prevented the inhibition in catalase activity but did not affect the heart SOD. Geraniol partially reduced hyperglycemia, prevented the hypercholesterolemia, but did not affect the serum level of adiponectin in diabetic animals. Results obtained in this study suggest that geraniol provides a potent protective effect against cardiac dysfunction induced by diabetes. This ameliorative effect could be attributed to its suppression of oxidative stress. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Non-invasive assessment of low- and intermediate-risk patients with chest pain

PubMed Central

Balfour, Pelbreton C.; Gonzalez, Jorge A.; Kramer, Christopher M.

2016-01-01

Coronary artery disease (CAD) remains a significant global public health burden despite advancements in prevention and therapeutic strategies. Common non-invasive imaging modalities, anatomic and functional, are available for the assessment of patients with stable chest pain. Exercise electrocardiography is a long-standing method for evaluation for CAD and remains the initial test for the majority of patients who can exercise adequately with a baseline interpretable electrocardiogram. The addition of cardiac imaging to exercise testing provides incremental benefit for accurate diagnosis for CAD and is particularly useful in patients who are unable to exercise adequately and/or have uninterpretable electrocardiograms. Radionuclide myocardial perfusion imaging and echocardiography with exercise or pharmacological stress provide high sensitivity and specificity in the detection and further risk stratification of patients with CAD. Recently, coronary computed tomography angiography has demonstrated its growing role to rule out significant CAD given its high negative predictive value. Although less available, stress cardiac magnetic resonance provides a comprehensive assessment of cardiac structure and function and provides a high diagnostic accuracy in the detection of CAD. The utilization of non-invasive testing is complex due to various advantages and limitations, particularly in the assessment of low- and intermediate-risk patients with chest pain, where no single study is suitable for all patients. This review will describe currently available non-invasive modalities, along with current evidence-based guidelines and appropriate use criteria in the assessment of low- and intermediate-risk patients with suspected, stable CAD. PMID:27717538

Large Cardiac Muscle Patches Engineered From Human Induced-Pluripotent Stem Cell-Derived Cardiac Cells Improve Recovery From Myocardial Infarction in Swine.

PubMed

Gao, Ling; Gregorich, Zachery R; Zhu, Wuqiang; Mattapally, Saidulu; Oduk, Yasin; Lou, Xi; Kannappan, Ramaswamy; Borovjagin, Anton V; Walcott, Gregory P; Pollard, Andrew E; Fast, Vladimir G; Hu, Xinyang; Lloyd, Steven G; Ge, Ying; Zhang, Jianyi

2018-04-17

Here, we generated human cardiac muscle patches (hCMPs) of clinically relevant dimensions (4 cm × 2 cm × 1.25 mm) by suspending cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human induced-pluripotent stem cells in a fibrin scaffold and then culturing the construct on a dynamic (rocking) platform. In vitro assessments of hCMPs suggest maturation in response to dynamic culture stimulation. In vivo assessments were conducted in a porcine model of myocardial infarction (MI). Animal groups included: MI hearts treated with 2 hCMPs (MI+hCMP, n=13), MI hearts treated with 2 cell-free open fibrin patches (n=14), or MI hearts with neither experimental patch (n=15); a fourth group of animals underwent sham surgery (Sham, n=8). Cardiac function and infarct size were evaluated by MRI, arrhythmia incidence by implanted loop recorders, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Additional studies examined the myocardial protein expression profile changes and potential mechanisms of action that related to exosomes from the cell patch. The hCMPs began to beat synchronously within 1 day of fabrication, and after 7 days of dynamic culture stimulation, in vitro assessments indicated the mechanisms related to the improvements in electronic mechanical coupling, calcium-handling, and force generation, suggesting a maturation process during the dynamic culture. The engraftment rate was 10.9±1.8% at 4 weeks after the transplantation. The hCMP transplantation was associated with significant improvements in left ventricular function, infarct size, myocardial wall stress, myocardial hypertrophy, and reduced apoptosis in the periscar boarder zone myocardium. hCMP transplantation also reversed some MI-associated changes in sarcomeric regulatory protein phosphorylation. The exosomes released from the hCMP appeared to have cytoprotective properties that improved cardiomyocyte survival. We have fabricated a clinically relevant size of hCMP with trilineage cardiac cells derived from human induced-pluripotent stem cells. The hCMP matures in vitro during 7 days of dynamic culture. Transplantation of this type of hCMP results in significantly reduced infarct size and improvements in cardiac function that are associated with reduction in left ventricular wall stress. The hCMP treatment is not associated with significant changes in arrhythmogenicity. © 2017 American Heart Association, Inc.

Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension.

PubMed

van Brussel, Peter M; Eeftinck Schattenkerk, Daan W; Dobrowolski, Linn C; de Winter, Robbert J; Reekers, Jim A; Verberne, Hein J; Vogt, Liffert; van den Born, Bert-Jan H

2016-01-01

Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity and cardiovascular parameters. A total of 21 consecutive patients with refractory hypertension (daytime ambulatory blood pressure (BP)≥150/100 mmHg despite the use of 3 or more antihypertensive drugs), no evidence for secondary hypertension and normal renovascular anatomy were included. RSD was performed with the Medtronic Symplicity renal denervation catheter with an average of 4.2 (range 3-6) ablations per renal artery. To assess cardiac sympathetic activity, 123I-mIBG cardiac scintigraphy was performed before and 6 weeks after. In addition, the effect of RSD on peripheral BP and cardiac hemodynamics were assessed non-invasively. 123I-mIBG uptake before and after RSD was 1.7±0.4% vs. 1.7±0.5% at 15 min. and 1.4±0.4% vs. 1.5±0.5% after 4 h. As a consequence, washout rate was similar before (33.7±11.7%) and after RSD (30.1±12.6%, p=0.27). In line with earlier RSD studies, a significant drop in systolic office BP (-12.2 mmHg, p=0.04) was detected, whereas the decrease in ambulatory BP was not significant. No changes were seen in heart rate, stroke volume or left ventricular contractility, both in supine position and after standing. In concert with previous reports, RSD leads to a significant drop in office BP. However, a reduction in sympathetic activity could not be demonstrated on a cardiac level. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials.

PubMed

Holubkov, Richard; Clark, Amy E; Moler, Frank W; Slomine, Beth S; Christensen, James R; Silverstein, Faye S; Meert, Kathleen L; Pollack, Murray M; Dean, J Michael

2015-01-01

The Therapeutic Hypothermia After Pediatric Cardiac Arrest trials will determine whether therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition, in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during Therapeutic Hypothermia After Pediatric Cardiac Arrest protocol development. Consensus assessment of potential outcomes and evaluation timepoints. None. We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. Twelve months after arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in Vineland Adaptive Behavior Scales Second Edition from prearrest level, measured as quasicontinuous with death and vegetative status being worst-possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes because of easier interpretability and favored outcomes based solely on postarrest status because of concerns about accurate parental assessment of prearrest status and differing clinical impact of a given Vineland Adaptive Behavior Scales Second Edition change depending on prearrest status. Simulations found only modest power loss from categorizing or dichotomizing quasicontinuous outcomes because of high expected mortality. The primary outcome selected was survival with 12-month Vineland Adaptive Behavior Scales Second Edition no less than two SD below a reference population mean (70 points), necessarily evaluated only among children with prearrest Vineland Adaptive Behavior Scales Second Edition greater than or equal to 70. Two secondary efficacy outcomes, 12-month survival and quasicontinuous Vineland Adaptive Behavior Scales Second Edition change from prearrest level, will be evaluated among all randomized children, including those with compromised function prearrest. Extensive discussion of optimal efficacy assessment timing, and of the advantages versus drawbacks of incorporating prearrest status and using quasicontinuous versus simpler outcomes, was highly beneficial to the final Therapeutic Hypothermia After Pediatric Cardiac Arrest design. A relatively simple, binary primary outcome evaluated at 12 months was selected, with two secondary outcomes that address the potential disadvantages of primary outcome.

The Role of CMR in Cardiomyopathies

PubMed Central

Kramer, Christopher M.

2015-01-01

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

Right ventricular functional analysis utilizing first pass radionuclide angiography for pre-operative ventricular assist device planning: a multi-modality comparison.

PubMed

Avery, Ryan; Day, Kevin; Jokerst, Clinton; Kazui, Toshinobu; Krupinski, Elizabeth; Khalpey, Zain

2017-10-10

Advanced heart failure treated with a left ventricular assist device is associated with a higher risk of right heart failure. Many advanced heart failures patients are treated with an ICD, a relative contraindication to MRI, prior to assist device placement. Given this limitation, left and right ventricular function for patients with an ICD is calculated using radionuclide angiography utilizing planar multigated acquisition (MUGA) and first pass radionuclide angiography (FPRNA), respectively. Given the availability of MRI protocols that can accommodate patients with ICDs, we have correlated the findings of ventricular functional analysis using radionuclide angiography to cardiac MRI, the reference standard for ventricle function calculation, to directly correlate calculated ejection fractions between these modalities, and to also assess agreement between available echocardiographic and hemodynamic parameters of right ventricular function. A retrospective review from January 2012 through May 2014 was performed to identify advanced heart failure patients who underwent both cardiac MRI and radionuclide angiography for ventricular functional analysis. Nine heart failure patients (8 men, 1 woman; mean age of 57.0 years) were identified. The average time between the cardiac MRI and radionuclide angiography exams was 38.9 days (range: 1 - 119 days). All patients undergoing cardiac MRI were scanned using an institutionally approved protocol for ICD with no device-related complications identified. A retrospective chart review of each patient for cardiomyopathy diagnosis, clinical follow-up, and echocardiogram and right heart catheterization performed during evaluation was also performed. The 9 patients demonstrated a mean left ventricular ejection fraction (LVEF) using cardiac MRI of 20.7% (12 - 40%). Mean LVEF using MUGA was 22.6% (12 - 49%). The mean right ventricular ejection fraction (RVEF) utilizing cardiac MRI was 28.3% (16 - 43%), and the mean RVEF calculated by FPRNA was 32.6% (9 - 56%). The mean discrepancy for LVEF between cardiac MRI and MUGA was 4.1% (0 - 9%), and correlation of calculated LVEF using cardiac MRI and MUGA demonstrated an R of 0.9. The mean discrepancy for RVEF between cardiac MRI and FPRNA was 12.0% (range: 2 - 24%) with a moderate correlation (R = 0.5). The increased discrepancies for RV analysis were statistically significant using an unpaired t-test (t = 3.19, p = 0.0061). Echocardiogram parameters of RV function, including TAPSE and FAC, were for available for all 9 patients and agreement with cardiac MRI demonstrated a kappa statistic for TAPSE of 0.39 (95% CI of 0.06 - 0.72) and for FAC of 0.64 (95% of 0.21 - 1.00). Heart failure patients are increasingly requiring left ventricular assist device placement; however, definitive evaluation of biventricular function is required due to the increased mortality rate associated with right heart failure after assist device placement. Our results suggest that FPRNA only has a moderate correlation with reference standard RVEFs calculated using cardiac MRI, which was similar to calculated agreements between cardiac MRI and echocardiographic parameters of right ventricular function. Given the need for identification of patients at risk for right heart failure, further studies are warranted to determine a more accurate estimate of RVEF for heart failure patients during pre-operative ventricular assist device planning.

Heart repair by reprogramming non-myocytes with cardiac transcription factors

PubMed Central

Song, Kunhua; Nam, Young-Jae; Luo, Xiang; Qi, Xiaoxia; Tan, Wei; Huang, Guo N.; Acharya, Asha; Smith, Christopher L.; Tallquist, Michelle D.; Neilson, Eric G.; Hill, Joseph A.; Bassel-Duby, Rhonda; Olson, Eric N.

2012-01-01

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodeling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, Hand2, MEF2C and Tbx5 can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodeling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules. PMID:22660318

Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.

PubMed

Schulte, Astrid; Lichtenstern, Christoph; Henrich, Michael; Weigand, Markus A; Uhle, Florian

2014-05-15

During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function. We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion. Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock. Copyright © 2014 Elsevier Inc. All rights reserved.

Pulmonary Catherization Data Correlate Poorly with Renal Function in Heart Failure.

PubMed

Masha, Luke; Stone, James; Stone, Danielle; Zhang, Jun; Sheng, Luo

2018-04-10

The mechanisms of renal dysfunction in heart failure are poorly understood. We chose to explore the relationship of cardiac filling pressures and cardiac index (CI) in relation to renal dysfunction in advanced heart failure. To determine the relationship between renal function and cardiac filling pressures using the United Network of Organ Sharing (UNOS) pulmonary artery catherization registry. Patients over the age of 18 years who were listed for single-organ heart transplantation were included. Exclusion criteria included a history of mechanical circulatory support, previous transplantation, any use of renal replacement therapy, prior history of malignancy, and cardiac surgery, amongst others. Correlations between serum creatinine (SCr) and CI, pulmonary capillary wedge pressure (PCWP), pulmonary artery systolic pressure (PASP), and pulmonary artery diastolic pressure (PADP) were assessed by Pearson correlation coefficients and simple linear regression coefficients. Pearson correlation coefficients between SCr and PCWP, PASP, and PADP were near zero with values of 0.1, 0.07, and 0.08, respectively (p < 0.0001). A weak negative correlation coefficient between SCr and CI was found (correlation coefficient, -0.045, p = 0.027). In a subgroup of young patients unlikely to have noncardiac etiologies, no significant correlations between these values were identified. These findings suggest that, as assessed by pulmonary artery catherization, none of the factors - PCWP, PASP, PADP, or CI - play a prominent role in cardiorenal syndromes. © 2018 S. Karger AG, Basel.

Multi-Physics MRI-Based Two-Layer Fluid-Structure Interaction Anisotropic Models of Human Right and Left Ventricles with Different Patch Materials: Cardiac Function Assessment and Mechanical Stress Analysis

PubMed Central

Tang, Dalin; Yang, Chun; Geva, Tal; Gaudette, Glenn; del Nido, Pedro J.

2011-01-01

Multi-physics right and left ventricle (RV/LV) fluid-structure interaction (FSI) models were introduced to perform mechanical stress analysis and evaluate the effect of patch materials on RV function. The FSI models included three different patch materials (Dacron scaffold, treated pericardium, and contracting myocardium), two-layer construction, fiber orientation, and active anisotropic material properties. The models were constructed based on cardiac magnetic resonance (CMR) images acquired from a patient with severe RV dilatation and solved by ADINA. Our results indicate that the patch model with contracting myocardium leads to decreased stress level in the patch area, improved RV function and patch area contractility. PMID:21765559

The successful implantation of continuous-flow left ventricular assist device as a destination therapy in Korea: echocardiographic assessment.

PubMed

Lee, Ga Yeon; Park, Sung-Ji; Kim, Sujin; Choi, Namgyung; Jeong, Dong Seop; Jeon, Eun-Seok; Lee, Young Tak

2014-01-01

Left ventricular assist device (LVAD) is a good treatment option for the patients ineligible for cardiac transplantation. Several studies have demonstrated that a ventricular assist device improves the quality of life and prognosis of the patients with end-stage heart failure. A 75-yr-old man debilitated with New York Heart Association (NYHA) functional class III-IV due to severe left ventricular systolic dysfunction received LVAD implantation as a destination therapy. The patient was discharged with improved functional status (NYHA functional class II) after appropriate cardiac rehabilitation and education about how to manage the device and potential emergency situations. This is the first case of successful continuous-flow LVAD implantation as a destination therapy in Korea.

Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality

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

Xia, Congying; Dong, Ruolan; Chen, Chen

Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejectionmore » fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling. - Highlights: • ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction. • ACOT1 can regulate PPARa/PGC1a signaling pathway. • We first generate the transgenic mice with cardiomyocyte specific expression of ACOT1.« less

Assessment of left atrial volume and function: a comparative study between echocardiography, magnetic resonance imaging and multi slice computed tomography.

PubMed

Kühl, J Tobias; Lønborg, Jacob; Fuchs, Andreas; Andersen, Mads J; Vejlstrup, Niels; Kelbæk, Henning; Engstrøm, Thomas; Møller, Jacob E; Kofoed, Klaus F

2012-06-01

Measurement of left atrial (LA) maximal volume (LA(max)) using two-dimensional transthoracic echocardiography (TTE) provides prognostic information in several cardiac diseases. However, the relationship between LA(max) and LA function is poorly understood and TTE is less well suited for measuring dynamic LA volume changes. Conversely, cardiac magnetic resonance imaging (CMR) and multi-slice computed tomography (MSCT) appears more appropriate for such measures. We sought to determine the relationship between LA size assessed with TTE and LA size and function assessed with CMR and MSCT. Fifty-four patients were examined 3 months post myocardial infarction with echocardiography, CMR and MSCT. Left atrial volumes and LA reservoir function were assessed by TTE. LA time-volume curves were determined and LA reservoir function (cyclic change and fractional change), passive emptying function (reservoir volume) and pump function (left atrial ejection fraction-LAEF) were derived using CMR and MSCT. Left atrial fractional change and left atrial ejection fraction (LAEF) determined with CMR and MSCT were unrelated to LA(max) enlargement by echocardiography (P = NS). There was an overall good agreement between CMR and MSCT, with a small to moderate bias in LA(max) (4.9 ± 10.4 ml), CC (3.1 ± 9.1 ml) and reservoir volume (3.4 ± 9.1 ml). TTE underestimates LA(max) with up to 32% compared with CMR and MSCT (P < 0.001). Left atrial function assessed with MSCT and CMR as LA fractional change and LAEF is not significantly related to LA(max) measured by TTE. TTE systematically underestimated LA volumes, whereas there are good agreements between MSCT and CMR for volumetric and functional properties.

Cardiac iron load and function in transfused patients treated with deferasirox (the MILE study).

PubMed

Ho, P Joy; Tay, Lay; Teo, Juliana; Marlton, Paula; Grigg, Andrew; St Pierre, Tim; Brown, Greg; Badcock, Caro-Anne; Traficante, Robert; Gervasio, Othon L; Bowden, Donald K

2017-02-01

To assess the effect of iron chelation therapy with deferasirox on cardiac iron and function in patients with transfusion-dependent thalassemia major, sickle cell disease (SCD), and myelodysplastic syndromes (MDS). This phase IV, single-arm, open-label study over 53 wk evaluated the change in cardiac and liver iron load with deferasirox (up to 40 mg/kg/d), measured by magnetic resonance imaging (MRI). Cardiac iron load (myocardial T2*) significantly improved (P = 0.002) overall (n = 46; n = 36 thalassemia major, n = 4 SCD, n = 6 MDS). Results were significant for patients with normal and moderate baseline cardiac iron (P = 0.017 and P = 0.015, respectively), but not in the five patients with severe cardiac iron load. Liver iron concentration (LIC) significantly decreased overall [mean LIC 10.4 to 8.2 mg Fe/g dry tissue (dw); P = 0.024], particularly in those with baseline LIC >7 mg Fe/g dw (19.9 to 15.6 mg Fe/g dw; P = 0.002). Furthermore, myocardial T2* significantly increased in patients with LIC <7 mg Fe/g dw, but not in those with a higher LIC. Safety was consistent with previous reports. Once-daily deferasirox over 1 yr significantly increased myocardial T2* and reduced LIC. This confirms that single-agent deferasirox is effective in the management of cardiac iron, especially for patients with myocardial T2* >10 ms (Clinicaltrials.gov identifier: NCT00673608). © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cardiac gene transfer of short hairpin RNA directed against phospholamban effectively knocks down gene expression but causes cellular toxicity in canines.

PubMed

Bish, Lawrence T; Sleeper, Meg M; Reynolds, Caryn; Gazzara, Jeffrey; Withnall, Elanor; Singletary, Gretchen E; Buchlis, George; Hui, Daniel; High, Katherine A; Gao, Guangping; Wilson, James M; Sweeney, H Lee

2011-08-01

Derangements in calcium cycling have been described in failing hearts, and preclinical studies have suggested that therapies aimed at correcting this defect can lead to improvements in cardiac function and survival. One strategy to improve calcium cycling would be to inhibit phospholamban (PLB), the negative regulator of SERCA2a that is upregulated in failing hearts. The goal of this study was to evaluate the safety and efficacy of using adeno-associated virus (AAV)-mediated cardiac gene transfer of short hairpin RNA (shRNA) to knock down expression of PLB. Six dogs were treated with self-complementary AAV serotype 6 (scAAV6) expressing shRNA against PLB. Three control dogs were treated with empty AAV6 capsid, and two control dogs were treated with scAAV6 expressing dominant negative PLB. Vector was delivered via a percutaneously inserted cardiac injection catheter. PLB mRNA and protein expression were analyzed in three of six shRNA dogs between days 16 and 26. The other three shRNA dogs and five control dogs were monitored long-term to assess cardiac safety. PLB mRNA was reduced 16-fold, and PLB protein was reduced 5-fold, with treatment. Serum troponin elevation and depressed cardiac function were observed in the shRNA group only at 4 weeks. An enzyme-linked immunospot assay failed to detect any T cells reactive to AAV6 capsid in peripheral blood mononuclear cells, heart, or spleen. Microarray analysis revealed alterations in cardiac expression of several microRNAs with shRNA treatment. AAV6-mediated cardiac gene transfer of shRNA effectively knocks down PLB expression but is associated with severe cardiac toxicity. Toxicity may result from dysregulation of endogenous microRNA pathways.

Functional Cardiac Recovery and Hematologic Response to Chemotherapy in Patients With Light-Chain Amyloidosis (from the Stanford University Amyloidosis Registry).

PubMed

Tuzovic, Mirela; Kobayashi, Yukari; Wheeler, Matthew; Barrett, Christopher; Liedtke, Michaela; Lafayette, Richard; Schrier, Stanley; Haddad, Francois; Witteles, Ronald

2017-10-15

Cardiac involvement is common in patients with light-chain (AL) amyloidosis and portends a poor prognosis, although little is known about the changes in cardiac mechanics after chemotherapy. We sought to explore the relation between amyloidosis staging and baseline cardiac mechanics and to investigate short-term changes in cardiac mechanics after chemotherapy. We identified 41 consecutive patients from the Stanford Amyloid Center who had echocardiograms and free light-chain values before and after chemotherapy, along with 40 age- and gender-matched controls. Echocardiographic assessment included left ventricular global longitudinal strain, E/e' ratio, and left atrial (LA) stiffness. Hematologic response to chemotherapy was defined as ≥50% reduction in the difference between the involved and the uninvolved free light chain (dFLC). The mean age was 66.9 ± 8.4 years and 66% were men. Before chemotherapy, global longitudinal strain, E/e' ratio, and LA stiffness were impaired in patients with amyloidosis compared with controls, and the severity of impairment worsened with advanced staging. After chemotherapy, hematologic response was observed in 30 (73%) patients. There was a significant association between the change in dFLC and cardiac function (E/e' ratio: r = -0.43, p = 0.01; LA stiffness: r = -0.35, p = 0.05). There was no significant improvement in cardiac mechanics in patients without a hematologic response to chemotherapy. In conclusion, amyloidosis stage correlated with noninvasive measurements of cardiac mechanics, and improvement in dFLC correlated with cardiac improvement on short-term follow-up echocardiography. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiac Gene Transfer of Short Hairpin RNA Directed Against Phospholamban Effectively Knocks Down Gene Expression but Causes Cellular Toxicity in Canines

PubMed Central

Sleeper, Meg M.; Reynolds, Caryn; Gazzara, Jeffrey; Withnall, Elanor; Singletary, Gretchen E.; Buchlis, George; Hui, Daniel; High, Katherine A.; Gao, Guangping; Wilson, James M.; Sweeney, H. Lee

2011-01-01

Abstract Derangements in calcium cycling have been described in failing hearts, and preclinical studies have suggested that therapies aimed at correcting this defect can lead to improvements in cardiac function and survival. One strategy to improve calcium cycling would be to inhibit phospholamban (PLB), the negative regulator of SERCA2a that is upregulated in failing hearts. The goal of this study was to evaluate the safety and efficacy of using adeno-associated virus (AAV)-mediated cardiac gene transfer of short hairpin RNA (shRNA) to knock down expression of PLB. Six dogs were treated with self-complementary AAV serotype 6 (scAAV6) expressing shRNA against PLB. Three control dogs were treated with empty AAV6 capsid, and two control dogs were treated with scAAV6 expressing dominant negative PLB. Vector was delivered via a percutaneously inserted cardiac injection catheter. PLB mRNA and protein expression were analyzed in three of six shRNA dogs between days 16 and 26. The other three shRNA dogs and five control dogs were monitored long-term to assess cardiac safety. PLB mRNA was reduced 16-fold, and PLB protein was reduced 5-fold, with treatment. Serum troponin elevation and depressed cardiac function were observed in the shRNA group only at 4 weeks. An enzyme-linked immunospot assay failed to detect any T cells reactive to AAV6 capsid in peripheral blood mononuclear cells, heart, or spleen. Microarray analysis revealed alterations in cardiac expression of several microRNAs with shRNA treatment. AAV6-mediated cardiac gene transfer of shRNA effectively knocks down PLB expression but is associated with severe cardiac toxicity. Toxicity may result from dysregulation of endogenous microRNA pathways. PMID:21542669

Serial changes in anatomy and ventricular function on dual-source cardiac computed tomography after the Norwood procedure for hypoplastic left heart syndrome.

PubMed

Goo, Hyun Woo

2017-12-01

Accurate evaluation of anatomy and ventricular function after the Norwood procedure in hypoplastic left heart syndrome is important for treatment planning and prognostication, but echocardiography and cardiac MRI have limitations. To assess serial changes in anatomy and ventricular function on dual-source cardiac CT after the Norwood procedure for hypoplastic left heart syndrome. In 14 consecutive patients with hypoplastic left heart syndrome, end-systolic and end-diastolic phase cardiac dual-source CT was performed before and early (average: 1 month) after the Norwood procedure, and repeated late (median: 4.5 months) after the Norwood procedure in six patients. Ventricular functional parameters and indexed morphological measurements including pulmonary artery size, right ventricular free wall thickness, and ascending aorta size on cardiac CT were compared between different time points. Moreover, morphological features including ventricular septal defect, endocardial fibroelastosis and coronary ventricular communication were evaluated on cardiac CT. Right ventricular function and volumes remained unchanged (indexed end-systolic and end-diastolic volumes: 38.9±14.0 vs. 41.1±21.5 ml/m 2 , P=0.7 and 99.5±30.5 vs. 105.1±33.0 ml/m 2 , P=0.6; ejection fraction: 60.1±7.3 vs. 63.8±7.0%, P=0.1, and indexed stroke volume: 60.7±18.0 vs. 64.0±15.6 ml/m 2 , P=0.5) early after the Norwood procedure, but function was decreased (ejection fraction: 64.2±2.6 vs. 58.1±7.1%, P=0.01) and volume was increased (indexed end-systolic and end-diastolic volumes: 39.2±14.9 vs. 68.9±20.6 ml/m 2 , P<0.003 and 107.8±36.5 vs. 162.9±36.2 ml/m 2 , P<0.006, and indexed stroke volume: 68.6±21.7 vs. 94.0±21.3 ml/m 2 , P=0.02) later. Branch pulmonary artery size showed a gradual decrease without asymmetry after the Norwood procedure. Right and left pulmonary artery stenoses were identified in 21.4% (3/14) of the patients. Indexed right ventricular free wall thickness showed a significant increase early after the Norwood procedure (25.5±3.5 vs. 34.8±5.1 mm/m 2 , P=0.01) and then a significant decrease late after the Norwood procedure (34.8±5.1 vs. 27.2±4.2 mm/m 2 , P<0.0001). The hypoplastic ascending aorta smaller than 2 mm in diameter was identified in 21.4% (3/14) of the patients. Ventricular septal defect (n=3), endocardial fibroelastosis (n=2) and coronary ventricular communication (n=1) were detected on cardiac CT. Cardiac CT can be used to assess serial changes in anatomy and ventricular function after the Norwood procedure in patients with hypoplastic left heart syndrome.

Impact of metoprolol treatment on cardiac function and exercise tolerance in heart failure patients with neuropsychiatric disorders.

PubMed

Huang, Jingjing; Zhang, Ran; Liu, Xuelu; Meng, Yong

2018-01-01

To investigate the impact of neuropsychiatric disorders on the effect of metoprolol on cardiac and motor function in chronic heart failure (CHF) patients. From February 2013 to April 2016, CHF patients with clinical mental disorders received metoprolol (23.75 or 47.5 mg, once daily, orally) at the Second Affiliated Hospital of Kunming Medical University. Mental status was confirmed by means of the Hospital Anxiety and Depression Scale (HADS) and the Copenhagen Burnout Inventory (CBI) scale. Cardiac function parameters such as systolic blood pressure (SBP), ejection fraction (EF) and cardiac index (CI) as well as motor function including the 6 meter walk test (6MWT) and the Veteran's Specific Activity Questionnaire (VSAQ) were assessed as primary outcomes of the study. A total of 154 patients (median age, 66.39 years; men, n = 101) were allocated into eight groups based on their mental status. There were no significant differences in heart rate (HR) or SBP control achieved by metoprolol in any groups compared with the control (patients with normal mental status). Furthermore, biphasic ejection fraction (EF) changes were observed in all the groups with a decrease in the first month and increase from the sixth month. However, this increase was significantly lower (p < .001) than the EF achieved with metoprolol treatment in the control group except for the anxiety group. A similar pattern was seen for CI, 6MWT and VSAQ changes in all the groups. Patients in the anxiety group responded similarly to the patients with normal mental status. Depressive and high burnout symptoms, but not anxiety, lower the improvement of cardiac and motor function by metoprolol treatment in CHF.

N-terminal pro–brain natriuretic peptide and abnormal brain aging

PubMed Central

Sabayan, Behnam; van Buchem, Mark A.; de Craen, Anton J.M.; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B.; Gudnason, Vilmundur; Arai, Andrew E.

2015-01-01

Objective: To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. Methods: In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. Results: In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p < 0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Conclusions: Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. PMID:26231259

Fermitins, the Orthologs of Mammalian Kindlins, Regulate the Development of a Functional Cardiac Syncytium in Drosophila melanogaster

PubMed Central

Catterson, James H.; Heck, Margarete M. S.; Hartley, Paul S.

2013-01-01

The vertebrate Kindlins are an evolutionarily conserved family of proteins critical for integrin signalling and cell adhesion. Kindlin-2 (KIND2) is associated with intercalated discs in mice, suggesting a role in cardiac syncytium development; however, deficiency of Kind2 leads to embryonic lethality. Morpholino knock-down of Kind2 in zebrafish has a pleiotropic effect on development that includes the heart. It therefore remains unclear whether cardiomyocyte Kind2 expression is required for cardiomyocyte junction formation and the development of normal cardiac function. To address this question, the expression of Fermitin 1 and Fermitin 2 (Fit1, Fit2), the two Drosophila orthologs of Kind2, was silenced in Drosophila cardiomyocytes. Heart development was assessed in adult flies by immunological methods and videomicroscopy. Silencing both Fit1 and Fit2 led to a severe cardiomyopathy characterised by the failure of cardiomyocytes to develop as a functional syncytium and loss of synchrony between cardiomyocytes. A null allele of Fit1 was generated but this had no impact on the heart. Similarly, the silencing of Fit2 failed to affect heart function. In contrast, the silencing of Fit2 in the cardiomyocytes of Fit1 null flies disrupted syncytium development, leading to severe cardiomyopathy. The data definitively demonstrate a role for Fermitins in the development of a functional cardiac syncytium in Drosophila. The findings also show that the Fermitins can functionally compensate for each other in order to control syncytium development. These findings support the concept that abnormalities in cardiomyocyte KIND2 expression or function may contribute to cardiomyopathies in humans. PMID:23690969

Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

PubMed

Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

2014-11-01

Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering.

PubMed

Navaei, Ali; Truong, Danh; Heffernan, John; Cutts, Josh; Brafman, David; Sirianni, Rachael W; Vernon, Brent; Nikkhah, Mehdi

2016-03-01

Injectable biomaterials offer a non-invasive approach to deliver cells into the myocardial infarct region to maintain a high level of cell retention and viability and initiate the regeneration process. However, previously developed injectable matrices often suffer from low bioactivity or poor mechanical properties. To address this need, we introduced a biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with excellent bioactivity as well as mechanical robustness for cardiac tissue engineering. A unique feature of our work was that we performed extensive in vitro biological analyses to assess the functionalities of cardiomyocytes (CMs) alone and in co-culture with cardiac fibroblasts (CFs) (2:1 ratio) within the hydrogel matrix. The synthesized hydrogel exhibited viscoelastic behavior (storage modulus: 1260 Pa) and necessary water content (75%) to properly accommodate the cardiac cells. The encapsulated cells demonstrated a high level of cell survival (90% for co-culture condition, day 7) and spreading throughout the hydrogel matrix in both culture conditions. A dense network of stained F-actin fibers (∼ 6 × 10(4) μm(2) area coverage, co-culture condition) illustrated the formation of an intact and three dimensional (3D) cell-embedded matrix. Furthermore, immunostaining and gene expression analyses revealed mature phenotypic characteristics of cardiac cells. Notably, the co-culture group exhibited superior structural organization and cell-cell coupling, as well as beating behavior (average ∼ 45 beats per min, co-culture condition, day 7). The outcome of this study is envisioned to open a new avenue for extensive in vitro characterization of injectable matrices embedded with 3D mono- and co-culture of cardiac cells prior to in vivo experiments. In this work, we synthesized a new class of biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with suitable bioactivity and mechanical properties for cardiac tissue engineering. A significant aspect of our work was that we performed extensive in vitro biological analyses to assess the functionality of cardiomyocytes alone and in co-culture with cardiac fibroblasts encapsulated within the 3D hydrogel matrix. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparison of simultaneous and sequential SPECT imaging for discrimination tasks in assessment of cardiac defects.

PubMed

Trott, C M; Ouyang, J; El Fakhri, G

2010-11-21

Simultaneous rest perfusion/fatty-acid metabolism studies have the potential to replace sequential rest/stress perfusion studies for the assessment of cardiac function. Simultaneous acquisition has the benefits of increased signal and lack of need for patient stress, but is complicated by cross-talk between the two radionuclide signals. We consider a simultaneous rest (99m)Tc-sestamibi/(123)I-BMIPP imaging protocol in place of the commonly used sequential rest/stress (99m)Tc-sestamibi protocol. The theoretical precision with which the severity of a cardiac defect and the transmural extent of infarct can be measured is computed for simultaneous and sequential SPECT imaging, and their performance is compared for discriminating (1) degrees of defect severity and (2) sub-endocardial from transmural defects. We consider cardiac infarcts for which reduced perfusion and metabolism are observed. From an information perspective, simultaneous imaging is found to yield comparable or improved performance compared with sequential imaging for discriminating both severity of defect and transmural extent of infarct, for three defects of differing location and size.

Transcatheter Pulmonary Valve Replacement by Hybrid Approach Using a Novel Polymeric Prosthetic Heart Valve: Proof of Concept in Sheep

PubMed Central

Xu, Tong-yi; Zhang, Zhi-gang; Li, Xin; Han, Lin; Xu, Zhi-yun

2014-01-01

Background Since 2000, transcatheter pulmonary valve replacement has steadily advanced. However, the available prosthetic valves are restricted to bioprosthesis which have defects like poor durability. Polymeric heart valve is thought as a promising alternative to bioprosthesis. In this study, we introduced a novel polymeric transcatheter pulmonary valve and evaluated its feasibility and safety in sheep by a hybrid approach. Methods We designed a novel polymeric trileaflet transcatheter pulmonary valve with a balloon-expandable stent, and the valve leaflets were made of 0.1-mm expanded polytetrafluoroethylene (ePTFE) coated with phosphorylcholine. We chose glutaraldehyde-treated bovine pericardium valves as control. Pulmonary valve stents were implanted in situ by a hybrid transapical approach in 10 healthy sheep (8 for polymeric valve and 2 for bovine pericardium valve), weighing an average of 22.5±2.0 kg. Angiography and cardiac catheter examination were performed after implantation to assess immediate valvular functionality. After 4-week follow-up, angiography, echocardiography, computed tomography, and cardiac catheter examination were used to assess early valvular function. One randomly selected sheep with polymeric valve was euthanized and the explanted valved stent was analyzed macroscopically and microscopically. Findings Implantation was successful in 9 sheep. Angiography at implantation showed all 9 prosthetic valves demonstrated orthotopic position and normal functionality. All 9 sheep survived at 4-week follow-up. Four-week follow-up revealed no evidence of valve stent dislocation or deformation and normal valvular and cardiac functionality. The cardiac catheter examination showed the peak-peak transvalvular pressure gradient of the polymeric valves was 11.9±5.0 mmHg, while that of two bovine pericardium valves were 11 and 17 mmHg. Gross morphology demonstrated good opening and closure characteristics. No thrombus or calcification was seen macroscopically. Conclusions This design of the novel ePTFE transcatheter pulmonary valve is safe and effective to deploy in sheep by hybrid approach, and the early valvular functionality is good. PMID:24926892

2D Echocardiographic Evaluation of Right Ventricular Function Correlates With 3D Volumetric Models in Cardiac Surgery Patients.

PubMed

Magunia, Harry; Schmid, Eckhard; Hilberath, Jan N; Häberle, Leo; Grasshoff, Christian; Schlensak, Christian; Rosenberger, Peter; Nowak-Machen, Martina

2017-04-01

The early diagnosis and treatment of right ventricular (RV) dysfunction are of critical importance in cardiac surgery patients and impact clinical outcome. Two-dimensional (2D) transesophageal echocardiography (TEE) can be used to evaluate RV function using surrogate parameters due to complex RV geometry. The aim of this study was to evaluate whether the commonly used visual evaluation of RV function and size using 2D TEE correlated with the calculated three-dimensional (3D) volumetric models of RV function. Retrospective study, single center, University Hospital. Seventy complete datasets were studied consisting of 2D 4-chamber view loops (2-3 beats) and the corresponding 4-chamber view 3D full-volume loop of the right ventricle. RV function and RV size of the 2D loops then were assessed retrospectively purely qualitatively individually by 4 clinician echocardiographers certified in perioperative TEE. Corresponding 3D volumetric models calculating RV ejection fraction and RV end-diastolic volumes then were established and compared with the 2D assessments. 2D assessment of RV function correlated with 3D volumetric calculations (Spearman's rho -0.5; p<0.0001). No correlation could be established between 2D estimates of RV size and actual 3D volumetric end-diastolic volumes (Spearman's rho 0.15; p = 0.25). The 2D assessment of right ventricular function based on visual estimation as frequently used in clinical practice appeared to be a reliable method of RV functional evaluation. However, 2D assessment of RV size seemed unreliable and should be used with caution. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between cardiac autonomic function and cognitive function in Alzheimer's disease.

PubMed

Nonogaki, Zen; Umegaki, Hiroyuki; Makino, Taeko; Suzuki, Yusuke; Kuzuya, Masafumi

2017-01-01

Alzheimer's disease (AD) affects many central nervous structures and neurotransmitter systems. These changes affect not only cognitive function, but also cardiac autonomic function. However, the functional relationship between cardiac autonomic function and cognition in AD has not yet been investigated. The objective of the present study was to evaluate the association between cardiac autonomic function measured by heart rate variability and cognitive function in AD. A total of 78 AD patients were recruited for this study. Cardiac autonomic function was evaluated using heart rate variability analysis. Multiple linear regression analysis was used to model the association between heart rate variability and cognitive function (global cognitive function, memory, executive function and processing speed), after adjustment for covariates. Global cognitive function was negatively associated with sympathetic modulation (low-to-high frequency power ratio). Memory performance was positively associated with parasympathetic modulation (high frequency power) and negatively associated with sympathetic modulation (low-to-high frequency power ratio). These associations were independent of age, sex, educational years, diabetes, hypertension and cholinesterase inhibitor use. Cognitive function, especially in the areas of memory, is associated with cardiac autonomic function in AD. Specifically, lower cognitive performance was found to be associated with significantly higher cardiac sympathetic and lower parasympathetic function in AD. Geriatr Gerontol Int 2017; 17: 92-98. © 2015 Japan Geriatrics Society.

Simultaneous pressure-volume measurements using optical sensors and MRI for left ventricle function assessment during animal experiment.

PubMed

Abi-Abdallah Rodriguez, Dima; Durand, Emmanuel; de Rochefort, Ludovic; Boudjemline, Younes; Mousseaux, Elie

2015-01-01

Simultaneous pressure and volume measurements enable the extraction of valuable parameters for left ventricle function assessment. Cardiac MR has proven to be the most accurate method for volume estimation. Nonetheless, measuring pressure simultaneously during MRI acquisitions remains a challenge given the magnetic nature of the widely used pressure transducers. In this study we show the feasibility of simultaneous in vivo pressure-volume acquisitions with MRI using optical pressure sensors. Pressure-volume loops were calculated while inducing three inotropic states in a sheep and functional indices were extracted, using single beat loops, to characterize systolic and diastolic performance. Functional indices evolved as expected in response to positive inotropic stimuli. The end-systolic elastance, representing the contractility index, the diastolic myocardium compliance, and the cardiac work efficiency all increased when inducing inotropic state enhancement. The association of MRI and optical pressure sensors within the left ventricle successfully enabled pressure-volume loop analysis after having respective data simultaneously recorded during the experimentation without the need to move the animal between each inotropic state. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.

PubMed

Feng, Qiaoli; Lu, Chengzhi; Wang, Li; Song, Lijun; Li, Chao; Uppada, Ravi Chandra

2017-02-17

This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action. Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47 phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively. We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47 phox ,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0.092 and 0.931, respectively). Importantly, the expression of TH, AngII and Ang(1-7) was positively correlated with MDA and negatively correlated with SOD. Between-group comparisons demonstrated no differences in serum creatinine (P = 0.706). RDN attenuated cardiac remodelling and improved heart function by decreasing the level of cardiac oxidative stress and the local activity of the SNS and RAS in cardiac tissues. Additionally, the safety of the RDN procedure was established, as no significant decrease in LVSP or rise in serum creatinine was observed in our study.

Lentiviral Vectors Bearing the Cardiac Promoter of the Na+-Ca2+ Exchanger Report Cardiogenic Differentiation in Stem Cells

PubMed Central

Barth, Andreas S; Kizana, Eddy; Smith, Rachel R; Terrovitis, John; Dong, Peihong; Leppo, Michelle K; Zhang, Yiqiang; Miake, Junichiro; Olson, Eric N; Schneider, Jay W; Abraham, M Roselle; Marbán, Eduardo

2009-01-01

Cardiosphere-derived resident cardiac stem cells (CDCs) are readily isolated from adult hearts and confer functional benefit in animal models of heart failure. To study cardiogenic differentiation in CDCs, we developed a method to genetically label and selectively enrich for cells that have acquired a cardiac phenotype. Lentiviral vectors achieved significantly higher transduction efficiencies in CDCs than any of the nine adeno-associated viral (AAV) serotypes tested. To define the most suitable vector system for reporting cardiogenic differentiation, we compared the cell specificity of five commonly-used cardiac-specific promoters in the context of lentiviral vectors. The promoter of the cardiac sodium-calcium exchanger (NCX1) conveyed the highest degree of cardiac specificity, as assessed by transducing seven cell types with each vector and measuring fluorescence intensity by flow cytometry. NCX1-GFP-positive CDC subpopulations, demonstrating prolonged expression of a variety of cardiac markers, could be isolated and expanded in vitro. Finally, we used chemical biology to validate that lentiviral vectors bearing the cardiac NCX1-promoter can serve as a highly accurate biosensor of cardiogenic small molecules in stem cells. The ability to accurately report cardiac fate and selectively enrich for cardiomyocytes and their precursors has important implications for drug discovery and the development of cell-based therapies. PMID:18388932

Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation

PubMed Central

Li, Wenju; Li, Xiaoli; Zheng, Qiangsun; Niu, Xiaolin

2017-01-01

Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson’s trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR59230A. Our study suggested that aerobic exercise training could improve cardiac systolic function and alleviate LV chamber dilation, cardiac fibrosis and hypertrophy in HF mice. The mechanism responsible for the protective effects of aerobic exercise is associated with the activation of the β3-AR-nNOS-NO pathway. PMID:28622359

Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation.

PubMed

Wang, Bin; Xu, Ming; Li, Wenju; Li, Xiaoli; Zheng, Qiangsun; Niu, Xiaolin

2017-01-01

Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson's trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR59230A. Our study suggested that aerobic exercise training could improve cardiac systolic function and alleviate LV chamber dilation, cardiac fibrosis and hypertrophy in HF mice. The mechanism responsible for the protective effects of aerobic exercise is associated with the activation of the β3-AR-nNOS-NO pathway.

Cardiovascular research in space - Considerations for the design of the human research facility of the United States Space Station

NASA Technical Reports Server (NTRS)

Charles, J. B.; Bungo, M. W.

1986-01-01

The design of the Space Station's Human Research Facility for the collection of information on the long-time physiological adjustments of humans to space is described. The Space Life Sciences-1 mission will carry a rack-mounted echocardiograph for cardiac imaging, a mass spectrometer for cardiac output and respiratory function assessments at rest and during exercise, and a device to stimulate the carotid sinus baroreceptors and measure the resulting changes in heart rate.

Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin.

PubMed

Okere, Isidore C; Chandler, Margaret P; McElfresh, Tracy A; Rennison, Julie H; Sharov, Victor; Sabbah, Hani N; Tserng, Kou-Yi; Hoit, Brian D; Ernsberger, Paul; Young, Martin E; Stanley, William C

2006-07-01

Fatty acids are the primary fuel for the heart and are ligands for peroxisome proliferator-activated receptors (PPARs), which regulate the expression of genes encoding proteins involved in fatty acid metabolism. Saturated fatty acids, particularly palmitate, can be converted to the proapoptotic lipid intermediate ceramide. This study assessed cardiac function, expression of PPAR-regulated genes, and cardiomyocyte apoptosis in rats after 8 wk on either a low-fat diet [normal chow control (NC); 10% fat calories] or high-fat diets composed mainly of either saturated (Sat) or unsaturated fatty acids (Unsat) (60% fat calories) (n = 10/group). The Sat group had lower plasma insulin and leptin concentrations compared with the NC or Unsat groups. Cardiac function and mass and body mass were not different. Cardiac triglyceride content was increased in the Sat and Unsat groups compared with NC (P < 0.05); however, ceramide content was higher in the Sat group compared with the Unsat group (2.9 +/- 0.2 vs. 1.4 +/- 0.2 nmol/g; P < 0.05), whereas the NC group was intermediate (2.3 +/- 0.3 nmol/g). The number of apoptotic myocytes, assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining, was higher in the Sat group compared with the Unsat group (0.28 +/- 0.05 vs. 0.17 +/- 0.04 apoptotic cells/1,000 nuclei; P < 0.04) and was positively correlated to ceramide content (P < 0.02). Both high-fat diets increased the myocardial mRNA expression of the PPAR-regulated genes encoding uncoupling protein-3 and pyruvate dehydrogenase kinase-4, but only the Sat diet upregulated medium-chain acyl-CoA dehydrogenase. In conclusion, dietary fatty acid composition affects cardiac ceramide accumulation, cardiomyocyte apoptosis, and expression of PPAR-regulated genes independent of cardiac mass or function.

Dynamic and quantitative evaluation of degenerative mitral valve disease: a dedicated framework based on cardiac magnetic resonance imaging

PubMed Central

Onorati, Francesco; Puppini, Giovanni; Pappalardo, Omar A.; Selmi, Matteo; Votta, Emiliano; Faggian, Giuseppe; Redaelli, Alberto

2017-01-01

Background Accurate quantification of mitral valve (MV) morphology and dynamic behavior over the cardiac cycle is crucial to understand the mechanisms of degenerative MV dysfunction and to guide the surgical intervention. Cardiac magnetic resonance (CMR) imaging has progressively been adopted to evaluate MV pathophysiology, although a dedicated framework is required to perform a quantitative assessment of the functional MV anatomy. Methods We investigated MV dynamic behavior in subjects with normal MV anatomy (n=10) and patients referred to surgery due to degenerative MV prolapse, classified as fibro-elastic deficiency (FED, n=9) and Barlow’s disease (BD, n=10). A CMR-dedicated framework was adopted to evaluate prolapse height and volume and quantitatively assess valvular morphology and papillary muscles (PAPs) function over the cardiac cycle. Multiple comparison was used to investigate the hallmarks associated to MV degenerative prolapse and evaluate the feasibility of anatomical and functional distinction between FED and BD phenotypes. Results On average, annular dimensions were significantly (P<0.05) larger in BD than in FED and normal subjects while no significant differences were noticed between FED and normal. MV eccentricity progressively decreased passing from normal to FED and BD, with the latter exhibiting a rounder annulus shape. Over the cardiac cycle, we noticed significant differences for BD during systole with an abnormal annular enlargement between mid and late systole (LS) (P<0.001 vs. normal); the PAPs dynamics remained comparable in the three groups. Prolapse height and volume highlighted significant differences among normal, FED and BD valves. Conclusions Our CMR-dedicated framework allows for the quantitative and dynamic evaluation of MV apparatus, with quantifiable annular alterations representing the primary hallmark of severe MV degeneration. This may aid surgeons in the evaluation of the severity of MV dysfunction and the selection of the appropriate MV treatment. PMID:28540065

Assessing Cardiac Injury in Mice With Dual Energy-MicroCT, 4D-MicroCT, and MicroSPECT Imaging After Partial Heart Irradiation

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

Lee, Chang-Lung; Min, Hooney; Befera, Nicholas

Purpose: To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging using micro-single photon emission computed tomography (SPECT). Methods and Materials: To study cardiac injury from tangent field irradiation in mice, we used a small-field biological irradiator to deliver a single dose of 12 Gy x-rays to approximately one-third of the left ventricle (LV) of Tie2Cre; p53{sup FL/+} and Tie2Cre; p53{sup FL/−} mice, where 1 or both alleles of p53 are deleted in endothelialmore » cells. Four and 8 weeks after irradiation, mice were injected with gold and iodinated nanoparticle-based contrast agents, and imaged with DE-microCT and 4D-microCT to evaluate myocardial vascular permeability and cardiac function, respectively. Additionally, the same mice were imaged with microSPECT to assess myocardial perfusion. Results: After PHI with tangent fields, DE-microCT scans showed a time-dependent increase in accumulation of gold nanoparticles (AuNp) in the myocardium of Tie2Cre; p53{sup FL/−} mice. In Tie2Cre; p53{sup FL/−} mice, extravasation of AuNp was observed within the irradiated LV, whereas in the myocardium of Tie2Cre; p53{sup FL/+} mice, AuNp were restricted to blood vessels. In addition, data from DE-microCT and microSPECT showed a linear correlation (R{sup 2} = 0.97) between the fraction of the LV that accumulated AuNp and the fraction of LV with a perfusion defect. Furthermore, 4D-microCT scans demonstrated that PHI caused a markedly decreased ejection fraction, and higher end-diastolic and end-systolic volumes, to develop in Tie2Cre; p53{sup FL/−} mice, which were associated with compensatory cardiac hypertrophy of the heart that was not irradiated. Conclusions: Our results show that DE-microCT and 4D-microCT with nanoparticle-based contrast agents are novel imaging approaches complementary to microSPECT for noninvasive assessment of the change in myocardial vascular permeability and cardiac function of mice in whom myocardial injury develops after PHI.« less

Cardiovascular adaptation to extrauterine life after intrauterine growth restriction.

PubMed

Rodriguez-Guerineau, Luciana; Perez-Cruz, Miriam; Gomez Roig, María D; Cambra, Francisco J; Carretero, Juan; Prada, Fredy; Gómez, Olga; Crispi, Fátima; Bartrons, Joaquim

2018-02-01

Introduction The adaptive changes of the foetal heart in intrauterine growth restriction can persist postnatally. Data regarding its consequences for early circulatory adaptation to extrauterine life are scarce. The aim of this study was to assess cardiac morphometry and function in newborns with late-onset intrauterine growth restriction to test the hypothesis that intrauterine growth restriction causes cardiac shape and functional changes at birth. A comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates. Compared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e') diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group. Neonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.

No overt structural or functional changes associated with PEG-coated gold nanoparticles accumulation with acute exposure in the mouse heart.

PubMed

Yang, Chengzhi; Yang, Hui; Wu, Jimin; Meng, Zenghui; Xing, Rui; Tian, Aiju; Tian, Xin; Guo, Lijun; Zhang, Youyi; Nie, Guangjun; Li, Zijian

2013-10-24

In this study, we investigated the cardiac biodistribution of polyethylene glycol (PEG)-coated AuNPs and their effects on cardiac function, structure and inflammation in both normal and cardiac remodeling mice. The model of cardiac remodeling was induced by subcutaneously injection of isoproterenol (ISO), a non-selective beta-adrenergic agonist, for 7 days. After AuNPs were injected intravenously in mice for 7 consecutive days, Au content in different organs was determined quantitatively by inductively coupled plasma mass spectrometry (ICP-MS), cardiac function and structure were measured by echocardiography, cardiac fibrosis was examined with picrosirius red staining, the morphology of cardiomyocytes was observed with hematoxylin and eosin (H & E) staining. The accumulation of AuNPs in hearts did not affect cardiac function or induce cardiac hypertrophy, cardiac fibrosis and cardiac inflammation under normal physiological condition. Cardiac AuNPs content was 6-fold higher in the cardiac remodeling mouse than normal mice. However, the increased accumulation of AuNPs in the heart did not aggravate ISO-induced cardiac hypertrophy, cardiac fibrosis or cardiac inflammation. These observations suggest that PEG-coated AuNPs possess excellent biocompatibility under both physiological and pathological conditions. Thus, AuNPs may be safe for cardiac patients and hold great promise for further development for various biomedical applications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Preserved heart function and maintained response to cardiac stresses in a genetic model of cardiomyocyte-targeted deficiency of cyclooxygenase-2

PubMed Central

Papanicolaou, Kyriakos N.; Streicher, John M.; Ishikawa, Tomo-o; Herschman, Harvey; Wang, Yibin; Walsh, Kenneth

2010-01-01

Cyclooxygenase-1 and -2 are rate-limiting enzymes in the formation of a wide array of bioactive lipid mediators collectively known as prostanoids (prostaglandins, prostacyclins, thromboxanes). Evidence from clinical trials shows that selective inhibition of the second isoenzyme (cyclooxygenase-2, or Cox-2) is associated with increased risk for serious cardiovascular events and findings from animal-based studies have suggested protective roles of Cox-2 for the heart. To further characterize the function of Cox-2 in the heart, mice with loxP sites flanking exons 4 and 5 of Cox-2 were rendered knockout specifically in cardiac myocytes (Cox-2 CKO mice) via cre-mediated recombination. Baseline cardiac performance of CKO mice remained unchanged and closely resembled that of control mice. Furthermore, myocardial infarct size induced after in vivo ischemia/reperfusion (I/R) injury was comparable between CKO and control mice. In addition, cardiac hypertrophy and function four weeks after transverse aortic constriction (TAC) was found to be similar between the two groups. Assessment of Cox-2 expression in purified adult cardiac cells isolated after I/R and TAC suggests that the dominant source of Cox-2 is found in the non-myocyte fraction. In conclusion, our animal-based analyses together with the cell-based observations portray a limited role of cardiomyocyte-produced Cox-2 at baseline and in the context of ischemic or hemodynamic challenge. PMID:20399788

52 Genetic Loci Influencing Myocardial Mass

PubMed Central

van der Harst, Pim; van Setten, Jessica; Verweij, Niek; Vogler, Georg; Franke, Lude; Maurano, Matthew T.; Wang, Xinchen; Leach, Irene Mateo; Eijgelsheim, Mark; Sotoodehnia, Nona; Hayward, Caroline; Sorice, Rossella; Meirelles, Osorio; Lyytikäinen, Leo-Pekka; Polašek, Ozren; Tanaka, Toshiko; Arking, Dan E.; Ulivi, Sheila; Trompet, Stella; Müller-Nurasyid, Martina; Smith, Albert V.; Dörr, Marcus; Kerr, Kathleen F.; Magnani, Jared W.; Fabiola Del Greco, M.; Zhang, Weihua; Nolte, Ilja M.; Silva, Claudia T.; Padmanabhan, Sandosh; Tragante, Vinicius; Esko, Tõnu; Abecasis, Gonçalo R.; Adriaens, Michiel E.; Andersen, Karl; Barnett, Phil; Bis, Joshua C.; Bodmer, Rolf; Buckley, Brendan M.; Campbell, Harry; Cannon, Megan V.; Chakravarti, Aravinda; Chen, Lin Y.; Delitala, Alessandro; Devereux, Richard B.; Doevendans, Pieter A.; Dominiczak, Anna F.; Ferrucci, Luigi; Ford, Ian; Gieger, Christian; Harris, Tamara B.; Haugen, Eric; Heinig, Matthias; Hernandez, Dena G.; Hillege, Hans L.; Hirschhorn, Joel N.; Hofman, Albert; Hubner, Norbert; Hwang, Shih-Jen; Iorio, Annamaria; Kähönen, Mika; Kellis, Manolis; Kolcic, Ivana; Kooner, Ishminder K.; Kooner, Jaspal S.; Kors, Jan A.; Lakatta, Edward G.; Lage, Kasper; Launer, Lenore J.; Levy, Daniel; Lundby, Alicia; Macfarlane, Peter W.; May, Dalit; Meitinger, Thomas; Metspalu, Andres; Nappo, Stefania; Naitza, Silvia; Neph, Shane; Nord, Alex S.; Nutile, Teresa; Okin, Peter M.; Olsen, Jesper V.; Oostra, Ben A.; Penninger, Josef M.; Pennacchio, Len A.; Pers, Tune H.; Perz, Siegfried; Peters, Annette; Pinto, Yigal M.; Pfeufer, Arne; Pilia, Maria Grazia; Pramstaller, Peter P.; Prins, Bram P.; Raitakari, Olli T.; Raychaudhuri, Soumya; Rice, Ken M.; Rossin, Elizabeth J.; Rotter, Jerome I.; Schafer, Sebastian; Schlessinger, David; Schmidt, Carsten O.; Sehmi, Jobanpreet; Silljé, Herman H.W.; Sinagra, Gianfranco; Sinner, Moritz F.; Slowikowski, Kamil; Soliman, Elsayed Z.; Spector, Timothy D.; Spiering, Wilko; Stamatoyannopoulos, John A.; Stolk, Ronald P.; Strauch, Konstantin; Tan, Sian-Tsung; Tarasov, Kirill V.; Trinh, Bosco; Uitterlinden, Andre G.; van den Boogaard, Malou; van Duijn, Cornelia M.; van Gilst, Wiek H.; Viikari, Jorma S.; Visscher, Peter M.; Vitart, Veronique; Völker, Uwe; Waldenberger, Melanie; Weichenberger, Christian X.; Westra, Harm-Jan; Wijmenga, Cisca; Wolffenbuttel, Bruce H.; Yang, Jian; Bezzina, Connie R.; Munroe, Patricia B.; Snieder, Harold; Wright, Alan F.; Rudan, Igor; Boyer, Laurie A.; Asselbergs, Folkert W.; van Veldhuisen, Dirk J.; Stricker, Bruno H.; Psaty, Bruce M.; Ciullo, Marina; Sanna, Serena; Lehtimäki, Terho; Wilson, James F.; Bandinelli, Stefania; Alonso, Alvaro; Gasparini, Paolo; Jukema, J. Wouter; Kääb, Stefan; Gudnason, Vilmundur; Felix, Stephan B.; Heckbert, Susan R.; de Boer, Rudolf A.; Newton-Cheh, Christopher; Hicks, Andrew A.; Chambers, John C.; Jamshidi, Yalda; Visel, Axel; Christoffels, Vincent M.; Isaacs, Aaron; Samani, Nilesh J.; de Bakker, Paul I.W.

2017-01-01

BACKGROUND Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10−8. These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets. PMID:27659466

Effects of local irradiation combined with sunitinib on early remodeling, mitochondria, and oxidative stress in the rat heart

PubMed Central

Sridharan, Vijayalakshmi; Thomas, Chanice J.; Cao, Maohua; Melnyk, Stepan B.; Pavliv, Oleksandra; Joseph, Jacob; Singh, Sharda P.; Sharma, Sunil; Moros, Eduardo G.; Boerma, Marjan

2016-01-01

Background and Purpose Thoracic (chemo)radiation therapy is increasingly administered with tyrosine kinase inhibitors (TKI). While TKI have adverse effects on the heart, it is unknown whether combination with other cancer therapies causes enhanced toxicity. We used an animal model to investigate whether radiation and sunitinib interact in their effects on the heart. Material and Methods Male Sprague-Dawley rats received local heart irradiation (9 Gy per day, 5 days). Oral sunitinib (8 or 15 mg/kg bodyweight per day) started on day 1 of irradiation and continued for 2 weeks. Cardiac function was examined with echocardiography. Cardiac remodeling, cell death, left ventricular (LV) oxidative stress markers, mitochondrial morphology and membrane permeability transition pore (mPTP) opening were assessed. Results Cardiac diameter, stroke volume, and LV volume, mass and anterior wall thickness increased in time, but only in the vehicle group. Sunitinib reduced LV inner diameter and volume in systole, which were counteracted by radiation. Sunitinib and radiation showed enhanced effects on mitochondrial morphology and mPTP opening, but not on cardiac troponin I, mast cell numbers or markers of oxidative stress. Conclusions This study found no early enhanced effects of radiation and sunitinib on cardiac function or structure. Long-term effects remain to be determined. PMID:27072940

Disruption of intracardiac flow patterns in the newborn infant.

PubMed

Groves, Alan M; Durighel, Giuliana; Finnemore, Anna; Tusor, Nora; Merchant, Nazakat; Razavi, Reza; Hajnal, Jo V; Edwards, A David

2012-04-01

Consistent patterns of rotational intracardiac flow have been demonstrated in the healthy adult human heart. Intracardiac rotational flow patterns are hypothesized to assist in the maintenance of kinetic energy of inflowing blood, augmenting cardiac function. Newborn cardiac function is known to be suboptimal secondary to decreased receptor number and sympathetic innervation, increased afterload, and increased reliance on atrial contraction to support ventricular filling. Patterns of intracardiac flow in the newborn have not previously been examined. Whereas 5 of the 13 infants studied showed significant evidence of rotational flow within the right atrium, 8 infants showed little or no rotational flow. Presence or absence of rotational flow was not related to gestational age, birth weight, postnatal age, atrial size, or image quality. Despite absence of intra-atrial rotational flow, atrioventricular valve flow into the left and right ventricles later in the cardiac cycle could be seen, suggesting that visualization techniques were adequate. While further study is required to assess its exact consequences on cardiac mechanics and energetics, disruption to intracardiac flow patterns could be another contributor to the multifactorial sequence that produces newborn circulatory failure. We studied 13 newborn infants, using three-dimensional (3D) cardiac magnetic resonance phase-contrast imaging (spatial resolution 0.84 mm, temporal resolution 22.6 ms) performed without sedation/anesthesia.

Cardio-oncology: the Nuclear Option.

PubMed

Alvarez, Jorge A; Russell, Raymond R

2017-04-01

Cardio-oncology focuses increased effort to decrease cancer treatment-related cardiotoxicity while continuing to improve outcomes. We sought to synthesize the latest in nuclear cardiology as it pertains to the assessment of left ventricular function in preventative guidelines and comparison to other modalities, novel molecular markers of pre-clinical cardiotoxicity, and its role in cardiac amyloid diagnosis. Planar ERNA (equilibrium radionuclide angiocardiography) provides a reliable and proven means of monitoring and preventing anthracycline cardiotoxicity, and SPECT ERNA using solid-state gamma cameras may provide reproducible assessments of left ventricular function with reduced radiation exposure. While certain chemotherapeutics have vascular side effects, the use of stress perfusion imaging has still not been adequately studied for routine use. Similarly, markers of apoptosis, inflammation, and sympathetic nerve dysfunction are promising, but are still not ready for uniform usage. SPECT tracers can assist in nonbiopsy diagnosis of cardiac amyloid. Nuclear cardiology is a significant contributor to the multimodality approach to cardio-oncology.

Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output.

PubMed

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1998-01-01

To determine whether prolonged (chronic) resuscitation has any beneficial effects on cardiac output and hepatocellular function after trauma-hemorrhage and acute fluid replacement. Acute fluid resuscitation after trauma-hemorrhage restores but does not maintain the depressed hepatocellular function and cardiac output. Male Sprague-Dawley rats underwent a 5-cm laparotomy (i.e., trauma was induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer's lactate (RL). The animals were acutely resuscitated with RL using 4 times the volume of maximum bleed-out over 60 minutes, followed by chronic resuscitation of 0, 5, or 10 mL/kg/hr RL for 20 hours. Hepatocellular function was determined by an in vivo indocyanine green clearance technique. Hepatic microvascular blood flow was assessed by laser Doppler flowmetry. Plasma levels of interleukin-6 (IL-6) were determined by bioassay. Chronic resuscitation with 5 mL/kg/hr RL, but not with 0 or 10 mL/kg/hr RL, restored cardiac output, hepatocellular function, and hepatic microvascular blood flow at 20 hours after hemorrhage. The regimen above also reduced plasma IL-6 levels. Because chronic resuscitation with 5 mL/kg/hr RL after trauma-hemorrhage and acute fluid replacement restored hepatocellular function and hepatic microvascular blood flow and decreased plasma levels of IL-6, we propose that chronic fluid resuscitation in addition to acute fluid replacement should be routinely used in experimental studies of trauma-hemorrhage.

Exercise-Induced Changes in Glucose Metabolism Promote Physiological Cardiac Growth

PubMed Central

Gibb, Andrew A.; Epstein, Paul N.; Uchida, Shizuka; Zheng, Yuting; McNally, Lindsey A.; Obal, Detlef; Katragadda, Kartik; Trainor, Patrick; Conklin, Daniel J.; Brittian, Kenneth R.; Tseng, Michael T.; Wang, Jianxun; Jones, Steven P.; Bhatnagar, Aruni

2017-01-01

Background: Exercise promotes metabolic remodeling in the heart, which is associated with physiological cardiac growth; however, it is not known whether or how physical activity–induced changes in cardiac metabolism cause myocardial remodeling. In this study, we tested whether exercise-mediated changes in cardiomyocyte glucose metabolism are important for physiological cardiac growth. Methods: We used radiometric, immunologic, metabolomic, and biochemical assays to measure changes in myocardial glucose metabolism in mice subjected to acute and chronic treadmill exercise. To assess the relevance of changes in glycolytic activity, we determined how cardiac-specific expression of mutant forms of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase affect cardiac structure, function, metabolism, and gene programs relevant to cardiac remodeling. Metabolomic and transcriptomic screenings were used to identify metabolic pathways and gene sets regulated by glycolytic activity in the heart. Results: Exercise acutely decreased glucose utilization via glycolysis by modulating circulating substrates and reducing phosphofructokinase activity; however, in the recovered state following exercise adaptation, there was an increase in myocardial phosphofructokinase activity and glycolysis. In mice, cardiac-specific expression of a kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase transgene (GlycoLo mice) lowered glycolytic rate and regulated the expression of genes known to promote cardiac growth. Hearts of GlycoLo mice had larger myocytes, enhanced cardiac function, and higher capillary-to-myocyte ratios. Expression of phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in the heart (GlycoHi mice) increased glucose utilization and promoted a more pathological form of hypertrophy devoid of transcriptional activation of the physiological cardiac growth program. Modulation of phosphofructokinase activity was sufficient to regulate the glucose–fatty acid cycle in the heart; however, metabolic inflexibility caused by invariantly low or high phosphofructokinase activity caused modest mitochondrial damage. Transcriptomic analyses showed that glycolysis regulates the expression of key genes involved in cardiac metabolism and remodeling. Conclusions: Exercise-induced decreases in glycolytic activity stimulate physiological cardiac remodeling, and metabolic flexibility is important for maintaining mitochondrial health in the heart. PMID:28860122

Challenges in Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Godier, Amandine; Maidhof, Robert; Marsano, Anna; Martens, Timothy P.; Radisic, Milica

2010-01-01

Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Engineered constructs can also serve as high-fidelity models for studies of cardiac development and disease. In a general case, the biological potential of the cell—the actual “tissue engineer”—is mobilized by providing highly controllable three-dimensional environments that can mediate cell differentiation and functional assembly. For cardiac regeneration, some of the key requirements that need to be met are the selection of a human cell source, establishment of cardiac tissue matrix, electromechanical cell coupling, robust and stable contractile function, and functional vascularization. We review here the potential and challenges of cardiac tissue engineering for developing therapies that could prevent or reverse heart failure. PMID:19698068

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

PubMed Central

2010-01-01

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

Transient Receptor Potential Vanilloid 2 Regulates Myocardial Response to Exercise

PubMed Central

Naticchioni, Mindi; Karani, Rajiv; Smith, Margaret A.; Onusko, Evan; Robbins, Nathan; Jiang, Min; Radzyukevich, Tatiana; Fulford, Logan; Gao, Xu; Apel, Ryan; Heiny, Judith; Rubinstein, Jack; Koch, Sheryl E.

2015-01-01

The myocardial response to exercise is an adaptive mechanism that permits the heart to maintain cardiac output via improved cardiac function and development of hypertrophy. There are many overlapping mechanisms via which this occurs with calcium handling being a crucial component of this process. Our laboratory has previously found that the stretch sensitive TRPV2 channels are active regulators of calcium handling and cardiac function under baseline conditions based on our observations that TRPV2-KO mice have impaired cardiac function at baseline. The focus of this study was to determine the cardiac function of TRPV2-KO mice under exercise conditions. We measured skeletal muscle at baseline in WT and TRPV2-KO mice and subjected them to various exercise protocols and measured the cardiac response using echocardiography and molecular markers. Our results demonstrate that the TRPV2-KO mouse did not tolerate forced exercise although they became increasingly exercise tolerant with voluntary exercise. This occurs as the cardiac function deteriorates further with exercise. Thus, our conclusion is that TRPV2-KO mice have impaired cardiac functional response to exercise. PMID:26356305

[Cardiac surgery in octogenarian patients: evaluation of predictive factors of mortality, long-term outcome and quality of life].

PubMed

Viana-Tejedor, Ana; Domínguez, Francisco J; Moreno Yangüela, Mar; Moreno, Raúl; López de Sá, Esteban; Mesa, José M; López-Sendón, José

2008-10-04

Increasing life expectancy in Western countries in the last decades has resulted in a significant gradual increasing number of octogenarians referred for cardiac surgery. There is a need for a critical evaluation of the long-term surgical outcome and quality of life in the elderly. The aim of this study is to identify risk factors of mortality in octogenarians undergoing cardiac surgery and to assess the long term survival and quality of life. Data were reviewed on 150 patients aged over 80 years--mean age (standard deviation): 82.7 (2.5) years--who underwent cardiac surgery at our institution in the last 26 years. We analyzed clinical and epidemiological variables included in the European System for Cardiac Operative Risk Evaluation (euroSCORE), in-hospital morbidity and mortality, long term survival and quality of life after cardiac surgery. The 30-day mortality rate was 30.1%, with a mean hospital stay of 16.5 days (13-27). Emergent procedure, reparation of postinfarction ventricular ruptures, New York Heart Association functional class IV, chronic renal failure and previous myocardial infarction were independent predictors of in-hospital mortality. Mean follow up was 72.2 (9.9) months with survival rates of 87.3% and 57% at 1 and 5 years, respectively. Late postoperative quality of life in our 53 long-term survivors was significantly better than prior to surgery. New York Heart Association functional class improved from 2.52 to 1.48. Most survivors (97.7%) were satisfied with present quality of life Cardiac surgery in octogenarians is associated with increased in-hospital mortality rate and longer hospital stay. Our findings support that cardiac surgery can be performed in a selected elderly population with good long-term survival and quality of life.

Effect of L-Carnitine Supplementation on Apelin and Apelin Receptor (Apj) Expression in Cardiac Muscle of Obese Diabetic Rats.

PubMed

Ranjbar Kohan, Neda; Nazifi, Saeed; Tabandeh, Mohammad Reza; Ansari Lari, Maryam

2018-10-01

L-carnitine (LC) has been shown to protect cardiac metabolism in diabetes patients with cardiovascular diseases (CVDs). Apelin, a newly discovered adipocytokines, is an important regulator of cardiac muscle function; however, the role of the level of expression of Apelin axis in improvement of cardiac function by LC in diabetic patients, is not clear. In the present study, obese insulin-resistant rats were used to determine the effect of LC, when given orally with a high-calorie diet, on Apelin and Apelin receptor (Apj) expression in cardiac muscle. In this experimental study, rats were fed with high-fat/high-carbohydrate diet for five weeks and subsequently were injected with streptozotocin 30 mg/kg for induction of obesity and insulin resistance. After confirming the induction of diabetes (serum glucose above 7.5 mmol/L), the animals received LC 300 mg/kg in drinking water for 28 days. On days 0, 14 and 28 after treatment, cardiac Apelin and Apj gene expression was evaluated by real time polymerase chain reaction (PCR) analysis. Serum levels of insulin, Apelin, glucose, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and the homeostasis model assessment of insulin resistance (HOMA-IR) were also measured using commercial kits. Cardiac Apelin and Apj expression and serum Apelin were increased in obese rats, while LC supplementation decreased the serum levels of Apelin and down-regulated Apelin and Apj expression in cardiac muscle. These changes were associated with reduced insulin resistance markers and serum inflammatory factors and improved lipid profile. We concluded that LC supplementation could attenuate the over-expression of Apelin axis in heart of diabetic rats, a novel mechanism by which LC improves cardiovascular complications in diabetic patients. Copyright© by Royan Institute. All rights reserved.

Cardiac-Specific Deletion of Pyruvate Dehydrogenase Impairs Glucose Oxidation Rates and Induces Diastolic Dysfunction.

PubMed

Gopal, Keshav; Almutairi, Malak; Al Batran, Rami; Eaton, Farah; Gandhi, Manoj; Ussher, John Reyes

2018-01-01

Obesity and type 2 diabetes (T2D) increase the risk for cardiomyopathy, which is the presence of ventricular dysfunction in the absence of underlying coronary artery disease and/or hypertension. As myocardial energy metabolism is altered during obesity/T2D (increased fatty acid oxidation and decreased glucose oxidation), we hypothesized that restricting myocardial glucose oxidation in lean mice devoid of the perturbed metabolic milieu observed in obesity/T2D would produce a cardiomyopathy phenotype, characterized via diastolic dysfunction. We tested our hypothesis via producing mice with a cardiac-specific gene knockout for pyruvate dehydrogenase (PDH, gene name Pdha1 ), the rate-limiting enzyme for glucose oxidation. Cardiac-specific Pdha1 deficient ( Pdha1 Cardiac-/- ) mice were generated via crossing a tamoxifen-inducible Cre expressing mouse under the control of the alpha-myosin heavy chain (αMHC-MerCreMer) promoter with a floxed Pdha1 mouse. Energy metabolism and cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Tamoxifen administration produced an ~85% reduction in PDH protein expression in Pdha1 Cardiac-/- mice versus their control littermates, which resulted in a marked reduction in myocardial glucose oxidation and a corresponding increase in palmitate oxidation. This myocardial metabolism profile did not impair systolic function in Pdha1 Cardiac-/- mice, which had comparable left ventricular ejection fractions and fractional shortenings as their αMHC-MerCreMer control littermates, but did produce diastolic dysfunction as seen via the reduced mitral E/A ratio. Therefore, it does appear that forced restriction of glucose oxidation in the hearts of Pdha1 Cardiac-/- mice is sufficient to produce a cardiomyopathy-like phenotype, independent of the perturbed metabolic milieu observed in obesity and/or T2D.

Cardiac function and exercise adaptation in 8 children with LPIN1 mutations.

PubMed

Legendre, Antoine; Khraiche, Diala; Ou, Phalla; Mauvais, François-Xavier; Madrange, Marine; Guemann, Anne-Sophie; Jais, Jean-Philippe; Bonnet, Damien; Hamel, Yamina; de Lonlay, Pascale

2018-03-01

Lipin-1 deficiency is a major cause of rhabdomyolysis that are precipitated by febrile illness. The prognosis is poor, with one-third of patients dying from cardiac arrest during a crisis episode. Apart from acute rhabdomyolysis, most patients are healthy, showing normal clinical and cardiac ultrasound parameters. We report cardiac and exercise examinations of 8 children carrying two LPIN1 mutations. The examinations were performed outside of a myolysis episode, but one patient presented with fever during one examination. All but one patient displayed normal resting cardiac function, as determined by echocardiography. One patient exhibited slight left ventricular dysfunction at rest and a lack of increased stroke volume during cycle ramp exercise. During exercise, peripheral muscle adaptation was impaired in 2 patients compared to healthy controls: they presented an abnormal increase in cardiac output relative to oxygen uptake: dQ/dVO 2 =8.2 and 9.5 (>2DS of controls population). One patient underwent 2 exercise tests; during one test, the patient was febrile, leading to acute rhabdomyolysis in the following hours. He exhibited changes in recovery muscle reoxygenation parameters and an increased dQ/dVO 2 during exercise compared with that under normothermia (7.9 vs 6), which did not lead to acute rhabdomyolysis. The four patients assessed by cardiac 1 H-magnetic resonance spectroscopy exhibited signs of intracardiac steatosis. We observed abnormal haemodynamic profiles during exercise in 3/8 patients with lipin-1 deficiency, suggesting impaired muscle oxidative phosphorylation during exercise. Fever appeared to be an aggravating factor. One patient exhibited moderate cardiac dysfunction, which was possibly related to intracardiac stored lipid toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Extreme respiratory sinus arrhythmia enables overwintering black bear survival--physiological insights and applications to human medicine.

PubMed

Laske, Timothy G; Harlow, Henry J; Garshelis, David L; Iaizzo, Paul A

2010-10-01

American black bears survive winter months without food and water while in a mildly hypothermic, hypometabolic, and inactive state, yet they appear to be able to return to near-normal systemic function within minutes of arousal. This study's goal was to characterize the cardiovascular performance of overwintering black bears and elicit the underlying mechanisms enabling survival. Mid-winter cardiac electrophysiology was assessed in four wild black bears using implanted data recorders. Paired data from early and late winter were collected from 37 wild bears, which were anesthetized and temporarily removed from their dens to record cardiac electrophysiological parameters (12-lead electrocardiograms) and cardiac dimensional changes (echocardiography). Left ventricular thickness, primary cardiac electrophysiological parameters, and cardiovascular response to threats ("fight or flight" response) were preserved throughout winter. Dramatic respiratory sinus arrhythmias were recorded (cardiac cycle length variations up to 865%) with long sinus pauses between breaths (up to 13 s). The accelerated heart rate during breathing efficiently transports oxygen, with the heart "resting" between breaths to minimize energy usage. This adaptive cardiac physiology may have broad implications for human medicine.

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

DOE PAGES

Qian, Fang; Huang, Chao; Lin, Yi-Dong; ...

2017-04-18

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

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

Qian, Fang; Huang, Chao; Lin, Yi-Dong

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

A TASER conducted electrical weapon with cardiac biomonitoring capability: Proof of concept and initial human trial.

PubMed

Stopyra, Jason P; Ritter, Samuel I; Beatty, Jennifer; Johnson, James C; Kleiner, Douglas M; Winslow, James E; Gardner, Alison R; Bozeman, William P

2016-10-01

Despite research demonstrating the overall safety of Conducted Electrical Weapons (CEWs), commonly known by the brand name TASER(®), concerns remain regarding cardiac safety. The addition of cardiac biomonitoring capability to a CEW could prove useful and even lifesaving in the rare event of a medical crisis by detecting and analyzing cardiac rhythms during the period immediately after CEW discharge. To combine an electrocardiogram (ECG) device with a CEW to detect and store ECG signals while still allowing the CEW to perform its primary function of delivering an incapacitating electrical discharge. This work was performed in three phases. In Phase 1 standard law enforcement issue CEW cartridges were modified to demonstrate transmission of ECG signals. In Phase 2, a miniaturized ECG recorder was combined with a standard issue CEW and tested. In Phase 3, a prototype CEW with on-board cardiac biomonitoring was tested on human volunteers to assess its ability to perform its primary function of electrical incapacitation. Bench testing demonstrated that slightly modified CEW cartridge wires transmitted simulated ECG signals produced by an ECG rhythm generator and from a human volunteer. Ultimately, a modified CEW incorporating ECG monitoring successfully delivered incapacitating current to human volunteers and successfully recorded ECG signals from subcutaneous CEW probes after firing. An ECG recording device was successfully incorporated into a standard issue CEW without impeding the functioning of the device. This serves as proof-of-concept that safety measures such as cardiac biomonitoring can be incorporated into CEWs and possibly other law enforcement devices. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

The mechanical coupling of adult marrow stromal stem cells during cardiac regeneration assessed in a 2-D co-culture model

PubMed Central

Valarmathi, Mani T.; Fuseler, John W.; Goodwin, Richard L.; Davis, Jeffrey M.; Potts, Jay D.

2011-01-01

Postnatal cardiomyocytes undergo terminal differentiation and a restricted number of human cardiomyocytes retain the ability to divide and regenerate in response to ischemic injury. However, whether these neo-cardiomyocytes are derived from endogenous population of resident cardiac stem cells or from the exogenous double assurance population of resident bone marrow-derived stem cells that populate the damaged myocardium is unresolved and under intense investigation. The vital challenge is to ameliorate and/or regenerate the damaged myocardium. This can be achieved by stimulating proliferation of native quiescent cardiomyocytes and/or cardiac stem cell, or by recruiting exogenous autologous or allogeneic cells such as fetal or embryonic cardiomyocyte progenitors or bone marrow-derived stromal stem cells. The prerequisites are that these neo-cardiomyocytes must have the ability to integrate well within the native myocardium and must exhibit functional synchronization. Adult bone marrow stromal cells (BMSCs) have been shown to differentiate into cardiomyocyte-like cells both in vitro and in vivo. As a result, BMSCs may potentially play an essential role in cardiac repair and regeneration, but this concept requires further validation. In this report, we have provided compelling evidence that functioning cardiac tissue can be generated by the interaction of multipotent BMSCs with embryonic cardiac myocytes (ECMs) in two-dimensional (2-D) co-cultures. The differentiating BMSCs were induced to undergo cardiomyogenic differentiation pathway and were able to express unequivocal electromechanical coupling and functional synchronization with ECMs. Our 2-D co-culture system provides a useful in vitro model to elucidate various molecular mechanisms underpinning the integration and orderly maturation and differentiation of BMSCs into neo-cardiomyocytes during myocardial repair and regeneration. PMID:21288568

Obesity Alters Molecular and Functional Cardiac Responses to Ischemia-Reperfusion and Glucagon-Like Peptide-1 Receptor Agonism

PubMed Central

Sassoon, Daniel J; Goodwill, Adam G; Noblet, Jillian N; Conteh, Abass M; Herring, B. Paul; McClintick, Jeanette N; Tune, Johnathan D; Mather, Kieren J

2016-01-01

This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miR) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-min coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca2+ binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion. PMID:27234258

Sudden Cardiac Arrest (SCA) Risk Assessment

MedlinePlus

... HRS Find a Specialist Share Twitter Facebook SCA Risk Assessment Sudden Cardiac Arrest (SCA) occurs abruptly and without ... people of all ages and health conditions. Start Risk Assessment The Sudden Cardiac Arrest (SCA) Risk Assessment Tool ...

Dynamic four-dimensional computed tomography (4D CT) imaging for re-entry risk assessment in re-do sternotomy - first experience.

PubMed

Narayanan, Harish; Viana, Fabiano F; Smith, Julian A; Roumeliotis, Nicholas K; Troupis, Christopher J; Crossett, Marcus P; Troupis, John M

2015-10-01

Repeat cardiac surgeries are well known to have higher rates of complications, one of the important reasons being injuries associated with re-do sternotomy. Routine imaging with CT can help to minimise this risk by pre-operatively assessing the anatomical relation between the sternum and the underlying cardiovascular structures, but is limited by its inability to determine the presence and severity of functional tethering and adhesions between these structures. However, with the evolution of wide area detector MD CT scanners, it is possible to assess the presence of tethering using the dynamic four-dimensional CT (4D CT) imaging technique. Nineteen patients undergoing re-do cardiac surgery were pre-operatively imaged using dynamic 4D CT during regulated respiration. The datasets were assessed in cine mode for presence of differential motion between sternum and underlying cardiovascular structures which indicates lack of significant tethering. Overall, there was excellent correlation between preoperative imaging and intraoperative findings. The technique enabled our surgeons to meticulously plan the procedures and to avoid re-entry related injuries. Our initial experience shows that dynamic 4D CT is useful in risk stratification prior to re-do sternotomy by determining the presence or absence of tethering between sternum and underlying structures based on assessment of differential motion. Furthermore we determined the technique to be superior to non-dynamic assessment of retrocardiac tethering. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Mesenchymal-endothelial-transition contributes to cardiac neovascularization

PubMed Central

Ubil, Eric; Duan, Jinzhu; Pillai, Indulekha C.L.; Rosa-Garrido, Manuel; Wu, Yong; Bargiacchi, Francesca; Lu, Yan; Stanbouly, Seta; Huang, Jie; Rojas, Mauricio; Vondriska, Thomas M.; Stefani, Enrico; Deb, Arjun

2014-01-01

Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal-transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial cell like phenotype after acute ischemic cardiac injury. Fibroblast derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast derived endothelial cells, reduces post infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal to endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial-transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair. PMID:25317562

Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study.

PubMed

Casale, Maddalena; Meloni, Antonella; Filosa, Aldo; Cuccia, Liana; Caruso, Vincenzo; Palazzi, Giovanni; Gamberini, Maria Rita; Pitrolo, Lorella; Putti, Maria Caterina; D'Ascola, Domenico Giuseppe; Casini, Tommaso; Quarta, Antonella; Maggio, Aurelio; Neri, Maria Giovanna; Positano, Vincenzo; Salvatori, Cristina; Toia, Patrizia; Valeri, Gianluca; Midiri, Massimo; Pepe, Alessia

2015-08-01

Cardiovascular magnetic resonance (CMR) plays a key role in the management of thalassemia major patients, but few data are available in pediatric population. This study aims at a retrospective multiparametric CMR assessment of myocardial iron overload, function, and fibrosis in a cohort of pediatric thalassemia major patients. We studied 107 pediatric thalassemia major patients (61 boys, median age 14.4 years). Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. All scans were performed without sedation. The 21.4% of the patients showed a significant myocardial iron overload correlated with lower compliance to chelation therapy (P<0.013). Serum ferritin ≥2000 ng/mL and liver iron concentration ≥14 mg/g/dw were detected as the best threshold for predicting cardiac iron overload (P=0.001 and P<0.0001, respectively). A homogeneous pattern of myocardial iron overload was associated with a negative cardiac remodeling and significant higher liver iron concentration (P<0.0001). Myocardial fibrosis by late gadolinium enhancement was detected in 15.8% of the patients (youngest children 13 years old). It was correlated with significant lower heart T2* values (P=0.022) and negative cardiac remodeling indexes. A pathological magnetic resonance imaging liver iron concentration was found in the 77.6% of the patients. Cardiac damage detectable by a multiparametric CMR approach can occur early in thalassemia major patients. So, the first T2* CMR assessment should be performed as early as feasible without sedation to tailor the chelation treatment. Conversely, late gadolinium enhancement CMR should be postponed in the teenager age. © 2015 American Heart Association, Inc.

Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology (TICAP) trial.

PubMed

Tarui, Suguru; Ishigami, Shuta; Ousaka, Daiki; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2015-11-01

Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS). In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control group with standard care alone. The primary end point was to assess procedural feasibility and safety; the secondary end point was to evaluate cardiac function and heart failure status through 36-month follow-up. No complications, including tumor formation, were reported within 36 months after CDC infusion. Echocardiography showed significantly greater improvement in right ventricular ejection fraction (RVEF) in infants receiving CDCs than in controls at 36 months (+8.0% ± 4.7% vs +2.2% ± 4.3%; P = .03). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P = .04), lower incidence of unplanned catheter interventions (P = .04), and higher weight-for-age z score (P = .02) at 36 months relative to controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 36 months were negatively correlated with age, weight-for-age z score, and RVEF at CDC infusion. Intracoronary CDC infusion after staged procedure in patients with HLHS is safe and improves RVEF, which persists during 36-month follow-up. This therapeutic strategy may enhance somatic growth and reduce incidence of heart failure. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Carotid baroreflex responsiveness in heat-stressed humans

NASA Technical Reports Server (NTRS)

Crandall, C. G.

2000-01-01

The effects of whole body heating on human baroreflex function are relatively unknown. The purpose of this project was to identify whether whole body heating reduces the maximal slope of the carotid baroreflex. In 12 subjects, carotid-vasomotor and carotid-cardiac baroreflex responsiveness were assessed in normothermia and during whole body heating. Whole body heating increased sublingual temperature (from 36.4 +/- 0.1 to 37.4 +/- 0.1 degrees C, P < 0.01) and increased heart rate (from 59 +/- 3 to 83 +/- 3 beats/min, P < 0. 01), whereas mean arterial blood pressure (MAP) was slightly decreased (from 88 +/- 2 to 83 +/- 2 mmHg, P < 0.01). Carotid-vasomotor and carotid-cardiac responsiveness were assessed by identifying the maximal gain of MAP and heart rate to R wave-triggered changes in carotid sinus transmural pressure. Whole body heating significantly decreased the responsiveness of the carotid-vasomotor baroreflex (from -0.20 +/- 0.02 to -0.13 +/- 0.02 mmHg/mmHg, P < 0.01) without altering the responsiveness of the carotid-cardiac baroreflex (from -0.40 +/- 0.05 to -0.36 +/- 0.02 beats x min(-1) x mmHg(-1), P = 0.21). Carotid-vasomotor and carotid-cardiac baroreflex curves were shifted downward and upward, respectively, to accommodate the decrease in blood pressure and increase in heart rate that accompanied the heat stress. Moreover, the operating point of the carotid-cardiac baroreflex was shifted closer to threshold (P = 0.02) by the heat stress. Reduced carotid-vasomotor baroreflex responsiveness, coupled with a reduction in the functional reserve for the carotid baroreflex to increase heart rate during a hypotensive challenge, may contribute to increased susceptibility to orthostatic intolerance during a heat stress.

Serca2a and Na{sup +}/Ca{sup 2+} exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid

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

Nascimento, Andrews Marques do; Lima, Ewelyne Mira

Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt{sub max}, − dP/dt{sub min} and Tau) were assessed in the leftmore » ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na{sup +}/Ca{sup 2+} exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. - Highlights: • ND and resistive exercise enhanced the cardiac function and increased expression of cytosolic calcium regulatory components.« less

Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity.

PubMed

Bakkehaug, Jens Petter; Kildal, Anders Benjamin; Engstad, Erik Torgersen; Boardman, Neoma; Næsheim, Torvind; Rønning, Leif; Aasum, Ellen; Larsen, Terje Steinar; Myrmel, Truls; How, Ole-Jakob

2015-07-01

Omecamtiv mecarbil (OM) is a novel inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation. We hypothesized that a potentially favorable energetic effect of unloading the left ventricle, and thus reduction of wall stress, could be counteracted by the prolonged contraction time and ATP-consumption. Postischemic left ventricular dysfunction was created by repetitive left coronary occlusions in 7 pigs (7 healthy pigs also included). In both groups, systolic ejection time and ejection fraction increased after OM (0.75 mg/kg loading for 10 minutes, followed by 0.5 mg/kg/min continuous infusion). Cardiac efficiency was assessed by relating myocardial oxygen consumption to the cardiac work indices, stroke work, and pressure-volume area. To circumvent potential neurohumoral reflexes, cardiac efficiency was additionally assessed in ex vivo mouse hearts and isolated myocardial mitochondria. OM impaired cardiac efficiency; there was a 31% and 23% increase in unloaded myocardial oxygen consumption in healthy and postischemic pigs, respectively. Also, the oxygen cost of the contractile function was increased by 63% and 46% in healthy and postischemic pigs, respectively. The increased unloaded myocardial oxygen consumption was confirmed in OM-treated mouse hearts and explained by an increased basal metabolic rate. Adding the myosin ATPase inhibitor, 2,3-butanedione monoxide abolished all surplus myocardial oxygen consumption in the OM-treated hearts. Omecamtiv mecarbil, in a clinically relevant model, led to a significant myocardial oxygen wastage related to both the contractile and noncontractile function. This was mediated by that OM induces a continuous activation in resting myosin ATPase. © 2015 American Heart Association, Inc.

Noninvasive pulmonary transit time: A new parameter for general cardiac performance.

PubMed

de Lepper, Anouk G W; Herold, Ingeborg H F; Saporito, Salvatore; Bouwman, R Arthur; Mischi, Massimo; Korsten, Hendrikus H M; Reesink, Koen D; Houthuizen, Patrick

2017-08-01

Pulmonary transit time (PTT) assessed with contrast-enhanced ultrasound (CEUS) is a novel tool to evaluate cardiac function. PTT represents the time for a bolus of contrast to pass from the right to the left ventricle, measured according to the indicator dilution principles using CEUS. We investigated the hypothesis that PTT is a measure of general cardiac performance in patient populations eligible for cardiac resynchronization therapy (CRT). The study population consisted of heart failure patients referred for CRT with NYHA class II-IV, left ventricular ejection fraction (LVEF)≤35% and QRS≥120 ms. CEUS, ECG, and blood were analyzed, and participants completed a quality of life questionnaire at baseline and 3 months after CRT implantation. Normalized PTT (nPTT) was calculated to compensate for the heart rate. Correlations were assessed with Pearson's or Spearman's coefficients and stratified for rhythm and NYHA class. The study population consisted of 94 patients (67 men) with a mean age of 70±8.9 years. (n)PTT was significantly correlated with left ventricular parameters (r s =-.487, P<.001), right ventricular parameters (r=-.282, P=.004), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r s =.475, P<.001), and quality of life (r s =.364, P<.001). Stronger significant correlations were found in patients in sinus rhythm. CEUS-derived PTT and nPTT correlate to a fair degree with measures of systolic and diastolic function, NT-pro-BNP, and quality of life. As CEUS-derived PTT can be obtained easily, noninvasively and at the bedside, it is a promising future measure of general cardiac performance. © 2017, Wiley Periodicals, Inc.

Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase

PubMed Central

Ussher, John R.; Koves, Timothy R.; Jaswal, Jagdip S.; Zhang, Liyan; Ilkayeva, Olga; Dyck, Jason R.B.; Muoio, Deborah M.; Lopaschuk, Gary D.

2009-01-01

OBJECTIVE Whereas an impaired ability to oxidize fatty acids is thought to contribute to intracellular lipid accumulation, insulin resistance, and cardiac dysfunction, high rates of fatty acid oxidation could also impair glucose metabolism and function. We therefore determined the effects of diet-induced obesity (DIO) in wild-type (WT) mice and mice deficient for malonyl CoA decarboxylase (MCD−/−; an enzyme promoting mitochondrial fatty acid oxidation) on insulin-sensitive cardiac glucose oxidation. RESEARCH DESIGN AND METHODS WT and MCD−/− mice were fed a low- or high-fat diet for 12 weeks, and intramyocardial lipid metabolite accumulation was assessed. A parallel feeding study was performed to assess myocardial function and energy metabolism (nanomoles per gram of dry weight per minute) in isolated working hearts (+/– insulin). RESULTS DIO markedly reduced insulin-stimulated glucose oxidation compared with low fat–fed WT mice (167 ± 31 vs. 734 ± 125; P < 0.05). MCD−/− mice subjected to DIO displayed a more robust insulin-stimulated glucose oxidation (554 ± 82 vs. 167 ± 31; P < 0.05) and less incomplete fatty acid oxidation, evidenced by a decrease in long-chain acylcarnitines compared with WT counterparts. MCD−/− mice had long-chain acyl CoAs similar to those of WT mice subjected to DIO but had increased triacylglycerol levels (10.92 ± 3.72 vs. 3.29 ± 0.62 μmol/g wet wt; P < 0.05). CONCLUSIONS DIO does not impair cardiac fatty acid oxidation or function, and there exists disassociation between myocardial lipid accumulation and insulin sensitivity. Our results suggest that MCD deficiency is not detrimental to the heart in obesity. PMID:19478144

Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

PubMed

Gao, Jun-Qing; Xie, Yun; Yang, Wei; Zheng, Jian-Pu; Liu, Zong-Jun

2017-01-01

Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

The relation of red blood cell fatty acids with vascular stiffness, cardiac structure and left ventricular function: the Framingham Heart Study.

PubMed

Kaess, Bernhard M; Harris, William S; Lacey, Sean; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Robins, Sander J; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

2015-02-01

Polyunsaturated fatty acids have been associated with beneficial influences on cardiovascular health. However, the underlying mechanisms are not clear, and data on the relations of polyunsaturated fatty acids to subclinical disease measures such as vascular stiffness and cardiac function are sparse and inconclusive. In a large community-based cohort, we examined the relations of omega-3 and other fatty acids to a comprehensive panel of vascular function measures (assessing microvascular function and large artery stiffness), cardiac structure and left ventricular function. Red blood cell (RBC) membrane fatty acid composition, a measure of long-term fatty acid intake, was assessed in participants of the Framingham Offspring Study and Omni cohorts and related to tonometry-derived measures of vascular stiffness and to a panel of echocardiographic traits using partial correlations. Up to n=3055 individuals (56% women, mean age 66 years) were available for analyses. In age- and sex-adjusted models, higher RBC omega-3 content was moderately associated (p≤0.002) with several measures of vascular stiffness and function in a protective direction. However, after multivariable adjustment, only an association of higher RBC omega-3 content with lower carotid-femoral pulse wave velocity (a measure of aortic stiffness) remained significant (r = -0.06, p=0.002). In secondary analyses, higher linoleic acid, the major nutritional omega-6 fatty acid, was associated with smaller left atrial size, even after multivariable adjustment (r = -0.064, p<0.001). In conclusion, in our cross-sectional community-based study, we found several associations consistent with the notion of protective effects of omega-3 and linoleic acid. The clinical significance of these modest associations remains to be elucidated. © The Author(s) 2014.

Prognostic role of cardiac power index in ambulatory patients with advanced heart failure.

PubMed

Grodin, Justin L; Mullens, Wilfried; Dupont, Matthias; Wu, Yuping; Taylor, David O; Starling, Randall C; Tang, W H Wilson

2015-07-01

Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (<0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P < 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

The Potential of Clinical Phenotyping of Heart Failure With Imaging Biomarkers for Guiding Therapies: A Focused Update.

PubMed

Sengupta, Partho P; Kramer, Christopher M; Narula, Jagat; Dilsizian, Vasken

2017-09-01

The need for noninvasive assessment of cardiac volumes and ejection fraction (EF) ushered in the use of cardiac imaging techniques in heart failure (HF) trials that investigated the roles of pharmacological and device-based therapies. However, in contrast to HF with reduced EF (HFrEF), modern HF pharmacotherapy has not improved outcomes in HF with preserved EF (HFpEF), largely attributed to patient heterogeneity and incomplete understanding of pathophysiological insights underlying the clinical presentations of HFpEF. Modern cardiac imaging methods offer insights into many sets of changes in cardiac tissue structure and function that can precisely link cause with cardiac remodeling at organ and tissue levels to clinical presentations in HF. This has inspired investigators to seek a more comprehensive understanding of HF presentations using imaging techniques. This article summarizes the available evidence regarding the role of cardiac imaging in HF. Furthermore, we discuss the value of cardiac imaging techniques in identifying HF patient subtypes who share similar causes and mechanistic pathways that can be targeted using specific HF therapies. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Assessment of myocardial fibrosis with T1 mapping MRI.

PubMed

Everett, R J; Stirrat, C G; Semple, S I R; Newby, D E; Dweck, M R; Mirsadraee, S

2016-08-01

Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

42 CFR 410.49 - Cardiac rehabilitation program and intensive cardiac rehabilitation program: Conditions of coverage.

Code of Federal Regulations, 2011 CFR

2011-10-01

... prescribed exercise, cardiac risk factor modification, psychosocial assessment, and outcomes assessment... rehabilitation items and services are furnished. (ii) Cardiac risk factor modification, including education...

N-terminal pro-brain natriuretic peptide and abnormal brain aging: The AGES-Reykjavik Study.

PubMed

Sabayan, Behnam; van Buchem, Mark A; de Craen, Anton J M; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

2015-09-01

To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p < 0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. © 2015 American Academy of Neurology.

An in silico framework to analyze the anisotropic shear wave mechanics in cardiac shear wave elastography

NASA Astrophysics Data System (ADS)

Caenen, Annette; Pernot, Mathieu; Peirlinck, Mathias; Mertens, Luc; Swillens, Abigail; Segers, Patrick

2018-04-01

Shear wave elastography (SWE) is a potential tool to non-invasively assess cardiac muscle stiffness. This study focused on the effect of the orthotropic material properties and mechanical loading on the performance of cardiac SWE, as it is known that these factors contribute to complex 3D anisotropic shear wave propagation. To investigate the specific impact of these complexities, we constructed a finite element model with an orthotropic material law subjected to different uniaxial stretches to simulate SWE in the stressed cardiac wall. Group and phase speed were analyzed in function of tissue thickness and virtual probe rotation angle. Tissue stretching increased the group and phase speed of the simulated shear wave, especially in the direction of the muscle fiber. As the model provided access to the true fiber orientation and material properties, we assessed the accuracy of two fiber orientation extraction methods based on SWE. We found a higher accuracy (but lower robustness) when extracting fiber orientations based on the location of maximal shear wave speed instead of the angle of the major axis of the ellipsoidal group speed surface. Both methods had a comparable performance for the center region of the cardiac wall, and performed less well towards the edges. Lastly, we also assessed the (theoretical) impact of pathology on shear wave physics and characterization in the model. It was found that SWE was able to detect changes in fiber orientation and material characteristics, potentially associated with cardiac pathologies such as myocardial fibrosis. Furthermore, the model showed clearly altered shear wave patterns for the fibrotic myocardium compared to the healthy myocardium, which forms an initial but promising outcome of this modeling study.

Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration

PubMed Central

Symington, Burger; Mapanga, Rudo F.; Norton, Gavin R.

2017-01-01

Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail. PMID:28107484

The role of exercise testing in heart failure.

PubMed

Swedberg, K; Gundersen, T

1993-01-01

The objectives of exercise testing in congestive heart failure (CHF) may be summarized as follows: (a) detect impaired cardiac performance, (b) grade severity of cardiac failure and classify functional capability, and (c) assess effects of interventions. Several different methods are available to make these assessments, and we have to ask ourselves how well exercise testing achieves these objectives. It has to be kept in mind that the power generated by the exercising muscles is dependent on the oxygen delivery to the skeletal muscles. Oxygen uptake is the result of an integrated performance of the lungs, heart, and peripheral circulation. In patients, as well as in normal subjects, oxygen uptake is related to hemodynamic indices such as cardiac output, stroke volume, or exercise duration when a stepwise regulated maximal exercise protocol is used. However, there are major differences in the concept of a true maximum in normal subjects versus heart failure patients. Fit-normal subjects will achieve a real maximal oxygen uptake, whereas patients may stop testing before a maximum is reached because of symptoms such as dyspnea or leg fatigue. Therefore, it is better if the actual oxygen uptake can be measured. "Peak" rather than true maximal oxygen uptake has been suggested for the classification of the severity of heart failure. Peripheral factors modify the cardiac output through such factors as vascular resistance, organ function, and hormonal release. Maximal exercise will stress the cardiovascular system to a point where the weakest chain will impose a limiting effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystatin C and Cardiac Measures in Children and Adolescents With CKD.

PubMed

Brady, Tammy M; Townsend, Kelly; Schneider, Michael F; Cox, Christopher; Kimball, Thomas; Madueme, Peace; Warady, Bradley; Furth, Susan; Mitsnefes, Mark

2017-02-01

Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function. Prospective cohort study. 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. Serum cystatin C (mg/L) measured annually. Cardiac structure (left ventricular mass index [g/m 2.7 ]) and cardiac function (shortening fraction; E/A, E'/A', E/E' ratios) measured every other year. Demographics and anthropometrics, measured glomerular filtration rate (mGFR), heart rate, blood pressure, hemoglobin z score, serum albumin level, and calcium-phosphorus product. Independent of time, each 1-mg/L increase in cystatin C level was independently associated with a concurrent 7.7% (95% CI, 5.3%-10.0%) increase in left ventricular mass index, a -4.7% (95% CI, -7.0% to -2.4%) change in E/A ratio, a -6.6% (95% CI, -9.0% to -4.2%) change in E'/A' ratio, and a 2.5% (95% CI, 0.3%-4.7%) increase in E/E' ratio. mGFR was also independently associated with E'/A' ratio. When cystatin C level and mGFR were included in the same model, cystatin C level remained independently associated with E'/A' ratio, whereas mGFR was not. 24% of the cohort was missing data for outcomes of interest or measurements; study population includes only children and adolescents with mild to moderate CKD. In this study of children and adolescents with mild to moderate CKD, cystatin C level was independently associated with cardiac structure and diastolic function. Cystatin C level remained able to predict diastolic function decline via E'/A' ratio even after adjusting for mGFR, suggesting that cystatin C level may have an independent role in CVD risk stratification among children and adolescents with CKD. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Exposure of the developing heart to diabetic environment and early cardiac assessment: A review.

PubMed

Asoglu, Mehmet R; Gabbay-Benziv, Rinat; Turan, Ozhan M; Turan, Sifa

2018-02-01

Hyperglycemia during organogenesis is associated with an increased risk of congenital cardiac defects (CHDs). The pathophysiology leading to CHDs is not completely uncovered. However, elevated oxidative stress is considered to be the primary trigger that causes CHDs in fetuses of diabetic mothers. Maternal diabetes has been found to increase the risk for all types of CHDs. Diabetes may also impact the fetal cardiac performance at all gestational ages. Early detection of CHDs has certain advantages, such as making early decision about termination of pregnancy, enabling early genetic testing, and early reassurance if scan is normal. Combined transabdominal and transvaginal approach at 13-14 weeks of gestation is a reasonable strategy to assess fetal heart in diabetic women. Diagnostic accuracy of early fetal echocardiography has reached to above a reasonable cutoff when it is done in the late first trimester or early second trimester in the hands of expert sonographers. However, the literature is less certain to provide a firm conclusion about functional heart assessment in fetuses of diabetic mothers. © 2018 Wiley Periodicals, Inc.

Adaptive servo-ventilation for central sleep apnoea in systolic heart failure: results of the major substudy of SERVE-HF.

PubMed

Cowie, Martin R; Woehrle, Holger; Wegscheider, Karl; Vettorazzi, Eik; Lezius, Susanne; Koenig, Wolfgang; Weidemann, Frank; Smith, Gillian; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita K; Somers, Virend K; Zannad, Faiez; Teschler, Helmut

2018-03-01

The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers. In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months. In secondary analyses, data for patients with baseline and 12-month values were evaluated; 312 patients participated in the substudy. The primary endpoint, change in echocardiographically determined left ventricular ejection fraction from baseline to 12 months, did not differ significantly between the ASV and the control groups. There were also no significant between-group differences for changes in left ventricular dimensions, wall thickness, diastolic function or right ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in small patient numbers). Plasma N-terminal pro B-type natriuretic peptide concentration decreased in both groups, and values were similar at 12 months. There were no significant between-group differences in changes in cardiac, renal and systemic inflammation biomarkers. In patients with systolic heart failure and CSA, addition of ASV to guideline-based medical management had no statistically significant effect on cardiac structure and function, or on cardiac biomarkers, renal function and systemic inflammation over 12 months. The increased cardiovascular mortality reported in SERVE-HF may not be related to adverse remodelling or worsening heart failure. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis

PubMed Central

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis. PMID:29161313

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

PubMed

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You; Chu, Chun-Lin

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study

PubMed Central

Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

2014-01-01

Background: Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. Objectives: The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Methods: Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism. Results: Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Conclusion: Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism. PMID:25093618

Right ventricular dysfunction after resuscitation predicts poor outcomes in cardiac arrest patients independent of left ventricular function.

PubMed

Ramjee, Vimal; Grossestreuer, Anne V; Yao, Yuan; Perman, Sarah M; Leary, Marion; Kirkpatrick, James N; Forfia, Paul R; Kolansky, Daniel M; Abella, Benjamin S; Gaieski, David F

2015-11-01

Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction. A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012. 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous circulation (ROSC) and post-arrest echocardiograms. Of the 291 patients, 57% were male, with a mean age of 59 ± 16 years. 179 (63%) patients had LV dysfunction, 173 (59%) had RV dysfunction, and 124 (44%) had biventricular dysfunction on the initial post-arrest echocardiogram. Independent of LV function, RV dysfunction was predictive of worse survival (mild or moderate: OR 0.51, CI 0.26-0.99, p<0.05; severe: OR 0.19, CI 0.06-0.65, p=0.008) and neurologic outcome (mild or moderate: OR 0.33, CI 0.17-0.65, p=0.001; severe: OR 0.11, CI 0.02-0.50, p=0.005) compared to patients with normal RV function after cardiac arrest. Echocardiographic findings of post-arrest RV dysfunction were equally prevalent as LV dysfunction. RV dysfunction was significantly predictive of worse outcomes in post-arrest patients after accounting for LV dysfunction. Post-arrest RV dysfunction may be useful for risk stratification and management in this high-mortality population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The heart and potassium: a banana republic.

PubMed

Khan, Ehsan; Spiers, Christine; Khan, Maria

2013-03-01

The importance of potassium in maintaining stable cardiac function is a clinically understood phenomenon. Physiologically the importance of potassium in cardiac function is described by the large number of different kinds of potassium ions channels found in the heart compared to channels and membrane transport mechanisms for other ions such as sodium and calcium. Potassium is important in physiological homeostatic control of cardiac function, but is also of relevance to the diseased state, as potassium-related effects may stabilize or destabilize cardiac function. This article aims to provide a detailed understanding of potassium-mediated cardiac function. This will help the clinical practitioner evaluate how modulation of potassium ion channels by disease and pharmacological manipulation affect the cardiac patient, thus aiding in decision making when faced with clinical problems related to potassium.

Extra-cardiac findings in cardiovascular magnetic resonance: what the imaging cardiologist needs to know.

PubMed

Rodrigues, Jonathan C L; Lyen, Stephen M; Loughborough, William; Amadu, Antonio Matteo; Baritussio, Anna; Dastidar, Amardeep Ghosh; Manghat, Nathan E; Bucciarelli-Ducci, Chiara

2016-05-09

Cardiovascular magnetic resonance (CMR) is an established non-invasive technique to comprehensively assess cardiovascular structure and function in a variety of acquired and inherited cardiac conditions. A significant amount of the neck, thorax and upper abdomen are imaged at the time of routine clinical CMR, particularly in the initial multi-slice axial and coronal images. The discovery of unsuspected disease at the time of imaging has ethical, financial and medico-legal implications. Extra-cardiac findings at the time of CMR are common, can be important and can change clinical management. Certain patient groups undergoing CMR are at particular risk of important extra-cardiac findings as several of the cardiovascular risk factors for atherosclerosis are also risk factors for malignancy. Furthermore, the presence of certain extra-cardiac findings may contribute to the interpretation of the primary cardiac pathology as some cardiac conditions have multi-systemic extra-cardiac involvement. The aim of this review is to give an overview of the type of extra-cardiac findings that may become apparent on CMR, subdivided by anatomical location. We focus on normal variant anatomy that may mimic disease, common incidental extra-cardiac findings and important imaging signs that help distinguish sinister pathology from benign disease. We also aim to provide a framework to the approach and potential further diagnostic work-up of incidental extra-cardiac findings discovered at the time of CMR. However, it is beyond the scope of this review to discuss and determine the clinical significance of extracardiac findings at CMR.

Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.

PubMed

Kim, S Y; Montoya, A; Zbilut, J P; Mawulawde, K; Sullivan, H J; Lonchyna, V A; Terrell, M R; Pifarré, R

1996-02-01

Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.

Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction.

PubMed

Wang, Jiaxing; Lu, Songhe; Zheng, Qijun; Hu, Nan; Yu, Wenjun; Li, Na; Liu, Min; Gao, Beilei; Zhang, Guoyong; Zhang, Yingmei; Wang, Haichang

2016-07-01

Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteins for biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage.

Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function.

PubMed

Hurwitz, Barry E; Coryell, Virginia T; Parker, Meela; Martin, Pedro; Laperriere, Arthur; Klimas, Nancy G; Sfakianakis, George N; Bilsker, Martin S

2009-10-19

The study examined whether deficits in cardiac output and blood volume in a CFS (chronic fatigue syndrome) cohort were present and linked to illness severity and sedentary lifestyle. Follow-up analyses assessed whether differences in cardiac output levels between CFS and control groups were corrected by controlling for cardiac contractility and TBV (total blood volume). The 146 participants were subdivided into two CFS groups based on symptom severity data, severe (n=30) and non-severe (n=26), and two healthy non-CFS control groups based on physical activity, sedentary (n=58) and non-sedentary (n=32). Controls were matched to CFS participants using age, gender, ethnicity and body mass. Echocardiographic measures indicated that the severe CFS participants had 10.2% lower cardiac volume (i.e. stroke index and end-diastolic volume) and 25.1% lower contractility (velocity of circumferential shortening corrected by heart rate) than the control groups. Dual tag blood volume assessments indicated that the CFS groups had lower TBV, PV (plasma volume) and RBCV (red blood cell volume) than control groups. Of the CFS subjects with a TBV deficit (i.e. > or = 8% below ideal levels), the mean+/-S.D. percentage deficit in TBV, PV and RBCV were -15.4+/-4.0, -13.2+/-5.0 and -19.1+/-6.3% respectively. Lower cardiac volume levels in CFS were substantially corrected by controlling for prevailing TBV deficits, but were not affected by controlling for cardiac contractility levels. Analyses indicated that the TBV deficit explained 91-94% of the group differences in cardiac volume indices. Group differences in cardiac structure were offsetting and, hence, no differences emerged for left ventricular mass index. Therefore the findings indicate that lower cardiac volume levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac contractility levels, but were probably a consequence of a co-morbid hypovolaemic condition. Further study is needed to address the extent to which the cardiac and blood volume alterations in CFS have physiological and clinical significance.

Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease.

PubMed

Kuczmarski, James M; Martens, Christopher R; Kim, Jahyun; Lennon-Edwards, Shannon L; Edwards, David G

2014-09-01

The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 ± 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO. Copyright © 2014 the American Physiological Society.

Xenon for the prevention of postoperative delirium in cardiac surgery: study protocol for a randomized controlled clinical trial.

PubMed

Al Tmimi, Layth; Van de Velde, Marc; Herijgers, Paul; Meyns, Bart; Meyfroidt, Geert; Milisen, Koen; Fieuws, Steffen; Coburn, Mark; Poesen, Koen; Rex, Steffen

2015-10-09

Postoperative delirium (POD) is a manifestation of acute postoperative brain dysfunction that is frequently observed after cardiac surgery. POD is associated with short-term complications such as an increase in mortality, morbidity, costs and length of stay, but can also have long-term sequelae, including persistent cognitive deficits, loss of independence, and increased mortality for up to 2 years. The noble gas xenon has been demonstrated in various models of neuronal injury to exhibit remarkable neuroprotective properties. We therefore hypothesize that xenon anesthesia reduces the incidence of POD in elderly patients undergoing cardiac surgery with the use of cardiopulmonary bypass. One hundred and ninety patients, older than 65 years, and scheduled for elective cardiac surgery, will be enrolled in this prospective, randomized, controlled trial. Patients will be randomized to receive general anesthesia with either xenon or sevoflurane. Primary outcome parameter will be the incidence of POD in the first 5 postoperative days. The occurrence of POD will be assessed by trained research personnel, blinded to study group, with the validated 3-minute Diagnostic Confusion Assessment Method (3D-CAM) (on the intensive care unit in its version specifically adapted for the ICU), in addition to chart review and the results of delirium screening tools that will be performed by the bedside nurses). Secondary outcome parameters include duration and severity of POD, and postoperative cognitive function as assessed with the Mini-Mental State Examination. Older patients undergoing cardiac surgery are at particular risk to develop POD. Xenon provides remarkable hemodynamic stability and has been suggested in preclinical studies to exhibit neuroprotective properties. The present trial will assess whether the promising profile of xenon can be translated into a better outcome in the geriatric population. EudraCT Identifier: 2014-005370-11 (13 May 2015).

Right ventricle functional parameters estimation in arrhythmogenic right ventricular dysplasia using a robust shape based deformable model.

PubMed

Oghli, Mostafa Ghelich; Dehlaghi, Vahab; Zadeh, Ali Mohammad; Fallahi, Alireza; Pooyan, Mohammad

2014-07-01

Assessment of cardiac right-ventricle functions plays an essential role in diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). Among clinical tests, cardiac magnetic resonance imaging (MRI) is now becoming the most valid imaging technique to diagnose ARVD. Fatty infiltration of the right ventricular free wall can be visible on cardiac MRI. Finding right-ventricle functional parameters from cardiac MRI images contains segmentation of right-ventricle in each slice of end diastole and end systole phases of cardiac cycle and calculation of end diastolic and end systolic volume and furthermore other functional parameters. The main problem of this task is the segmentation part. We used a robust method based on deformable model that uses shape information for segmentation of right-ventricle in short axis MRI images. After segmentation of right-ventricle from base to apex in end diastole and end systole phases of cardiac cycle, volume of right-ventricle in these phases calculated and then, ejection fraction calculated. We performed a quantitative evaluation of clinical cardiac parameters derived from the automatic segmentation by comparison against a manual delineation of the ventricles. The manually and automatically determined quantitative clinical parameters were statistically compared by means of linear regression. This fits a line to the data such that the root-mean-square error (RMSE) of the residuals is minimized. The results show low RMSE for Right Ventricle Ejection Fraction and Volume (≤ 0.06 for RV EF, and ≤ 10 mL for RV volume). Evaluation of segmentation results is also done by means of four statistical measures including sensitivity, specificity, similarity index and Jaccard index. The average value of similarity index is 86.87%. The Jaccard index mean value is 83.85% which shows a good accuracy of segmentation. The average of sensitivity is 93.9% and mean value of the specificity is 89.45%. These results show the reliability of proposed method in these cases that manual segmentation is inapplicable. Huge shape variety of right-ventricle led us to use a shape prior based method and this work can develop by four-dimensional processing for determining the first ventricular slices.

Cardiovascular Magnetic Resonance and prognosis in cardiac amyloidosis

PubMed Central

Maceira, Alicia M; Prasad, Sanjay K; Hawkins, Philip N; Roughton, Michael; Pennell, Dudley J

2008-01-01

Background Cardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR) can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE) and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study. Materials and methods The pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE). Results Patients with were followed for a median of 623 days (IQ range 221, 1436), during which 17 (58%) patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis). Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205). Conclusion In cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden. PMID:19032744

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

2009-01-01

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

Myocardin-related transcription factors are required for cardiac development and function

PubMed Central

Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

2016-01-01

Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

Prospective study of tricuspid valve regurgitation associated with permanent leads in patients undergoing cardiac rhythm device implantation: Background, rationale, and design

PubMed Central

Dokainish, Hisham; Elbarasi, Esam; Masiero, Simona; Van de Heyning, Caroline; Brambatti, Michela; Ghazal, Sami; AL-Maashani, Said; Capucci, Alessandro; Buikema, Lisanne; Leong, Darryl; Shivalkar, Bharati; Saenen, Johan; Miljoen, Hielko; Morillo, Carlos; Divarakarmenon, Syam; Amit, Guy; Ribas, Sebastian; Brautigam, Aaron; Baiocco, Erika; Maolo, Alessandro; Romandini, Andrea; Maffei, Simone; Connolly, Stuart; Healey, Jeff

2015-01-01

Given the increasing numbers of cardiac device implantations worldwide, it is important to determine whether permanent endocardial leads across the tricuspid valve can promote tricuspid regurgitation (TR). Virtually all current data is retrospective, and indicates a signal of TR being increased after permanent lead implantation. However, the precise incidence of moderate or greater TR post-procedure, the exact mechanisms (mechanical, traumatic, functional), and the hemodynamic burden and clinical effects of this putative increase in TR, remain uncertain. We have therefore designed a multicenter, international, prospective study of 300 consecutive patients (recruitment completed, baseline data presented) who will undergo echocardiography and clinical assessment prior to, and at 1-year post device insertion. This prospective study will help determine whether cardiac device-associated TR is real, what are its potential mechanisms, and whether it has an important clinical impact on cardiac device patients. PMID:26779517

[What should we know about cardiac amyloidosis? From clinical signs to treatment].

PubMed

Földeák, Dóra; Nemes, Attila; Kalapos, Anita; Domsik, Péter; Kormányos, Árpád; Krenács, László; Bagdi, Enikő; Borbényi, Zita

2017-11-01

Systemic amyloidosis is a rare disease, in which the heart involvement is rather frequent and determines survival remarkably. Regarding the disease and organ involvement, new diagnostic procedures help to establish the diagnosis and to start the adequate treatment as soon as possible. Cardiac involvement is more likely to be characterised by monoclonal immunglobulin free light chain (AL amyloidosis) type and transthyretin type. In case of AL amyloidosis, heart involvement can lead to serious consequences. Biomarker assessments for cardiac function are important to determine disease severity at the beginning and to measure response to the treatment. In case of amyloidosis, the incidence of the heart involvement grows with age. The prevalence is not known exactly, but probably there are more cases than recognised. The authors present the clinical signs and diagnostic methods, emphasizing the importance of the cardiac examination methods. Orv Hetil. 2017; 158(46): 1811-1818.

Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid.

PubMed

Li, Chun-jun; Lv, Lin; Li, Hui; Yu, De-min

2012-06-19

Alpha-lipoic acid (ALA), a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM) has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS), extracellular matrix (ECM) remodeling and interrelated signaling pathways in a diabetic rat model. Diabetes was induced in rats by I.V. injection of streptozotocin (STZ) at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen) was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2) levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β). Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK), p38 MAPK and ERK were also assayed by Western blot. DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated signaling pathway components were evaluated. It was shown that redox homeostasis was disturbed and MAPK signaling pathway components activated in STZ-induced DCM animals. While ALA treatment favorably shifted redox homeostasis and suppressed JNK and p38 MAPK activation. These results, coupled with the excellent safety and tolerability profile of ALA in humans, demonstrate that ALA may have therapeutic potential in the treatment of DCM by attenuating MOS, ECM remodeling and JNK, p38 MAPK activation.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

PubMed

Wilson, K S; Baily, J; Tucker, C S; Matrone, G; Vass, S; Moran, C; Chapman, K E; Mullins, J J; Kenyon, C; Hadoke, P W F; Denvir, M A

2015-10-15

Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Prognostic value of echocardiographic indices of left atrial morphology and function in dogs with myxomatous mitral valve disease.

PubMed

Baron Toaldo, Marco; Romito, Giovanni; Guglielmini, Carlo; Diana, Alessia; Pelle, Nazzareno G; Contiero, Barbara; Cipone, Mario

2018-05-01

The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). One-hundred and fifteen dogs of different breeds with MMVD. Prospective cohort study. Conventional morphologic and echo-Doppler variables, LA areas and volumes, and STE-based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac-related death. Most of the tested variables, including all LA STE-derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76-11.24; P < .001) and LAVmax (HR, 2.32; CI, 1.10-4.89; P = .024) remained statistically significant in the multivariable analysis. The assessment of LA dimension and function provides useful prognostic information in dogs with MMVD. Considering all the LA variables, LAVmax appears the strongest predictor of cardiac death, being superior to LA/Ao and STE-derived variables. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Reference ranges of left ventricular structure and function assessed by contrast-enhanced cardiac MR and changes related to ageing and hypertension in a population-based study.

PubMed

Bülow, Robin; Ittermann, Till; Dörr, Marcus; Poesch, Axel; Langner, Sönke; Völzke, Henry; Hosten, Norbert; Dewey, Marc

2018-03-14

Reference ranges of left ventricular (LV) parameters from cardiac magnetic resonance (CMR) were established to investigate the impact of ageing and hypertension as important determinants of cardiac structure and function. One thousand five hundred twenty-five contrast-enhanced CMRs were conducted in the Study of Health in Pomerania. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), ejection fraction (LVEF), and myocardial mass (LVMM) were determined using long- and short-axis steady-state free-precession sequences. The reference population was defined as participants without late enhancement, hypertension, and prior cardiovascular diseases. Reference ranges were established by quantile regression (5th and 95th percentile) and compared with an additional sample of treated and untreated hypertensives. LV volumes in the reference population (n = 634, 300 males, 334 females, 52.1 ± 13.3 years) aged between 20-69 years were lower with higher age (p = 0.001), whereas LVEFs were higher (p ≤ 0.020). LVMM was lower only in males (p = 0.002). Compared with the reference population, hypertension was associated with lower LVEDV in males (n = 258, p ≤ 0.032). Antihypertensive therapy was associated with higher LVEF in males (n = 258, +2.5%, p = 0.002) and females (n = 180, +2.1%, p = 0.001). Population-based LV reference ranges were derived from contrast-enhanced CMR. Hypertension-related changes were identified by comparing these values with those of hypertensives, and they might be used to monitor cardiac function in these patients. • Left ventricular function changed slightly but significantly between 20-69 years. • Reference values of BSA-indexed myocardial mass decreased with age in males. • Hypertension was associated with lower LV end-diastolic volume only in males. • CMR may allow assessing remodelling related to hypertension or antihypertensive treatment.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart

PubMed Central

Wilson, K.S.; Baily, J.; Tucker, C.S.; Matrone, G.; Vass, S.; Moran, C.; Chapman, K.E.; Mullins, J.J.; Kenyon, C.; Hadoke, P.W.F.; Denvir, M.A.

2015-01-01

Background Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Methods and results Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Conclusion Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. PMID:26219824

IFATS Collection: Human Adipose Tissue-Derived Stem Cells Induce Angiogenesis and Nerve Sprouting Following Myocardial Infarction, in Conjunction with Potent Preservation of Cardiac Function

PubMed Central

Cai, Liying; Johnstone, Brian H.; Cook, Todd G.; Tan, Jian; Fishbein, Michael C.; Chen, Peng-Sheng; March, Keith L.

2010-01-01

The administration of therapeutic cell types, such as stem and progenitor cells, has gained much interest for the limitation or repair of tissue damage caused by a variety of insults. However, it is still uncertain whether the morphological and functional benefits are mediated predominantly via cell differentiation or paracrine mechanisms. Here, we assessed the extent and mechanisms of adipose-derived stromal/stem cells (ASC)-dependent tissue repair in the context of acute myocardial infarction. Human ASCs in saline or saline alone was injected into the peri-infarct region in athymic rats following left anterior descending (LAD) coronary artery ligation. Cardiac function and structure were evaluated by serial echocardiography and histology. ASC-treated rats consistently exhibited better cardiac function, by all measures, than control rats 1 month following LAD occlusion. Left ventricular (LV) ejection fraction and fractional shortening were improved in the ASC group, whereas LV remodeling and dilation were limited in the ASC group compared with the saline control group. Anterior wall thinning was also attenuated by ASC treatment, and post-mortem histological analysis demonstrated reduced fibrosis in ASC-treated hearts, as well as increased peri-infarct density of both arterioles and nerve sprouts. Human ASCs were persistent at 1 month in the peri-infarct region, but they were not observed to exhibit significant cardiomyocyte differentiation. Human ASCs preserve heart function and augment local angiogenesis and cardiac nerve sprouting following myocardial infarction predominantly by the provision of beneficial trophic factors. PMID:18772313

Randomised controlled trial examining the effect of an outpatient exercise training programme on haemodynamics and cardiac MR parameters of right ventricular function in patients with pulmonary arterial hypertension: the ExPAH study protocol.

PubMed

Chia, Karen S W; Faux, Steven G; Wong, Peter K K; Holloway, Cameron; Assareh, Hassan; McLachlan, Craig S; Kotlyar, Eugene

2017-02-06

Pulmonary hypertension (PH) is a potentially life-threatening condition characterised by elevated pulmonary artery pressure. Early stage PH patients are often asymptomatic. Disease progression is associated with impairment of right ventricular function and progressive dyspnoea. Current guidelines recommend exercise training (grade IIa, level B). However, many questions remain regarding the mechanisms of improvement, intensity of supervision and optimal frequency, duration and intensity of exercise. This study will assess the effect of an outpatient rehabilitation programme on haemodynamics and cardiac right ventricular function in patients with pulmonary arterial hypertension (PAH), a subgroup of PH. This randomised controlled trial involves both a major urban tertiary and smaller regional hospital in New South Wales, Australia. The intervention will compare an outpatient rehabilitation programme with a control group (home exercise programme). Participants will be stable on oral PAH-specific therapy. The primary outcome measure will be right ventricular ejection fraction measured by cardiac MRI. Secondary outcomes will include haemodynamics measured by right heart catheterisation, endurance, functional capacity, health-related quality of life questionnaires and biomarkers of cardiac function and inflammation. Ethical approval has been granted by St Vincent's Hospital, Sydney (HREC/14/SVH/341). Results of this study will be disseminated through presentation at scientific conferences and in scientific journals. ACTRN12615001041549; pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Left atrial booster function in valvular heart disease.

PubMed

Heidenreich, F P; Shaver, J A; Thompson, M E; Leonard, J J

1970-09-01

This study was designed to assess atrial booster pump action in valvular heart disease and to dissect booster pump from reservoir-conduit functions. In five patients with aortic stenosis and six with mitral stenosis, sequential atrioventricular (A-V) pacing was instituted during the course of diagnostic cardiac catheterization. Continuous recording of valvular gradient allowed estimation of flow for each cardiac cycle by transposition of the Gorlin formula. Left ventricular ejection time and left ventricular stroke work in aortic stenosis or left ventricular mean systolic pressure in mitral stenosis were also determined. Control observations were recorded during sequential A-V pacing with well-timed atrial systole. Cardiac cycles were then produced with no atrial contraction but undisturbed atrial reservoir function by intermittently interrupting the atrial pacing stimulus during sequential A-V pacing. This intervention significantly reduced valvular gradient, flow, left ventricular ejection time, and left ventricular mean systolic pressure or stroke work. Cardiac cycles were then produced with atrial booster action eliminated by instituting synchronous A-V pacing. The resultant simultaneous contraction of the atrium and ventricle not only eliminated effective atrial systole but also placed atrial systole during the normal period of atrial reservoir function. This also significantly reduced all the hemodynamic measurements. However, comparison of the magnitude of change from these two different pacing interventions showed no greater impairment of hemodynamic state when both booster pump action and reservoir function were impaired than when booster pump action alone was impaired. The study confirms the potential benefit of well placed atrial booster pump action in valvular heart disease in man.

Postoperative complications do not influence the pattern of early lung function recovery after lung resection for lung cancer in patients at risk

PubMed Central

2014-01-01

Background The pattern and factors influencing the lung function recovery in the first postoperative days are still not fully elucidated, especially in patients at increased risk. Methods Prospective study on 60 patients at increased risk, who underwent a lung resection for primary lung cancer. Inclusion criteria: complete resection and one or more known risk factors in form of COPD, cardiovascular disorders, advanced age or other comorbidities. Previous myocardial infarction, myocardial revascularization or stenting, cardiac rhythm disorders, arterial hypertension and myocardiopathy determined the increased cardiac risk. The severity of COPD was graded according to GOLD criteria. The trend of the postoperative lung function recovery was assessed by performing spirometry with a portable spirometer. Results Cardiac comorbidity existed in 55%, mild and moderate COPD in 20% and 35% of patients respectively. Measured values of FVC% and FEV1% on postoperative days one, three and seven, showed continuous improvement, with significant difference between the days of measurement, especially between days three and seven. There was no difference in the trend of the lung function recovery between patients with and without postoperative complications. Whilst pO2 was decreasing during the first three days in a roughly parallel fashion in patients with respiratory, surgical complications and in patients without complications, a slight hypercapnia registered on the first postoperative day was gradually abolished in all groups except in patients with cardiac complications. Conclusion Extent of the lung resection and postoperative complications do not significantly influence the trend of the lung function recovery after lung resection for lung cancer. PMID:24884793

Postoperative complications do not influence the pattern of early lung function recovery after lung resection for lung cancer in patients at risk.

PubMed

Ercegovac, Maja; Subotic, Dragan; Zugic, Vladimir; Jakovic, Radoslav; Moskovljevic, Dejan; Bascarevic, Slavisa; Mujovic, Natasa

2014-05-19

The pattern and factors influencing the lung function recovery in the first postoperative days are still not fully elucidated, especially in patients at increased risk. Prospective study on 60 patients at increased risk, who underwent a lung resection for primary lung cancer. complete resection and one or more known risk factors in form of COPD, cardiovascular disorders, advanced age or other comorbidities. Previous myocardial infarction, myocardial revascularization or stenting, cardiac rhythm disorders, arterial hypertension and myocardiopathy determined the increased cardiac risk. The severity of COPD was graded according to GOLD criteria. The trend of the postoperative lung function recovery was assessed by performing spirometry with a portable spirometer. Cardiac comorbidity existed in 55%, mild and moderate COPD in 20% and 35% of patients respectively. Measured values of FVC% and FEV1% on postoperative days one, three and seven, showed continuous improvement, with significant difference between the days of measurement, especially between days three and seven. There was no difference in the trend of the lung function recovery between patients with and without postoperative complications. Whilst pO2 was decreasing during the first three days in a roughly parallel fashion in patients with respiratory, surgical complications and in patients without complications, a slight hypercapnia registered on the first postoperative day was gradually abolished in all groups except in patients with cardiac complications. Extent of the lung resection and postoperative complications do not significantly influence the trend of the lung function recovery after lung resection for lung cancer.

MicroRNA-19a/b-3p protect the heart from hypertension-induced pathological cardiac hypertrophy through PDE5A.

PubMed

Liu, Kun; Hao, Qiongyu; Wei, Jie; Li, Gong-Hao; Wu, Yong; Zhao, Yun-Feng

2018-04-16

PDE5A is a leading factor contributing to cGMP signaling and cardiac hypertrophy. However, microRNA-mediated posttranscriptional regulation of PDE5A has not been reported. The aim of this study is to screen the microRNAs that are able to regulate PDE5A and explore the function of the microRNAs in cardiac hypertrophy and remodeling. Although miR-19a/b-3p (microRNA-19a-3p and microRNA-19b-3p) have been reported to be differentially expressed during cardiac hypertrophy, the direct targets and the functions of this microRNA family for regulation of cardiac hypertrophy have not yet been investigated. The present study identified some direct targets and the underlying functions of miR-19a/b-3p by using bioinformatics tools and gene manipulations within mouse neonatal cardiomyocytes. Transfection of miR-19a/b-3p down-regulated endogenous expressions of PDE5A at both mRNA and protein levels with real-time PCR and western blot. Luciferase reporter assays showed that PDE5A was a direct target of miR-19a/b-3p. In mouse models of cardiac hypertrophy, we found that miR-19a/b-3p was expressed in cardiomyocytes and that its expression was reduced in pressure overload-induced hypertrophic hearts. miR-19a/b-3p transgenic mice prevented the progress of cardiac hypertrophy and cardiac remodeling in response to angiotensin II infusion with echocardiographic assessment and pressure-volume relation analysis. Our study elucidates that PDE5A is a novel direct target of miR-19a/b-3p, and demonstrates that antihypertrophic roles of the miR-19a/b-3p family in Ang II-induced hypertrophy and cardiac remodeling, suggests that endogenous miR-19a/b-3p might have clinical potential to suppress cardiac hypertrophy and heart failure.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

Lung physiology during ECS resuscitation of DCD donors followed by in situ assessment of lung function.

PubMed

Reoma, Junewai L; Rojas, Alvaro; Krause, Eric M; Obeid, Nabeel R; Lafayette, Nathan G; Pohlmann, Joshua R; Padiyar, Niru P; Punch, Jeffery D; Cook, Keith E; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support (ECS) of donors after cardiac death (DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in vivo method to assess if lungs are suitable for transplantation from DCD donors after ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10 min of warm ischemia. Cannulae were placed into the right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90 min with lungs inflated, group 1 (n = 5) or deflated, group 2 (n = 3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-ventricular (bi-VAD) system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1-hr assessment period. The oxygenator was turned off, and ventilation was restarted. Flows, blood gases, PA and left atrial pressures, and compliance were recorded. In both the groups, LA pressure was <15 mm Hg during ECS. During the lung assessment period, PA flows were 1.4-2.2 L/min. PO2 was >300 mm Hg, with normal PCO2. Extracorporeal cardiopulmonary support resuscitation of DCD donors is feasible and allows for assessment of function before procurement. Extracorporeal cardiopulmonary support does not cause pulmonary congestion, and the lungs retain adequate function for transplantation. Compliance correlated with lung function.

LUNG PHYSIOLOGY DURING ECS RESUSCITATION OF DCD DONORS FOLLOWED BY IN-SITU ASSESSMENT OF LUNG FUNCTION

PubMed Central

Reoma, Junewai L.; Rojas, Alvaro; Krause, Eric M.; Obeid, Nabeel R.; Lafayette, Nathan G.; Pohlmann, Joshua R.; Padiyar, Niru P.; Punch, Jeffery D; Cook, Keith E.; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support(ECS) of donors following cardiac death(DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in-vivo method to assess if lungs are suitable for transplantation from DCD donors following ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10min. of warm ischemia. Cannulas were placed into right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90min with lungs inflated, Group 1 (n=5) or deflated Group 2 (n=3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-VAD system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1hr assessment period. The oxygenator was turned off, and ventilation restarted. Flows, blood gases, pulmonary artery and left atrial pressures, and compliance were recorded. In both groups: LA pressure was <15mmHg during ECS. During the lung assessment period, PA flows were 1.4−2.2 liter/min. PO2 was >300mmHg, with normal PCO2. ECS resuscitation of DCD donors is feasible and allows for assessment of function prior to procurement. ECS does not cause pulmonary congestion, and lungs retain adequate function for transplantation. Compliance correlated with lung function. PMID:19506464

Cardiac vagal regulation in infancy predicts executive function and social competence in preschool: Indirect effects through language.

PubMed

Whedon, Margaret; Perry, Nicole B; Calkins, Susan D; Bell, Martha Ann

2018-05-21

Parasympathetic nervous system functioning in infancy may serve a foundational role in the development of cognitive and socioemotional skills (Calkins, 2007). In this study (N = 297), we investigated the potential indirect effects of cardiac vagal regulation in infancy on children's executive functioning and social competence in preschool via expressive and receptive language in toddlerhood. Vagal regulation was assessed at 10 months during two attention conditions (social, nonsocial) via task-related changes in respiratory sinus arrhythmia (RSA). A path analysis revealed that decreased RSA from baseline in the nonsocial condition and increased RSA in the social condition were related to larger vocabularies in toddlerhood. Additionally, children's vocabulary sizes were positively related to their executive function and social competence in preschool. Indirect effects from vagal regulation in both contexts to both 4-year outcomes were significant, suggesting that early advances in language may represent a mechanism through which biological functioning in infancy impacts social and cognitive functioning in childhood. © 2018 Wiley Periodicals, Inc.

Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure.

PubMed

Koyani, Chintan N; Kolesnik, Ewald; Wölkart, Gerald; Shrestha, Niroj; Scheruebel, Susanne; Trummer, Christopher; Zorn-Pauly, Klaus; Hammer, Astrid; Lang, Petra; Reicher, Helga; Maechler, Heinrich; Groschner, Klaus; Mayer, Bernd; Rainer, Peter P; Sourij, Harald; Sattler, Wolfgang; Malle, Ernst; Pelzmann, Brigitte; von Lewinski, Dirk

2017-12-01

Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca 2+ /calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca 2+ -ATPase 2a axis and Na + -Ca 2+ exchanger function in Ca 2+ extrusion. This resulted in reduced sarcoplasmic reticulum Ca 2+ content, diastolic Ca 2+ overload, systolic dysfunction and impaired contractile force. Furthermore, saxagliptin reduced protein kinase C-mediated delayed rectifier K + current that prolonged action potential duration and consequently QTc interval. Importantly, saxagliptin aggravated pre-existing cardiac dysfunction induced by ischemia/reperfusion injury. In conclusion, our novel results provide mechanisms for the off-target deleterious effects of saxagliptin on cardiac function and support the outcome of SAVOR-TIMI 53 trial that linked saxagliptin with the risk of heart failure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model

PubMed Central

Kuai, Qiyuan; Wang, Chunyan; Wang, Yanbing; Li, Weijing; Zhang, Gongqing; Qiao, Zhixin; He, Min; Wang, Xuanlin; Wang, Yu; Jiang, Xingwei; Su, Lihua; He, Yuezhong; Ren, Suping; Yu, Qun

2016-01-01

A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting. PMID:27910887

Cardiac structure and function predicts functional decline in the oldest old.

PubMed

Leibowitz, David; Jacobs, Jeremy M; Lande-Stessman, Irit; Gilon, Dan; Stessman, Jochanan

2018-02-01

Background This study examined the association between cardiac structure and function and the deterioration in activities of daily living (ADLs) in an age-homogenous, community-dwelling population of patients born in 1920-1921 over a five-year follow-up period. Design Longitudinal cohort study. Methods Patients were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920-1921. Patients underwent home echocardiography and were followed up for five years. Dependence was defined as needing assistance with one or more basic ADL. Standard echocardiographic assessment of cardiac structure and function, including systolic and diastolic function, was performed. Reassessment of ADLs was performed at the five-year follow-up. Results A total of 459 patients were included in the study. Of these, 362 (79%) showed a deterioration in at least one ADL at follow-up. Patients with functional deterioration had a significantly higher left ventricular mass index and left atrial volume with a lower ejection fraction. There was no significant difference between the diastolic parameters the groups in examined. When the data were examined categorically, a significantly larger percentage of patients with functional decline had an abnormal left ventricular ejection fraction and left ventricular hypertrophy. The association between left ventricular mass index and functional decline remained significant in all multivariate models. Conclusions In this cohort of the oldest old, an elevated left ventricular mass index, higher left atrial volumes and systolic, but not diastolic dysfunction, were predictive of functional disability.

[Isolated left ventricular non-compaction associated with Ebstein's anomaly. Multimodality non-invasive imaging for the assessment of congenital heart disease].

PubMed

Renilla, Alfredo; Santamarta, Elena; Corros, Cecilia; Martín, María; Barreiro, Manuel; de la Hera, Jesús

2013-01-01

To establish the etiology of heart failure in patients with congenital heart disease can be challenging. Multiple concomitant anomalies that can be missed after an initial diagnosis could be seen in these patients. In patients with congenital heart disease, a more accurate evaluation of cardiac morphology and left ventricular systolic function could be evaluated by recent non-invasive cardiac imaging techniques. We present a rare case where multimodal cardiac imaging was useful to establish the final diagnosis of left ventricular non-compaction associated with Ebstein's anomaly. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

PubMed Central

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-01-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function.

PubMed

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-06-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

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

PubMed

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

2011-01-01

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

Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy

PubMed Central

Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Veeraveedu, Punniyakoti T; Nakamura, Takashi; Arozal, Wawaimuli; Sari, Flori R; Giridharan, Vijayasree V; Soetikno, Vivian; Palaniyandi, Suresh S; Harima, Meilei; Suzuki, Kenji; Nagata, Masaki; Kodama, Makoto; Watanabe, Kenichi

2012-01-01

Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47phox, p67phox, gp91phox and Nox4), fibrosis markers (TGF-β1 and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis. PMID:22268705

Ischemia/reperfusion-induced alterations of enzymatic and signaling functions of the rat cardiac Na+/K+-ATPase: protection by ouabain preconditioning.

PubMed

Belliard, Aude; Gulati, Gaurav K; Duan, Qiming; Alves, Rosana; Brewer, Shannon; Madan, Namrata; Sottejeau, Yoann; Wang, Xiaoliang; Kalisz, Jennifer; Pierre, Sandrine V

2016-10-01

Cardiac glycosides (CG) are traditionally known as positive cardiac inotropes that inhibit Na + /K + -ATPase-dependent ion transport. CG also trigger-specific signaling pathways through the cardiac Na + /K + -ATPase, with beneficial effects in ischemia/reperfusion (I/R) injury (e.g., ouabain preconditioning, known as OPC) and hypertrophy. Our current understanding of hypersensitivity to CG and subsequent toxicity in the ischemic heart is mostly based on specific I/R-induced alterations of the Na + /K + -ATPase enzymatic function and has remained incomplete. The primary goal of this study was to investigate and compare the impact of I/R on Na + /K + -ATPase enzymatic and signaling functions. Second, we assessed the impact of OPC on both functions. Langendorff-perfused rat hearts were exposed to 30 min of ischemia and 30 min of reperfusion. At the inotropic concentration of 50 μmol/L, ouabain increased ERK and Akt phosphorylation in control hearts. In I/R hearts, this concentration did not induced positive inotropy and failed to induce Akt or ERK phosphorylation. The inotropic response to dobutamine as well as insulin signaling persisted, suggesting specific alterations of Na + /K + -ATPase. Indeed, Na + /K + -ATPase protein expression was intact, but the enzyme activity was decreased by 60% and the enzymatic function of the isoform with high affinity for ouabain was abolished following I/R. Strikingly, OPC prevented all I/R-induced alterations of the receptor. Further studies are needed to reveal the respective roles of I/R-induced modulations of Na + /K + -ATPase enzymatic and signaling functions in cardiomyocyte death. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Follow-Up After Cardiac Surgery Should be Extended to at Least 120 Days When Benchmarking Cardiac Surgery Centers.

PubMed

Hansen, Laura S; Sloth, Erik; Hjortdal, Vibeke E; Jakobsen, Carl-Johan

2015-08-01

Short-term (30 days) mortality frequently is used as an outcome measure after cardiac surgery, although it has been proposed that the follow-up period should be extended to 120 days to allow for more accurate benchmarking. The authors aimed to evaluate whether mortality rates 120 days after surgery were comparable to general mortality and to compare causes of death between the cohort and the general population. A multicenter descriptive cohort study using prospectively entered registry data. University hospital. The cohort was obtained from the Western Denmark Heart Registry and matched to the Danish National Hospital Register as well as the Danish Register of Causes of Death. A weighted, age-matched general population consisting of all Danish patients who died within the study period was identified through the central authority on Danish statistics. A total of 11,988 patients (>15 years) who underwent cardiac-surgery at Aarhus, Aalborg and Odense University Hospitals from April 1, 2006 to December 31, 2012 were included. Coronary artery bypass grafting, valve surgery and combinations. Mortality after cardiac surgery matches with mortality in the general population after 140 days. Mortality curves run almost parallel from this point onwards, regardless of The European system for cardiac operative risk evaluation (EuroSCORE) and intervention. The causes of death in the cohort differed statistically significantly from the background population (p<0.0001; one-sample t-test) throughout the first postoperative year. The leading cause of death in the cohort was cardiac (38%); 53% of which was categorized as heart failure. A total of 54% of these patients were assessed preoperatively as having normal or mildly impaired heart function (EuroSCORE). This study supported an extended follow-up period after cardiac surgery when benchmarking cardiac surgery centers. Regardless of preoperative heart function, heart failure was the consistent leading cause of death. Copyright © 2015 Elsevier Inc. All rights reserved.

Kruppel-like factor 15 is required for the cardiac adaptive response to fasting.

PubMed

Sugi, Keiki; Hsieh, Paishiun N; Ilkayeva, Olga; Shelkay, Shamanthika; Moroney, Bridget; Baadh, Palvir; Haynes, Browning; Pophal, Megan; Fan, Liyan; Newgard, Christopher B; Prosdocimo, Domenick A; Jain, Mukesh K

2018-01-01

Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand. Here we show that cardiac KLF15 is required for the normal cardiac response to fasting. Specifically, we find that cardiac function is impaired upon fasting in systemic and cardiac specific Klf15-null mice. Further, cardiac specific Klf15-null mice display a fasting-dependent accumulation of long chain acylcarnitine species along with a decrease in expression of the carnitine translocase Slc25a20. Treatment with a diet high in short chain fatty acids relieves the KLF15-dependent long chain acylcarnitine accumulation and impaired cardiac function in response to fasting. Our observations establish KLF15 as a critical mediator of the cardiac adaptive response to fasting through its regulation of myocardial lipid utilization.

Cardiac Amyloidosis Shows Decreased Diastolic Function as Assessed by Echocardiographic Parameterized Diastolic Filling.

PubMed

Salman, Katrin; Cain, Peter A; Fitzgerald, Benjamin T; Sundqvist, Martin G; Ugander, Martin

2017-07-01

Cardiac amyloidosis is a rare but serious condition with poor survival. One of the early findings by echocardiography is impaired diastolic function, even before the development of cardiac symptoms. Early diagnosis is important, permitting initiation of treatment aimed at improving survival. The parameterized diastolic filling (PDF) formalism entails describing the left ventricular filling pattern during early diastole using the mathematical equation for the motion of a damped harmonic oscillator. We hypothesized that echocardiographic PDF analysis could detect differences in diastolic function between patients with amyloidosis and controls. Pulsed-wave Doppler echocardiography of transmitral flow was measured in 13 patients with amyloid heart disease and 13 age- and gender matched controls. E- waves (2 to 3 per subject) were analyzed using in-house developed software. Nine PDF-derived parameters were obtained in addition to conventional echocardiographic parameters of diastolic function. Compared to controls, cardiac amyloidosis patients had a larger left atrial area (23.7 ± 7.5 cm 2 vs. 18.5 ± 4.8 cm 2 , p = 0.04), greater interventricular septum wall thickness (14.4 ± 2.6 mm vs. 9.3 ± 1.3 mm, p < 0.001), lower e' (0.06 ± 0.02 m/s vs. 0.09 ± 0.02 m/s, p < 0.001) and higher E/e' (18.0 ± 12.9 vs. 7.7 ± 1.3, p = 0.001). The PDF parameter peak resistive force was greater in cardiac amyloidosis patients compared to controls (17.9 ± 5.7 mN vs. 13.1 ± 3.1 mN, p = 0.03), and other PDF parameters did not differ. PDF analysis revealed that patients with cardiac amyloidosis had a greater peak resistive force compared to controls, consistent with a greater degree of diastolic dysfunction. PDF analysis may be useful in characterizing diastolic function in amyloid heart disease. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Cardiac autonomic neuropathy risk estimated by sudomotor function and arterial stiffness in Chinese subjects.

PubMed

Zeng, Q; Dong, S-Y; Wang, M-L; Wang, F; Li, J-M; Zhao, X-L

2016-11-01

The SUDOSCAN test was recently developed to detect diabetic autonomic neuropathy early and screen for cardiac autonomic neuropathy (CAN) through assessment of sudomotor function. The aim of this study was to investigate the relationship of cardiac autonomic dysfunction estimated by the SUDOSCAN test with arterial stiffness. A total of 4019 subjects without diabetes or established cardiovascular disease were tested with SUDOSCAN, central systolic blood pressure (cSBP) and brachial-ankle pulse wave velocity (baPWV). Hands mean electrochemical skin conductance (ESC) measured by SUDOSCAN was 70±17 μS, feet mean ESC was 71±16 μS and the CAN risk score was 21±10%. The levels of cSBP and baPWV increased across quartiles of CAN risk score (P for trend <0.001 for all). In spearman correlation analyses, the CAN risk score was positively correlated with cSBP (r=0.391, P<0.001) and baPWV (r=0.305, P<0.001). In multivariable analyses, the values of cSBP and baPWV increased 0.17 mm Hg (P=0.002) and 2.01 cm per second (P=0.010), respectively, when CAN risk score increased 1%. The results were unchanged when stratified by glucose tolerance status. In conclusion, cardiac autonomic dysfunction estimated by sudomotor function was correlated with arterial stiffness independent of conventional factors and glucose tolerance status.

TRPA1 mediates changes in heart rate variability and cardiac ...

EPA Pesticide Factsheets

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described; however, the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3ppm acrolein, 0.3ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to ac

Cardiac integrins the ties that bind.

PubMed

Simpson, D G; Reaves, T A; Shih, D T; Burgess, W; Borg, T K; Terracio, L

1998-01-01

An elaborate series of morphogenetic events must be precisely coordinated during development to promote the formation of the elaborate three-dimensional structure of the normal heart. In this study we focus on discussing how interconnections between the cardiac myocyte and its surrounding environment regulate cardiac form and function. In vitro experiments from our laboratories provide direct evidence that cardiac cell shape is regulated by a dynamic interaction between constituents of the extracellular matrix (ECM) and by specific members of the integrin family of matrix receptors. Our data indicates that phenotypic information is stored in the tertiary structure and chemical identity of the ECM. This information appears to be actively communicated and transduced by the α1β1 integrin molecule into an intracellular signal that regulates cardiac cell shape and myofibrillar organization. In this study we have assessed the phenotypic consequences of suppressing the expression and accumulation of the α1 integrin molecule in aligned cultures of cardiac myocytes. In related experiments we have examined how the overexpression of α2 and α5 integrin, integrins normally not present or present at very low copy number on the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism. We also consider how biochemical signals and the mechanical signals mediated by the integrins may converge on common intracellular signaling pathways in the heart. Experiments with the whole embryo culture system indicate that angiotensin II, a peptide that carries information concerning cardiac load, plays a role in controling cardiac looping and the proliferation of myofibrils during development.

Functional Strain-Line Pattern in the Human Left Ventricle

NASA Astrophysics Data System (ADS)

Pedrizzetti, Gianni; Kraigher-Krainer, Elisabeth; De Luca, Alessio; Caracciolo, Giuseppe; Mangual, Jan O.; Shah, Amil; Toncelli, Loira; Domenichini, Federico; Tonti, Giovanni; Galanti, Giorgio; Sengupta, Partho P.; Narula, Jagat; Solomon, Scott

2012-07-01

Analysis of deformations in terms of principal directions appears well suited for biological tissues that present an underlying anatomical structure of fiber arrangement. We applied this concept here to study deformation of the beating heart in vivo analyzing 30 subjects that underwent accurate three-dimensional echocardiographic recording of the left ventricle. Results show that strain develops predominantly along the principal direction with a much smaller transversal strain, indicating an underlying anisotropic, one-dimensional contractile activity. The strain-line pattern closely resembles the helical anatomical structure of the heart muscle. These findings demonstrate that cardiac contraction occurs along spatially variable paths and suggest a potential clinical significance of the principal strain concept for the assessment of mechanical cardiac function. The same concept can help in characterizing the relation between functional and anatomical properties of biological tissues, as well as fiber-reinforced engineered materials.

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

PubMed

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

2016-04-28

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

Issues in solid-organ transplantation in children: translational research from bench to bedside

PubMed Central

Lipshultz, Steven E.; Chandar, Jayanthi J.; Rusconi, Paolo G.; Fornoni, Alessia; Abitbol, Carolyn L.; Burke III, George W.; Zilleruelo, Gaston E.; Pham, Si M.; Perez, Elena E.; Karnik, Ruchika; Hunter, Juanita A.; Dauphin, Danielle D.; Wilkinson, James D.

2014-01-01

In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children. PMID:24860861

[Cardiac cachexia].

PubMed

Miján, Alberto; Martín, Elvira; de Mateo, Beatriz

2006-05-01

Chronic heart failure (CHF), especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular) mass and adipose and bone tissue osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

Influence of antipsychotic agents on heart rate variability in male WKY rats: implications for cardiovascular safety.

PubMed

Wang, Ying-Chieh; Chen, Chun-Yu; Kuo, Terry B J; Lai, Ching-Jung; Yang, Cheryl C H

2012-06-01

Sudden cardiac death is higher among schizophrenic patients and is associated with parasympathetic hypoactivity. Antipsychotic agents are highly suspected to be a precipitating factor. Thus, we aimed to test if the antipsychotics haloperidol, risperidone and clozapine affect cardiac autonomic function, excluding the confounding effect of altered sleep structure by the drugs. In this study, haloperidol, risperidone and clozapine were given separately by intraperitoneal injection to male Wistar-Kyoto rats for 5 days. Electroencephalogram (EEG), electromyogram (EMG) and electrocardiographic signals were recorded at baseline and 5 days after drug treatments. Sleep scoring was based on EEG and EMG signals. Cardiac autonomic function was assessed using heart rate variability analysis. Clozapine increased heart rate and suppressed cardiac sympathetic and parasympathetic activity. Cardiac acceleration was more severe during sleep. Haloperidol tended to decrease heart rate while risperidone mildly increased heart rate; however, their effects were less obvious than those of clozapine. There was a significant drug-by-stage interaction on several heart rate variability measures. Taking this evidence as a whole, we conclude that haloperidol has a better level of cardiovascular safety than either risperidone or clozapine. Application of this approach to other psychotropic agents in the future will be a useful and helpful way to evaluate the cardiovascular safety of the various psychotropic medications that are in clinical use. Copyright © 2012 S. Karger AG, Basel.

Cardiac parasympathetic regulation in obese women with binge eating disorder.

PubMed

Friederich, H-C; Schild, S; Schellberg, D; Quenter, A; Bode, C; Herzog, W; Zipfel, S

2006-03-01

Obese individuals with a binge eating disorder (BED) differ from obese non-binge eaters (NBED) with respect to (a) eating behaviour, (b) psychiatric comorbidity and (c) level of psychosocial distress. The aim of the study was to explore whether these three factors have an influence on cardiac parasympathetic function, that is independent of obesity: as alterations in cardiac parasympathetic function may have a role in the higher cardiovascular mortality that is present in obese individuals. In total, 38 obese women (BMI>30 kg/m(2)), with a BED and 34 age and BMI matched healthy controls (NBED) completed a laboratory stress protocol that incorporated a baseline resting period, Head-up Tilt Testing (HUT) and two challenging mental tasks. Heart rate and blood pressure were measured continuously during the protocol. Parasympathetic cardiac regulation was assessed as the high frequency component of heart rate variability (HRV-HF). Mental challenge led to an augmented reduction of HRV-HF in obese binge eaters, which was linked to the binge eating frequency and hunger perception, but not to psychiatric comorbidity. During baseline conditions and HUT, no significant differences in parasympathetic measures were observed between the two subject groups. Subjects with a BED showed greater reduction in parasympathetic cardiac control (HRV-HF) during mental stress, suggesting higher stress vulnerability in women with a BED. Longitudinal investigations are necessary to evaluate whether this is associated with an increased cardiovascular mortality.

A Comparison of Electrospun Polymers Reveals Poly(3-Hydroxybutyrate) Fiber as a Superior Scaffold for Cardiac Repair

PubMed Central

Castellano, Delia; Blanes, María; Marco, Bruno; Cerrada, Inmaculada; Ruiz-Saurí, Amparo; Pelacho, Beatriz; Araña, Miriam; Montero, Jose A.; Cambra, Vicente; Prosper, Felipe

2014-01-01

The development of biomaterials for myocardial tissue engineering requires a careful assessment of their performance with regards to functionality and biocompatibility, including the immune response. Poly(3-hydroxybutyrate) (PHB), poly(e-caprolactone) (PCL), silk, poly-lactic acid (PLA), and polyamide (PA) scaffolds were generated by electrospinning, and cell compatibility in vitro, and immune response and cardiac function in vitro and in vivo were compared with a noncrosslinked collagen membrane (Col) control material. Results showed that cell adhesion and growth of mesenchymal stem cells, cardiomyocytes, and cardiac fibroblasts in vitro was dependent on the polymer substrate, with PHB and PCL polymers permitting the greatest adhesion/growth of cells. Additionally, polymer substrates triggered unique expression profiles of anti- and pro-inflammatory cytokines in human peripheral blood mononuclear cells. Implantation of PCL, silk, PLA, and PA patches on the epicardial surface of healthy rats induced a classical foreign body reaction pattern, with encapsulation of polymer fibers and induction of the nonspecific immune response, whereas Col and PHB patches were progressively degraded. When implanted on infarcted rat heart, Col, PCL, and PHB reduced negative remodeling, but only PHB induced significant angiogenesis. Importantly, Col and PHB modified the inflammatory response to an M2 macrophage phenotype in cardiac tissue, indicating a more beneficial reparative process and remodeling. Collectively, these results identify PHB as a superior substrate for cardiac repair. PMID:24564648

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

PubMed

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

2016-12-01

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

[Assessment of professional practices in treating cardiac arrest].

PubMed

Mazon, Clara; Kerrou, Yamina

2017-12-01

An assessment of professional practices was carried out in 2013-2014 with the aim of improving the treatment of cardiac arrest in hospitals. Two methods were used: an assessment by questionnaire to evaluate theoretical knowledge and a practical assessment of external cardiac massage. The results highlight the need for greater knowledge. The use of cardiac massage must be included in continuing professional development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The relationship between erythrocyte membrane fatty acid levels and cardiac autonomic function in obese children.

PubMed

Mustafa, Gulgun; Kursat, Fidanci Muzaffer; Ahmet, Tas; Alparslan, Genc Fatih; Omer, Gunes; Sertoglu, Erdem; Erkan, Sarı; Ediz, Yesilkaya; Turker, Turker; Ayhan, Kılıc

Childhood obesity is a worldwide health concern. Studies have shown autonomic dysfunction in obese children. The exact mechanism of this dysfunction is still unknown. The aim of this study was to assess the relationship between erythrocyte membrane fatty acid (EMFA) levels and cardiac autonomic function in obese children using heart rate variability (HRV). A total of 48 obese and 32 healthy children were included in this case-control study. Anthropometric and biochemical data, HRV indices, and EMFA levels in both groups were compared statistically. HRV parameters including standard deviation of normal-to-normal R-R intervals (NN), root mean square of successive differences, the number of pairs of successive NNs that differ by >50 ms (NN50), the proportion of NN50 divided by the total number of NNs, high-frequency power, and low-frequency power were lower in obese children compared to controls, implying parasympathetic impairment. Eicosapentaenoic acid and docosahexaenoic acid levels were lower in the obese group (p<0.001 and p=0.012, respectively). In correlation analysis, in the obese group, body mass index standard deviation and linoleic acid, arachidonic acid, triglycerides, and high-density lipoprotein levels showed a linear correlation with one or more HRV parameter, and age, eicosapentaenoic acid, and systolic and diastolic blood pressure correlated with mean heart rate. In linear regression analysis, age, dihomo-gamma-linolenic acid, linoleic acid, arachidonic acid, body mass index standard deviation, systolic blood pressure, triglycerides, low-density lipoprotein and high-density lipoprotein were related to HRV parameters, implying an effect on cardiac autonomic function. There is impairment of cardiac autonomic function in obese children. It appears that levels of EMFAs such as linoleic acid, arachidonic acid and dihomo-gamma-linolenic acid play a role in the regulation of cardiac autonomic function in obese children. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

The adenosine A2A receptor — Myocardial protectant and coronary target in endotoxemia

PubMed Central

Reichelt, Melissa E.; Ashton, Kevin J.; Tan, Xing Lin; Mustafa, S. Jamal; Ledent, Catherine; Delbridge, Lea M.D.; Hofmann, Polly A.; Headrick, John P.; Morrison, R. Ray

2013-01-01

Background Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation. Methods We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO). Results Cardiac injury was evident in LPS-treated WTs, with ∼7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by 3-fold without additional demise of contraction function. Importantly, A2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A2AARs. Effects of A2AAR KO were independent of major shifts in circulating C-reactive protein (CRP) and haptoglobin. Cytokine responses were largely insensitive to A2AAR deletion; substantial LPS-induced elevations (up to 100-fold) in IFN-γ and IL-10 were unaltered in A2AAR KO mice, as were levels of IL-4 and TNF-α. However, late elevations in IL-2 and IL-5 were differentially modulated by A2AAR KO (IL-2 reduced, IL-5 increased). Data demonstrate that in the context of LPS-triggered cardiac and coronary injury, A2AAR activity protects myocardial viability without modifying contractile dysfunction, and selectively modulates cytokine (IL-2, IL-5) release. A2AARs also appear to be targeted by LPS in the coronary vasculature. Conclusions These experimental data suggest that preservation of A2AAR functionality might provide therapeutic benefit in human sepsis. PMID:22192288

Cardiovascular risk assessment in type 2 diabetes mellitus: comparison of the World Health Organization/International Society of Hypertension risk prediction charts versus UK Prospective Diabetes Study risk engine.

PubMed

Herath, Herath M Meththananda; Weerarathna, Thilak Priyantha; Umesha, Dilini

2015-01-01

Patients with type 2 diabetes mellitus (T2DM) are at higher risk of developing cardiovascular diseases, and assessment of their cardiac risk is important for preventive strategies. The Ministry of Health of Sri Lanka has recommended World Health Organization/International Society of Hypertension (WHO/ISH) charts for cardiac risk assessment in individuals with T2DM. However, the most suitable cardiac risk assessment tool for Sri Lankans with T2DM has not been studied. This study was designed to evaluate the performance of two cardiac risk assessments tools; WHO/ISH charts and UK Prospective Diabetes Study (UKPDS) risk engine. Cardiac risk assessments were done in 2,432 patients with T2DM attending a diabetes clinic in Southern Sri Lanka using the two risk assessment tools. Validity of two assessment tools was further assessed by their ability to recognize individuals with raised low-density lipoprotein (LDL) and raised diastolic blood pressure in a cohort of newly diagnosed T2DM patients (n=332). WHO/ISH charts identified 78.4% of subjects as low cardiac risk whereas the UKPDS risk engine categorized 52.3% as low cardiac risk (P<0.001). In the risk categories of 10%-<20%, the UKPDS risk engine identified higher proportions of patients (28%) compared to WHO/ISH charts (7%). Approximately 6% of subjects were classified as low cardiac risk (<10%) by WHO/ISH when UKPDS recognized them as cardiac risk of >20%. Agreement between the two tools was poor (κ value =0.144, P<0.01). Approximately 82% of individuals categorized as low cardiac risk by WHO/ISH had higher LDL cholesterol than the therapeutic target of 100 mg/dL. There is a significant discrepancy between the two assessment tools with WHO/ISH risk chart recognizing higher proportions of patients having low cardiac risk than the UKPDS risk engine. Risk assessment by both assessment tools demonstrated poor sensitivity in identifying those with treatable levels of LDL cholesterol and diastolic blood pressure.

Effects of cardiac energy efficiency in diastolic heart failure: assessment with positron emission tomography with 11C-acetate.

PubMed

Hasegawa, Shinji; Yamamoto, Kazuhiro; Sakata, Yasushi; Takeda, Yasuharu; Kajimoto, Katsufumi; Kanai, Yasukazu; Hori, Masatsugu; Hatazawa, Jun

2008-06-01

Diastolic heart failure (DHF) has become a high social burden, and its major underlying cardiovascular disease is hypertensive heart disease. However, the pathogenesis of DHF remains to be clarified. This study aimed to assess the effects of cardiac energy efficiency in DHF patients. (11)C-Acetate positron emission tomography and echocardiography were conducted in 11 DHF Japanese patients and 10 normal volunteers. The myocardial clearance rate of radiolabeled (11)C-acetate was measured to calculate the work metabolic index (WMI), an index of cardiac efficiency. The ratio of peak mitral E wave velocity to peak early diastolic septal myocardial velocity (E/e') was calculated to assess left ventricular (LV) filling pressure. The LV mass index was greater and the mean age was higher in the DHF patients than in the normal volunteers. There was no difference in WMI between the two groups. However, WMI varied widely among the DHF patients and was inversely correlated with E/e' (r=-0.699, p=0.017). In contrast, there was no correlation in the normal volunteers. In conclusion, the inefficiency of energy utilization is not a primary cause of diastolic dysfunction or DHF, and cardiac efficiency may not affect diastolic function in normal hearts. However, the energy-wasting state may induce the elevation of LV filling pressure in DHF patients, which was considered to principally result from the progressive diastolic dysfunction.

Novel Wearable Seismocardiography and Machine Learning Algorithms Can Assess Clinical Status of Heart Failure Patients.

PubMed

Inan, Omer T; Baran Pouyan, Maziyar; Javaid, Abdul Q; Dowling, Sean; Etemadi, Mozziyar; Dorier, Alexis; Heller, J Alex; Bicen, A Ozan; Roy, Shuvo; De Marco, Teresa; Klein, Liviu

2018-01-01

Remote monitoring of patients with heart failure (HF) using wearable devices can allow patient-specific adjustments to treatments and thereby potentially reduce hospitalizations. We aimed to assess HF state using wearable measurements of electrical and mechanical aspects of cardiac function in the context of exercise. Patients with compensated (outpatient) and decompensated (hospitalized) HF were fitted with a wearable ECG and seismocardiogram sensing patch. Patients stood at rest for an initial recording, performed a 6-minute walk test, and then stood at rest for 5 minutes of recovery. The protocol was performed at the time of outpatient visit or at 2 time points (admission and discharge) during an HF hospitalization. To assess patient state, we devised a method based on comparing the similarity of the structure of seismocardiogram signals after exercise compared with rest using graph mining (graph similarity score). We found that graph similarity score can assess HF patient state and correlates to clinical improvement in 45 patients (13 decompensated, 32 compensated). A significant difference was found between the groups in the graph similarity score metric (44.4±4.9 [decompensated HF] versus 35.2±10.5 [compensated HF]; P <0.001). In the 6 decompensated patients with longitudinal data, we found a significant change in graph similarity score from admission (decompensated) to discharge (compensated; 44±4.1 [admitted] versus 35±3.9 [discharged]; P <0.05). Wearable technologies recording cardiac function and machine learning algorithms can assess compensated and decompensated HF states by analyzing cardiac response to submaximal exercise. These techniques can be tested in the future to track the clinical status of outpatients with HF and their response to pharmacological interventions. © 2018 American Heart Association, Inc.

Ultrasonographic Measures of Volume Responsiveness

DTIC Science & Technology

2017-02-01

variation, focused rapid echocardiographic evaluation , FREE, point-of-care ultrasound, POCUS, cardiac ultrasound 16. SECURITY CLASSIFICATION OF: 17...in small populations of medical patients on standard ventilator setting. There are very few studies directly comparing measures, or evaluating the...function are assessed as part of the FREE. Several predicative measures described below were assessed in the pre-TTE evaluation (Table 1). 4.2.1

Cardiac microRNA-133 is down-regulated in thyroid hormone-mediated cardiac hypertrophy partially via Type 1 Angiotensin II receptor.

PubMed

Diniz, Gabriela Placoná; Lino, Caroline Antunes; Guedes, Elaine Castilho; Moreira, Luana do Nascimento; Barreto-Chaves, Maria Luiza Morais

2015-09-01

Elevated thyroid hormone (TH) levels induce cardiac hypertrophy partially via type 1 Angiotensin II receptor (AT1R). MicroRNAs (miRNAs) are key regulators of cardiac homeostasis, and miR-133 has been shown to be involved in cardiac hypertrophy. However, the potential role of miR-133 in cardiac growth induced by TH is unknown. Thus, we aimed to investigate the miR-133 expression, as well as its potential role in cardiac hypertrophy in response to TH. Wistar rats were subjected to hyperthyroidism combined or not with the AT1R blocker. T3 serum levels were assessed to confirm the hyperthyroid status. TH induced cardiac hypertrophy, as evidenced by higher cardiac weight/tibia length ratio and α-actin mRNA levels, which was prevented by AT1R blocker. miR-133 expression was decreased in TH-induced cardiac hypertrophy in part through the AT1R. Additionally, the cardiac mRNA levels of miR-133 targets, SERCA2a and calcineurin were increased in hyperthyroidism partially via AT1R, as evaluated by real-time RT-PCR. Interestingly, miR-133 levels were unchanged in T3-induced cardiomyocyte hypertrophy in vitro. However, a gain-of-function study revealed that miR-133 mimic blunted the T3-induced cardiomyocyte hypertrophy in vitro. Together, our data indicate that miR-133 expression is reduced in TH-induced cardiac hypertrophy partially by the AT1R and that miR-133 mimic prevents the cardiomyocyte hypertrophy in response to T3 in vitro. These findings provide new insights regarding the mechanisms involved in the cardiac growth mediated by TH, suggesting that miR-133 plays a key role in TH-induced cardiomyocyte hypertrophy.

Capnography in the Emergency Department: A Review of Uses, Waveforms, and Limitations.

PubMed

Long, Brit; Koyfman, Alex; Vivirito, Michael A

2017-12-01

Capnography has many uses in the emergency department (ED) and critical care setting, most commonly cardiac arrest and procedural sedation. This review evaluates several indications concerning capnography beyond cardiac arrest and procedural sedation in the ED, as well as limitations and specific waveforms. Capnography includes the noninvasive measurement of CO 2 , providing information on ventilation, perfusion, and metabolism in intubated and spontaneously breathing patients. Since the 1990s, capnography has been utilized extensively for cardiac arrest and procedural sedation. Qualitative capnography includes a colorimetric device, changing color on the amount of CO 2 present. Quantitative capnography provides a numeric value (end-tidal CO 2 ), and capnography most commonly includes a waveform as a function of time. Conditions in which capnography is informative include cardiac arrest, procedural sedation, mechanically ventilated patients, and patients with metabolic acidemia. Patients with seizure, trauma, and respiratory conditions, such as pulmonary embolism and obstructive airway disease, can benefit from capnography, but further study is needed. Limitations include use of capnography in conditions with mixed pathophysiology, patients with low tidal volumes, and equipment malfunction. Capnography should be used in conjunction with clinical assessment. Capnography demonstrates benefit in cardiac arrest, procedural sedation, mechanically ventilated patients, and patients with metabolic acidemia. Further study is required in patients with seizure, trauma, and respiratory conditions. It should only be used in conjunction with other patient factors and clinical assessment. Published by Elsevier Inc.

Continuous cardiac troponin I release in Fabry disease.

PubMed

Feustel, Andreas; Hahn, Andreas; Schneider, Christian; Sieweke, Nicole; Franzen, Wolfgang; Gündüz, Dursun; Rolfs, Arndt; Tanislav, Christian

2014-01-01

Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD. cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females) regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI). Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05-0.71 ng/ml, normal: <0.01). cMRI disclosed late gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3) in cardiomyocytes. Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD.

The Dark Side of the Moon: The Right Ventricle

PubMed Central

Foschi, Massimiliano; Di Mauro, Michele; Tancredi, Fabrizio; Capparuccia, Carlo; Petroni, Renata; Leonzio, Luigi; Romano, Silvio; Gallina, Sabina; Penco, Maria; Cibelli, Mario; Calafiore, Antonio

2017-01-01

The aim of this review article is to summarize current knowledge of the pathophysiology underlying right ventricular failure (RVF), focusing, in particular, on right ventricular assessment and prognosis. The right ventricle (RV) can tolerate volume overload well, but is not able to sustain pressure overload. Right ventricular hypertrophy (RVH), as a response to increased afterload, can be adaptive or maladaptive. The easiest and most common way to assess the RV is by two-dimensional (2D) trans-thoracic echocardiography measuring surrogate indexes, such as tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and tissue Doppler velocity of the lateral aspect of the tricuspid valvular plane. However, both volumes and function are better estimated by 3D echocardiography and cardiac magnetic resonance (CMR). The prognostic role of the RV in heart failure (HF), pulmonary hypertension (PH), acute myocardial infarction (AMI), and cardiac surgery has been overlooked for many years. However, several recent studies have placed much greater importance on the RV in prognostic assessments. In conclusion, RV dimensions and function should be routinely assessed in cardiovascular disease, as RVF has a significant impact on disease prognosis. In the presence of RVF, different therapeutic approaches, either pharmacological or surgical, may be beneficial. PMID:29367547

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

PubMed

Lu, Yi; Zhao, Ming; Liu, Jin-Jun; He, Xi; Yu, Xiao-Jiang; Liu, Long-Zhu; Sun, Lei; Chen, Li-Na; Zang, Wei-Jin

2017-09-01

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Automated classification of LV regional wall motion based on spatio-temporal profiles from cardiac cine magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Mantilla, Juan; Garreau, Mireille; Bellanger, Jean-Jacques; Paredes, José Luis

2013-11-01

Assessment of the cardiac Left Ventricle (LV) wall motion is generally based on visual inspection or quantitative analysis of 2D+t sequences acquired in short-axis cardiac cine-Magnetic Resonance Imaging (MRI). Most often, cardiac dynamic is globally analized from two particular phases of the cardiac cycle. In this paper, we propose an automated method to classify regional wall motion in LV function based on spatio-temporal pro les and Support Vector Machines (SVM). This approach allows to obtain a binary classi cation between normal and abnormal motion, without the need of pre-processing and by exploiting all the images of the cardiac cycle. In each short- axis MRI slice level (basal, median, and apical), the spatio-temporal pro les are extracted from the selection of a subset of diametrical lines crossing opposites LV segments. Initialized at end-diastole phase, the pro les are concatenated with their corresponding projections into the succesive temporal phases of the cardiac cycle. These pro les are associated to di erent types of information that derive from the image (gray levels), Fourier, Wavelet or Curvelet domains. The approach has been tested on a set of 14 abnormal and 6 healthy patients by using a leave-one-out cross validation and two kernel functions for SVM classi er. The best classi cation performance is yielded by using four-level db4 wavelet transform and SVM with a linear kernel. At each slice level the results provided a classi cation rate of 87.14% in apical level, 95.48% in median level and 93.65% in basal level.

Sodium Butyrate Protects -Against High Fat Diet-Induced Cardiac Dysfunction and Metabolic Disorders in Type II Diabetic Mice.

PubMed

Zhang, Ling; Du, Jianfeng; Yano, Naohiro; Wang, Hao; Zhao, Yu Tina; Dubielecka, Patrycja M; Zhuang, Shougang; Chin, Y Eugene; Qin, Gangjian; Zhao, Ting C

2017-08-01

Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in Type II diabetes and obesity remains unknown. Here, we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively. Glucose intolerance, metabolic parameters, cardiac function, and remodeling were assessed. Histological analysis and cellular signaling were examined at 24 weeks following euthanization of mice. HFD-fed mice demonstrated myocardial dysfunction and profound interstitial fibrosis, which were attenuated by HDAC inhibition. HFD-induced metabolic syndrome features insulin resistance, obesity, hyperinsulinemia, hyperglycemia, lipid accumulations, and cardiac hypertrophy, these effects were prevented by HDAC inhibition. Furthermore, HDAC inhibition attenuated myocyte apoptosis, reduced production of reactive oxygen species, and increased angiogenesis in the HFD-fed myocardium. Notably, HFD induced decreases in MKK3, p38, p38 regulated/activated protein kinase (PRAK), and Akt-1, but not p44/42 phosphorylation, which were prevented by HDAC inhibition. These results suggest that HDAC inhibition plays a critical role to preserve cardiac performance and mitigate metabolic disorders in obesity and diabetes, which is associated with MKK3/p38/PRAK pathway. The study holds promise in developing a new therapeutic strategy in the treatment of Type II diabetic-induced heart failure and metabolic disorders. J. Cell. Biochem. 118: 2395-2408, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Risk stratification for therapeutic management and prognosis.

PubMed

Coelho-Filho, Otavio R; Nallamshetty, Leelakrishna; Kwong, Raymond Y

2009-07-01

In coronary artery disease (CAD), cardiac magnetic resonance (CMR) imaging can integrate several types of pulse-sequence examinations (eg, myocardial perfusion, cine wall motion, T2-weighted imaging for myocardial edema, late gadolinium enhancement, and CMR angiography) that can provide anatomic, functional, and physiologic information about the heart in a single imaging session. Because of this ability to interrogate myocardial physiology using different pulse sequence techniques within a single CMR session, this technique has been recognized increasingly in many centers as the test of choice for assessing patients who present with cardiomyopathy of undetermined cause. This article first reviews the current evidence supporting the prognosticating role of CMR in assessing CAD and then discusses CMR applications and prognostication in many non-coronary cardiac conditions.

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

NASA Astrophysics Data System (ADS)

Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 ° head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 ° upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alterating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

1998-01-01

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

The effect of garden designs on mood and heart output in older adults residing in an assisted living facility.

PubMed

Goto, Seiko; Park, Bum-Jin; Tsunetsugu, Yuko; Herrup, Karl; Miyazaki, Yoshifumi

2013-01-01

The objective of this study is to trace short-term changes in mood and heart function in elderly individuals in response to exposure to different landscaped spaces. Nineteen elderly but cognitively intact residents of an assisted living facility participated in the study. They were exposed to three landscaped spaces: a Japanese style garden, an herb garden, and a simple landscaped area planted with a single tree. To assess the effect of different landscaped spaces on older adults, individuals were monitored for mood and cardiac function in response to short exposures to spaces. Mood state was assessed using Profile of Mood States (POMS) before and after viewing the spaces. Cardiac output was assessed using a portable electrocardiograph monitor before and during the viewing. We found that the structured gardens evoked greater responses in all outcome measures. Scores on the POMS improved after observation of the two organized gardens compared to responses to the simple landscaped space with a single tree. During the observation period, heart rate was significantly lower in the Japanese garden than in the other environments, and sympathetic function was significantly lower as well. We conclude that exposure to organized gardens can affect both the mood and cardiac physiology of elderly individuals. Our data further suggest that these effects can differ depending on the types of landscape to which an individual is exposed. Elderly, Japanese garden, herb garden, heart rate, mood, healing environmentPreferred Citation: Goto, S., Park, B-J., Tsunetsugu, Y., Herrup, K., & Miyazaki, Y. (2013). The effect of garden designs on mood and heart output in older adults residing in an assisted living facility. Health Environments Research & Design Journal 6(2), pp 27-42.

Nanotized PPARα Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3β-Mediated Mitochondrial Death Pathway.

PubMed

Rana, Santanu; Datta, Ritwik; Chaudhuri, Ratul Datta; Chatterjee, Emeli; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

2018-05-09

Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (PPARα). Thereby, we hypothesized that a cardiac-specific induction of PPARα might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPARα augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy. Nanotized PPARα overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of PPARα ameliorated pathological hypertrophy and improved cardiac function. Augmented PPARα in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPARα with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3β (GSK3β), which upregulated inactive phospho-GSK3β (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in PPARα-overexpressed hypertrophy groups restored mitochondrial structure and function both in vitro and in vivo. Cardiomyocyte-targeted overexpression of a protein of interest (PPARα) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted PPARα-overexpressed myocardium. PPARα-overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of PPARα during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac function, thereby, opening up a potential avenue for cardiac tissue engineering during hypertrophic cardiac pathophysiology.

Cardio-hepatic risk assessment by CMR imaging in liver transplant candidates.

PubMed

Reddy, Sahadev T; Thai, Ngoc L; Oliva, Jose; Tom, Kusum B; Dishart, Michael K; Doyle, Mark; Yamrozik, June A; Williams, Ronald B; Shah, Moneal; Wani, Adil; Singh, Anil; Maheswary, Rishi; Biederman, Robert W W

2018-03-02

The preoperative workup of orthotopic liver transplantation (OLT) patients is practically complex given the need for multiple imaging modalities. We recently demonstrated in our proof-of-concept study the value of a one-stop-shop approach using cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of hepatocellular carcinoma (HCC) as well as cardiovascular risk assessment is critically important in these patients. We hypothesized that coronary risk assessment and HCC detectability is acceptable using the one-stop-shop CMR approach. In this observational study, patients underwent CMRI evaluation including cardiac function, stress CMR, thoracoabdominal MRA, and abdominal MRI on a standard MRI scanner in one examination. Over 8 years, 252 OLT candidates underwent evaluation in the cardiac MRI suit. The completion rates for each segment of the CMR examination were 99% for function, 95% completed stress CMR, 93% completed LGE for viability, 85% for liver MRI, and 87% for MRA. A negative CMR stress examination had 100% CAD event-free survival at 12 months. A total of 63 (29%) patients proceeded to OLT. Explant pathology confirmed detection/exclusion of HCC. This study further defines the population suitable for the one-stop-shop CMR concept for preop evaluation of OLT candidates providing a road map for integrated testing in this complex patient population for evaluation of cardiac risk and detection of HCC lesions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged Mice with Impaired Nrf2 Signaling

PubMed Central

Shanmugam, Gobinath; Narasimhan, Madhusudhanan; Conley, Robbie L.; Sairam, Thiagarajan; Kumar, Ashutosh; Mason, Ronald P.; Sankaran, Ramalingam; Hoidal, John R.; Rajasekaran, Namakkal S.

2017-01-01

Nuclear factor erythroid 2 related factor 2 (Nrf2) signaling maintains the redox homeostasis and its activation is shown to suppress cardiac maladaptation. Earlier we reported that acute endurance exercise (2 days) evoked antioxidant cytoprotection in young WT animals but not in aged WT animals. However, the effect of repeated endurance exercise during biologic aging (WT) characterized by an inherent deterioration in Nrf2 signaling and pathological aging (pronounced oxidative susceptibility—Nrf2 absence) in the myocardium remains elusive. Thus, the purpose of our study was to determine the effect of chronic endurance exercise-induced cardiac adaptation in aged mice with and without Nrf2. Age-matched WT and Nrf2-null mice (Nrf2−/−) (>22 months) were subjected to 6 weeks chronic endurance exercise (25 meter/min, 12% grade). The myocardial redox status was assessed by expression of antioxidant defense genes and proteins along with immunochemical detection of DMPO-radical adduct, GSH-NEM, and total ubiquitination. Cardiac functions were assessed by echocardiography and electrocardiogram. At sedentary state, loss of Nrf2 resulted in significant downregulation of antioxidant gene expression (Nqo1, Ho1, Gclm, Cat, and Gst-α) with decreased GSH-NEM immuno-fluorescence signals. While Nrf2−/− mice subjected to CEE showed an either similar or more pronounced reduction in the transcript levels of Gclc, Nqo1, Gsr, and Gst-α in relation to WT littermates. In addition, the hearts of Nrf2−/− on CEE showed a substantial reduction in specific antioxidant proteins, G6PD and CAT along with decreased GSH, a pronounced increase in DMPO-adduct and the total ubiquitination levels. Further, CEE resulted in a significant upregulation of hypertrophy genes (Anf, Bnf, and β-Mhc) (p < 0.05) in the Nrf2−/− hearts in relation to WT mice. Moreover, the aged Nrf2−/− mice exhibited a higher degree of cardiac remodeling in association with a significant decrease in fractional shortening, pronounced ST segment, and J wave elevation upon CEE compared to age-matched WT littermates. In conclusion, our findings indicate that while the aged WT and Nrf2 knockout animals both exhibit hypertrophy after CEE, the older Nrf2 knockouts showed ventricular remodeling coupled with profound cardiac functional abnormalities and diastolic dysfunction. PMID:28515695

2D/3D fetal cardiac dataset segmentation using a deformable model.

PubMed

Dindoyal, Irving; Lambrou, Tryphon; Deng, Jing; Todd-Pokropek, Andrew

2011-07-01

To segment the fetal heart in order to facilitate the 3D assessment of the cardiac function and structure. Ultrasound acquisition typically results in drop-out artifacts of the chamber walls. The authors outline a level set deformable model to automatically delineate the small fetal cardiac chambers. The level set is penalized from growing into an adjacent cardiac compartment using a novel collision detection term. The region based model allows simultaneous segmentation of all four cardiac chambers from a user defined seed point placed in each chamber. The segmented boundaries are automatically penalized from intersecting at walls with signal dropout. Root mean square errors of the perpendicular distances between the algorithm's delineation and manual tracings are within 2 mm which is less than 10% of the length of a typical fetal heart. The ejection fractions were determined from the 3D datasets. We validate the algorithm using a physical phantom and obtain volumes that are comparable to those from physically determined means. The algorithm segments volumes with an error of within 13% as determined using a physical phantom. Our original work in fetal cardiac segmentation compares automatic and manual tracings to a physical phantom and also measures inter observer variation.

Assessment of left atrial mechanical functions and atrial electromechanical delay in Juvenile idiopathic arthritis by tissue Doppler echocardiography.

PubMed

El Eraky, Azza Z; Handoka, Nesrin M; Ghaly, Mona Sayed; Nasef, Samah Ismail; Eldahshan, Nahed A; Ibrahim, Ahmed M; Shalaby, Sherein

2016-11-24

Juvenile idiopathic arthritis (JIA) is a systemic chronic inflammatory disease. Studies using tissue Doppler imaging (TDI) for the evaluation of cardiac functions of children with JIA are limited. Thus, this study was conducted to evaluate Left ventricular function, left atrial mechanical functions and atrial electromechanical delay in JIA. This study was carried out as a across sectional study. A total of 34 patients with active JIA and 34 controls were included. Atrial electromechanical delay and left atrial (LA) mechanical functions in addition to systolic and diastolic left ventricular (LV) functions were measured by using conventional echocardiography and TDI. Assessment of disease activity was done using Juvenile arthritis disease activity score (JADAS-27). JIA patients had abnormal atrial electromechanical coupling as established from prolonged lateral mitral annulus (PA lateral), septal mitral annulus (PA septum), inter-atrial and intra-atrial electromechanical delays compared with healthy controls. Left ventricular filling abnormalities were found characterized by a reduced E/A ratio (1.07 ± 0.56 vs. 1.48 ± 0.16, p = 0.01). E/Em was significantly higher in patients with JIA (7.58 ± 1.79 vs. 4.74 ± 1.45, p = 0.003) denoting impaired diastolic function. Left atrial mechanical functions assessment showed significantly decreased LA passive emptying fraction, increased LA active emptying fraction and LA total emptying volume in JIA patients (p = 0.01, p = 0.01, p = 0.03 respectively). Atrial electromechanical coupling intervals, and LA mechanical functions were impaired which can be considered as an early form of subclinical cardiac involvement in JIA patients. Significant diastolic functional abnormalities exist in JIA.

Assessment of global and regional left ventricular function using 64-slice multislice computed tomography and 2D echocardiography: a comparison with cardiac magnetic resonance.

PubMed

Annuar, Bin Rapaee; Liew, Chee Khoon; Chin, Sze Piaw; Ong, Tiong Kiam; Seyfarth, M Tobias; Chan, Wei Ling; Fong, Yean Yip; Ang, Choon Kiat; Lin, Naing; Liew, Houng Bang; Sim, Kui Hian

2008-01-01

To compare the assessment of global and regional left ventricular (LV) function using 64-slice multislice computed tomography (MSCT), 2D echocardiography (2DE) and cardiac magnetic resonance (CMR). Thirty-two consecutive patients (mean age, 56.5+/-9.7 years) referred for evaluation of coronary artery using 64-slice MSCT also underwent 2DE and CMR within 48h. The global left ventricular function which include left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (LVdV) and left ventricular end systolic volume (LVsV) were determine using the three modalities. Regional wall motion (RWM) was assessed visually in all three modalities. The CMR served as the gold standard for the comparison between 64-slice MSCT with CMR and 2DE with CMR. Statistical analysis included Pearson correlation coefficient, Bland-Altman plots and kappa-statistics. The 64-slice MSCT agreed well with CMR for assessment of LVEF (r=0.92; p<0.0001), LVdV (r=0.98; p<0.0001) and LVsV (r=0.98; p<0.0001). In comparison with 64-slice MSCT, 2DE showed moderate correlation with CMR for the assessment of LVEF (r=0.84; p<0.0001), LVdV (r=0.83; p<0.0001) and LVsV (r=0.80; p<0.0001). However in RWM analysis, 2DE showed better accuracy than 64-slice MSCT (94.3% versus 82.4%) and closer agreement (kappa=0.89 versus 0.63) with CMR. 64-Slice MSCT correlates strongly with CMR in global LV function however in regional LV function 2DE showed better agreement with CMR than 64-slice MSCT.

Use of radiotelemetry to assess perinatal cardiac function in the ovine fetus and newborn.

PubMed

Antolic, A; Wood, C E; Keller-Wood, M

2017-12-01

The late gestation fetal ECG (fECG) has traditionally been difficult to characterize due to the low fECG signal relative to high maternal noise. Although new technologies have improved the feasibility of its acquisition and separation, little is known about its development in late gestation, a period in which the fetal heart undergoes extensive maturational changes. Here, we describe a method for the chronic implantation of radiotelemetry devices into late gestation ovine fetuses to characterize parameters of the fECG following surgery, throughout late gestation, and in the perinatal period. We found no significant changes in mean aortic pressure (MAP), heart rate (HR), or ECG in the 5 days following implantation; however, HR decreased in the first 24 h following the end of surgery, with associated increases in RR, PR, and QRS intervals. Over the last 14 days of fetal life, fetal MAP significantly increased, and HR significantly decreased, as expected. MAP and HR increased as labor progressed. Although there were no significant changes over time in the ECG during late gestation, the duration of the PR interval initially decreased and then increased as birth approached. These results indicate that although critical maturational changes occur in the late gestation fetal myocardium, the mechanisms that control the cardiac conduction are relatively mature in late gestation. The study demonstrates that radiotelemetry can be successfully used to assess fetal cardiac function, in particular conduction, through the process of labor and delivery, and may therefore be a useful tool for study of peripartum cardiac events. Copyright © 2017 the American Physiological Society.

Fast left ventricle tracking in CMR images using localized anatomical affine optical flow

NASA Astrophysics Data System (ADS)

Queirós, Sandro; Vilaça, João. L.; Morais, Pedro; Fonseca, Jaime C.; D'hooge, Jan; Barbosa, Daniel

2015-03-01

In daily cardiology practice, assessment of left ventricular (LV) global function using non-invasive imaging remains central for the diagnosis and follow-up of patients with cardiovascular diseases. Despite the different methodologies currently accessible for LV segmentation in cardiac magnetic resonance (CMR) images, a fast and complete LV delineation is still limitedly available for routine use. In this study, a localized anatomically constrained affine optical flow method is proposed for fast and automatic LV tracking throughout the full cardiac cycle in short-axis CMR images. Starting from an automatically delineated LV in the end-diastolic frame, the endocardial and epicardial boundaries are propagated by estimating the motion between adjacent cardiac phases using optical flow. In order to reduce the computational burden, the motion is only estimated in an anatomical region of interest around the tracked boundaries and subsequently integrated into a local affine motion model. Such localized estimation enables to capture complex motion patterns, while still being spatially consistent. The method was validated on 45 CMR datasets taken from the 2009 MICCAI LV segmentation challenge. The proposed approach proved to be robust and efficient, with an average distance error of 2.1 mm and a correlation with reference ejection fraction of 0.98 (1.9 +/- 4.5%). Moreover, it showed to be fast, taking 5 seconds for the tracking of a full 4D dataset (30 ms per image). Overall, a novel fast, robust and accurate LV tracking methodology was proposed, enabling accurate assessment of relevant global function cardiac indices, such as volumes and ejection fraction

Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death.

PubMed

Fischer, D; Rossa, S; Landmesser, U; Spiekermann, S; Engberding, N; Hornig, B; Drexler, H

2005-01-01

Endothelial dysfunction of coronary and peripheral arteries has been demonstrated in patients with chronic heart failure (CHF) and appears to be associated with functional implications. However, it is unknown whether endothelial dysfunction in CHF is independently associated with impaired outcome or progression of the disease. We assessed the follow-up of 67 consecutive patients with CHF [New York Heart Association (NYHA) functional class II-III] in which flow-dependent, endothelium-mediated vasodilation (FDD) of the radial artery was assessed by high resolution ultrasound. The primary endpoint was defined by cardiac death, hospitalization due to worsening of heart failure (NYHA class IV, pulmonary oedema), or heart transplantation. Cox regression analysis was used to determine whether FDD was associated with these heart failure-related events. During a median follow-up of 45.7 months 24 patients had an event: 18 patients were hospitalized due to worsening of heart failure or heart transplantation, six patients died for cardiac reasons. Cox regression analysis demonstrated that FDD (P<0.01), diabetes mellitus (P<0.01), and ejection fraction (P<0.01) were independent predictive factors for the occurrence of the primary endpoint. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with FDD above the median (6.2%) compared with those with FDD below the median (P<0.013). These observations suggest that endothelium-mediated vasodilation represents an independent predictor of cardiac death and hospitalization in patients with CHF, consistent with the notion that endothelium-derived nitric oxide may play a protective role in heart failure.

Impaired in vivo mitochondrial Krebs cycle activity after myocardial infarction assessed using hyperpolarized magnetic resonance spectroscopy.

PubMed

Dodd, Michael S; Atherton, Helen J; Carr, Carolyn A; Stuckey, Daniel J; West, James A; Griffin, Julian L; Radda, George K; Clarke, Kieran; Heather, Lisa C; Tyler, Damian J

2014-11-01

Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Using hyperpolarized carbon-13 ((13)C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased (13)C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. © 2014 American Heart Association, Inc.

Impaired In Vivo Mitochondrial Krebs Cycle Activity After Myocardial Infarction Assessed Using Hyperpolarized Magnetic Resonance Spectroscopy

PubMed Central

Carr, Carolyn A.; Stuckey, Daniel J.; West, James A.; Griffin, Julian L.; Radda, George K.; Clarke, Kieran; Heather, Lisa C.; Tyler, Damian J.

2015-01-01

Background Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Methods and Results Using hyperpolarized carbon-13 (13C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased 13C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. Conclusions The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. PMID:25201905

Restoration of Cardiac Tissue Thyroid Hormone Status in Experimental Hypothyroidism: A Dose-Response Study in Female Rats

PubMed Central

Weltman, Nathan Y.; Ojamaa, Kaie; Savinova, Olga V.; Chen, Yue-Feng; Schlenker, Evelyn H.; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Pol, Christine J.

2013-01-01

Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine whether the administration of T3 (instead of T4) improves the relationship between THs in serum and cardiac tissue and cardiac function over a short-term treatment period. Adult female Sprague Dawley rats were made hypothyroid by 7 weeks treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU). After establishing hypothyroidism, rats were assigned to 1 of 5 graded T3 dosages plus PTU for a 2-week dose-response experiment. Untreated, age-matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T3 and T4 levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene reexpression, and cardiac dysfunction. Short-term administration of T3 led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T3 levels was not associated with restoration of cardiac tissue T3 levels or cardiac function. In fact, a 3-fold higher T3 dosage was necessary to normalize cardiac tissue T3 levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states. PMID:23594789

Impact of High-Intensity-NIV on the heart in stable COPD: a randomised cross-over pilot study.

PubMed

Duiverman, Marieke Leontine; Maagh, Petra; Magnet, Friederike Sophie; Schmoor, Claudia; Arellano-Maric, Maria Paola; Meissner, Axel; Storre, Jan Hendrik; Wijkstra, Peter Jan; Windisch, Wolfram; Callegari, Jens

2017-05-02

Although high-intensity non-invasive ventilation has been shown to improve outcomes in stable COPD, it may adversely affect cardiac performance. Therefore, the aims of the present pilot study were to compare cardiac and pulmonary effects of 6 weeks of low-intensity non-invasive ventilation and 6 weeks of high-intensity non-invasive ventilation in stable COPD patients. In a randomised crossover pilot feasibility study, the change in cardiac output after 6 weeks of each NIV mode compared to baseline was assessed with echocardiography in 14 severe stable COPD patients. Furthermore, CO during NIV, gas exchange, lung function, and health-related quality of life were investigated. Three patients dropped out: two deteriorated on low-intensity non-invasive ventilation, and one presented with decompensated heart failure while on high-intensity non-invasive ventilation. Eleven patients were included in the analysis. In general, cardiac output and NTproBNP did not change, although individual effects were noticed, depending on the pressures applied and/or the co-existence of heart failure. High-intensity non-invasive ventilation tended to be more effective in improving gas exchange, but both modes improved lung function and the health-related quality of life. Long-term non-invasive ventilation with adequate pressure to improve gas exchange and health-related quality of life did not have an overall adverse effect on cardiac performance. Nevertheless, in patients with pre-existing heart failure, the application of very high inspiratory pressures might reduce cardiac output. The trial was registered in the Deutsches Register Klinischer Studien (DRKS-ID: DRKS00007977 ).

Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

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

Tal, A.; Leiberman, A.; Margulis, G.

Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4%more » (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present.« less

Assessing cardiac physical examination skills using simulation technology and real patients: a comparison study.

PubMed

Hatala, Rose; Issenberg, S Barry; Kassen, Barry; Cole, Gary; Bacchus, C Maria; Scalese, Ross J

2008-06-01

High-stakes assessments of doctors' physical examination skills often employ standardised patients (SPs) who lack physical abnormalities. Simulation technology provides additional opportunities to assess these skills by mimicking physical abnormalities. The current study examined the relationship between internists' cardiac physical examination competence as assessed with simulation technology compared with that assessed with real patients (RPs). The cardiac physical examination skills and bedside diagnostic accuracy of 28 internists were assessed during an objective structured clinical examination (OSCE). The OSCE included 3 modalities of cardiac patients: RPs with cardiac abnormalities; SPs combined with computer-based, audio-video simulations of auscultatory abnormalities, and a cardiac patient simulator (CPS) manikin. Four cardiac diagnoses and their associated cardiac findings were matched across modalities. At each station, 2 examiners independently rated a participant's physical examination technique and global clinical competence. Two investigators separately scored diagnostic accuracy. Inter-rater reliability between examiners for global ratings (GRs) ranged from 0.75-0.78 for the different modalities. Although there was no significant difference between participants' mean GRs for each modality, the correlations between participants' performances on each modality were low to modest: RP versus SP, r = 0.19; RP versus CPS, r = 0.22; SP versus CPS, r = 0.57 (P < 0.01). Methodological limitations included variability between modalities in the components contributing to examiners' GRs, a paucity of objective outcome measures and restricted case sampling. No modality provided a clear 'gold standard' for the assessment of cardiac physical examination competence. These limitations need to be addressed before determining the optimal patient modality for high-stakes assessment purposes.

Optogenetics-enabled assessment of viral gene and cell therapy for restoration of cardiac excitability

PubMed Central

Ambrosi, Christina M.; Boyle, Patrick M.; Chen, Kay; Trayanova, Natalia A.; Entcheva, Emilia

2015-01-01

Multiple cardiac pathologies are accompanied by loss of tissue excitability, which leads to a range of heart rhythm disorders (arrhythmias). In addition to electronic device therapy (i.e. implantable pacemakers and cardioverter/defibrillators), biological approaches have recently been explored to restore pacemaking ability and to correct conduction slowing in the heart by delivering excitatory ion channels or ion channel agonists. Using optogenetics as a tool to selectively interrogate only cells transduced to produce an exogenous excitatory ion current, we experimentally and computationally quantify the efficiency of such biological approaches in rescuing cardiac excitability as a function of the mode of application (viral gene delivery or cell delivery) and the geometry of the transduced region (focal or spatially-distributed). We demonstrate that for each configuration (delivery mode and spatial pattern), the optical energy needed to excite can be used to predict therapeutic efficiency of excitability restoration. Taken directly, these results can help guide optogenetic interventions for light-based control of cardiac excitation. More generally, our findings can help optimize gene therapy for restoration of cardiac excitability. PMID:26621212

[Radiation-related heart toxicity: Update in women].

PubMed

Marlière, S; Vautrin, E; Saunier, C; Chaikh, A; Gabelle-Flandin, I

2016-12-01

Breast cancer is a common diagnosis in women and thus women are at risk of radiation-induced heart disease, in particular during radiotherapy for left breast cancer and when the internal mammary chain is included. Rates of major cardiac events increase with younger age at the time of irradiation, diagnosis before 1990s, higher radiation doses, coexisting cardiovascular risk factors and adjuvant cardiotoxic chemotherapy. Radiation-induced heart disease comprises a spectrum of cardiac pathologies, including pericardial disease, cardiomyopathy, coronary artery disease and valvular disease. The cardiac injury can appear a long time after radiotherapy and can consist of complex lesions with poor prognosis. The disciplines of cardiology and oncology have increasingly recognized the benefits of collaborating in the care of cancer patients with cardiac disease, developing guidelines for the assessment and management of radiation-related cardiovascular disease. We could consider screening patients with previous chest radiation every 5 years with transthoracic echocardiography and functional imaging. However, prevention remains the primary goal, using cardiac sparing doses and avoidance techniques in radiotherapy to improve patient survival. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

3D bioprinted functional and contractile cardiac tissue constructs

PubMed Central

Wang, Zhan; Lee, Sang Jin; Cheng, Heng-Jie; Yoo, James J.; Atala, Anthony

2018-01-01

Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However, its applications remain limited because the cardiac tissue is a highly organized structure with unique physiologic, biomechanical, and electrical properties. In this study, we undertook a proof-of-concept study to develop a contractile cardiac tissue with cellular organization, uniformity, and scalability by using three-dimensional (3D) bioprinting strategy. Primary cardiomyocytes were isolated from infant rat hearts and suspended in a fibrin-based bioink to determine the priting capability for cardiac tissue engineering. This cell-laden hydrogel was sequentially printed with a sacrificial hydrogel and a supporting polymeric frame through a 300-μm nozzle by pressured air. Bioprinted cardiac tissue constructs had a spontaneous synchronous contraction in culture, implying in vitro cardiac tissue development and maturation. Progressive cardiac tissue development was confirmed by immunostaining for α-actinin and connexin 43, indicating that cardiac tissues were formed with uniformly aligned, dense, and electromechanically coupled cardiac cells. These constructs exhibited physiologic responses to known cardiac drugs regarding beating frequency and contraction forces. In addition, Notch signaling blockade significantly accelerated development and maturation of bioprinted cardiac tissues. Our results demonstrated the feasibility of bioprinting functional cardiac tissues that could be used for tissue engineering applications and pharmaceutical purposes. PMID:29452273

Long-term functional and echocardiographic assessment after penetrating cardiac injury: 5-year follow-up results.

PubMed

Carr, John Alfred; Buterakos, Roxanne; Bowling, William M; Janson, Lisa; Kralovich, Kurt A; Copeland, Craig; Link, Renee; Roiter, Cecilia; Casey, Gregory; Wagner, James W

2011-03-01

There is almost no data describing the long-term functional outcome of patients after penetrating cardiac injury. A retrospective study at a Level I trauma center from 2000 to 2009. Sixty-three patients had penetrating cardiac injuries from 28 stabbings and 35 gunshots. Men comprised 89% (56) of the patients. Overall, there were 21 survivors (33%) and 42 died in the emergency room or perioperative period. The mean age did not significantly differ between survivors (36 years ± 12 years) compared with those who died (30 years ± 11 years; p=0.07). There was an increased chance of survival after being stabbed compared with being shot (17 patients vs. 4 patients; odds ratio=12; p=0.002). Thirteen (62%) had injuries to the right ventricle only. Three patients died during follow-up: one from lung cancer and two other patients died from myocardial infarctions, one 9 years later at the age of 45 years and the other 8 years later at the age of 55 years. The survivors had functional follow-up evaluations from 2 months to 114 months (median, 71; interquartile range, 34-92 months) and echocardiographic follow-up from 2 months to 107 months (median, 64; interquartile range, 31-84 months) after their injuries. Functionally, all patients were in NYHA class 1 status, except one patient in class II who was 54 years old and had a mild exertional limitation. The previously injured area could only be identified by echocardiogram in one patient who had a patch repair of a ventricular septal defect (VSD). The mean ejection fraction improved over time from a mean of 51% ± 8% in the immediate postoperative period to 60% ± 9% after a mean follow-up of 59 months (p=0.01). After surgery, 43% of patients had a mild to moderate pericardial effusion; however, the long-term follow-up studies showed that all these had resolved. Wall motion abnormalities occurred in 33% of patients in the immediate postoperative period and, again, all these resolved during long-term follow-up. Patients who survive penetrating cardiac injuries, without coronary arterial or valvular disruption, have an excellent long-term functional outcome with minimal subsequent cardiac morbidity related to the injury. Full physiologic recovery and normal cardiac function can be expected if the patient survives. Copyright © 2011 by Lippincott Williams & Wilkins

Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

PubMed Central

See Hoe, Louise E.; Schilling, Jan M.; Tarbit, Emiri; Kiessling, Can J.; Busija, Anna R.; Niesman, Ingrid R.; Du Toit, Eugene; Ashton, Kevin J.; Roth, David M.; Headrick, John P.; Patel, Hemal H.

2014-01-01

Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-β-cyclodextrin (MβCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused hearts from young male C57Bl/6 mice were untreated or treated with 0.02–1.0 mM MβCD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective effects of morphine applied either acutely or chronically [sustained ligand-activated preconditioning (SLP)] were assessed. MβCD concentration dependently reduced normoxic contractile function and postischemic outcomes in association with graded (10–30%) reductions in sarcolemmal cholesterol. Cardioprotection with acute morphine was abolished with ≥20 μM MβCD, whereas SLP was more robust and only inhibited with ≥200 μM MβCD. Deletion of Cav-3 also reduced, whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained equally effective in Cav-3 KO mice and was additive with innate protection arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression. PMID:25063791

Differential and Conditional Activation of PKC-Isoforms Dictates Cardiac Adaptation during Physiological to Pathological Hypertrophy

PubMed Central

Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha

2014-01-01

A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID:25116170

Echocardiographic Techniques of Deformation Imaging in the Evaluation of Maternal Cardiovascular System in Patients with Complicated Pregnancies.

PubMed

Visentin, Silvia; Palermo, Chiara; Camerin, Martina; Daliento, Luciano; Muraru, Denisa; Cosmi, Erich; Badano, Luigi P

2017-01-01

Cardiovascular diseases (CVD) represent the leading cause of maternal mortality and morbidity. Knowledge of CVD in women is constantly evolving and data are emerging that female-specific risk factors as complications of pregnancy are conditions associated with an increased risk for the long-term development of CVD. Echocardiography is a safe and effective imaging technique indicated in symptomatic or asymptomatic pregnant women with congenital heart diseases who require close monitoring of cardiac function. Deformation imaging is an echocardiographic technique used to assess myocardial function by measuring the actual deformation of the myocardium through the cardiac cycle. Speckle-tracking echocardiography (STE) is a two-dimensional (2D) technique which has been found to be more accurate than tissue Doppler to assess both left ventricular (LV) and right ventricular (RV) myocardial function. The use of 2D STE however might present some technical issues due to the tomographic nature of the technique and the motion in the three-dimensional space of the myocardial speckles. This has promoted the use of 3D STE to track the motion of the speckles in the 3D space. This review will focus on the clinical value of the new echocardiographic techniques of deformation imaging used to assess the maternal cardiovascular system in complicated pregnancies.

Pulmonary arterial stiffening in COPD and its implications for right ventricular remodelling.

PubMed

Weir-McCall, Jonathan R; Liu-Shiu-Cheong, Patrick Sk; Struthers, Allan D; Lipworth, Brian J; Houston, J Graeme

2018-02-27

Pulmonary pulse wave velocity (PWV) allows the non-invasive measurement of pulmonary arterial stiffening, but has not previously been assessed in COPD. The aim of the current study was to assess PWV in COPD and its association with right ventricular (RV) remodelling. Fifty-eight participants with COPD underwent pulmonary function tests, 6-min walk test and cardiac MRI, while 21 healthy controls (HCs) underwent cardiac MRI. Thirty-two COPD patients underwent a follow-up MRI to assess for longitudinal changes in RV metrics. Cardiac MRI was used to quantify RV mass, volumes and PWV. Differences in continuous variables between the COPD and HC groups was tested using an independent t-test, and associations between PWV and right ventricular parameters was examined using Pearson's correlation coefficient. Those with COPD had reduced pulsatility (COPD (mean±SD):24.88±8.84% vs. HC:30.55±11.28%, p=0.021), pulmonary acceleration time (COPD:104.0±22.9ms vs. HC: 128.1±32.2ms, p<0.001), higher PWV (COPD:2.62±1.29ms -1 vs. HC:1.78±0.72ms -1 , p=0.001), lower RV end diastolic volume (COPD:53.6±11.1ml vs. HC:59.9±13.0ml, p=0.037) and RV stroke volume (COPD:31.9±6.9ml/m 2 vs. HC:37.1±6.2ml/m 2 , p=0.003) with no difference in mass (p=0.53). PWV was not associated with right ventricular parameters. While pulmonary vascular remodelling is present in COPD, cardiac remodelling favours reduced filling rather than increased afterload. Treatment of obstructive lung disease may have greater effect on cardiac function than treatment of pulmonary vascular disease in most COPD patients KEY POINTS: • Pulmonary pulse wave velocity (PWV) is elevated in COPD. • Pulmonary PWV is not associated with right ventricular remodelling. • Right ventricular remodelling is more in keeping with that of reduced filling.

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

PubMed

Liu, Zhong-wei; Wang, Jun-kui; Qiu, Chuan; Guan, Gong-chang; Liu, Xin-hong; Li, Shang-jian; Deng, Zheng-rong

2015-03-01

Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

Associations of childhood and adult obesity with left ventricular structure and function.

PubMed

Yang, H; Huynh, Q L; Venn, A J; Dwyer, T; Marwick, T H

2017-04-01

Overweight and obesity are associated with left ventricular (LV) dysfunction. We sought whether echocardiographic evidence of abnormal adult cardiac structure and function was related to childhood or adult adiposity. This study included 159 healthy individuals aged 7-15 years and followed until age 36-45 years. Anthropometric measurements were performed both at baseline and follow-up. Cardiac structure (indexed left atrial volume (LAVi), left ventricular mass (LVMi)) and LV function (global longitudinal strain (GLS), mitral e') were assessed using standard echocardiography at follow-up. Conventional cutoffs were used to define abnormal LAVi, LVMi, GLS and mitral annular e'. Childhood body mass index (BMI) was correlated with LVMi (r=0.25, P=0.002), and child waist circumference was correlated with LVMi (r=0.18, P=0.03) and LAVi (r=0.20, P=0.01), but neither were correlated with GLS. One s.d. (by age and sex) increase in childhood BMI was associated with LV hypertrophy (relative risk: 2.04 (95% confidence interval (CI): 1.09, 3.78)) and LA enlargement (relative risk: 1.81 (95% CI: 1.02, 3.21)) independent of adult BMI, but the association was not observed with impaired GLS or mitral e'. Cardiac functional measures were more impaired in those who had normal BMI as child, but had high BMI in adulthood (P<0.03), and not different in those who were overweight or obese as a child and remained so in adulthood (P>0.33). Childhood adiposity is independently associated with structural cardiac disturbances (LVMi and LAVi). However, functional alterations (GLS and mitral e') were more frequently associated with adult overweight or obesity, independent of childhood adiposity.

Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia.

PubMed

Elkina, Yulia; Palus, Sandra; Tschirner, Anika; Hartmann, Kai; von Haehling, Stephan; Doehner, Wolfram; Mayer, Ulrike; Coats, Andrew J S; Beadle, John; Anker, Stefan D; Springer, Jochen

2013-12-10

Cancer cachexia is thought to be the cause of >20% of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia. The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1mg/kg/d (LD), 10mg/kg/d (HD) tandospirone or placebo. Weight, body composition (NMR), cardiac function (echocardiography), activity and food intake were assessed. Noradrenalin and cortisol were measured in plasma and caspase activity in skeletal muscle. Ten mg/kg/d tandospirone decreased the loss of body weight (p=0.0003) compared to placebo animals, mainly due to preservation of muscle mass (p<0.001), while 1mg/kg/d tandospirone was not effective. Locomotor activity (p=0.0007) and food intake (p=0.0001) were increased by HD tandospirone. The weight (p=0.0277) and function of heart (left ventricular mass, fractional shortening, stroke volume, ejection fraction, all p<0.05) were significantly improved. In the HD tandospirone group, plasma levels of noradrenalin and cortisol were significantly reduced by 49% and 52%, respectively, which may have contributed to the lower caspase activity in the gastrocnemius muscle. Most importantly, HD tandospirone significantly improved survival compared to placebo rats (HR: 0.34; 95% CI: 0.13-0.86; p=0.0495). Tandospirone showed significant beneficial effects in the Yoshida hepatoma cancer cachexia model and should be further examined as a prospective drug for this syndrome. © 2013.

Functional optical coherence tomography for live dynamic analysis of mouse embryonic cardiogenesis

NASA Astrophysics Data System (ADS)

Wang, Shang; Lopez, Andrew L.; Larina, Irina V.

2018-02-01

Blood flow, heart contraction, and tissue stiffness are important regulators of cardiac morphogenesis and function during embryonic development. Defining how these factors are integrated is critically important to advance prevention, diagnostics, and treatment of congenital heart defects. Mammalian embryonic development is taking place deep within the female body, which makes cardiodynamic imaging and analysis during early developmental stages in humans inaccessible. With thousands of mutant lines available and well-established genetic manipulation tools, mouse is a great model to understand how biomechanical factors are integrated with molecular pathways to regulate cardiac function and development. Dynamic imaging and quantitative analysis of the biomechanics of live mouse embryos have become increasingly important, which demands continuous advancements in imaging techniques and live assessment approaches. This has been one of the major drives to keep pushing the frontier of embryonic imaging for better resolution, higher speed, deeper penetration, and more diverse and effective contrasts. Optical coherence tomography (OCT) has played a significant role in addressing such demands, and its features in non-labeling imaging, 3D capability, a large working distance, and various functional derivatives allow OCT to cover a number of specific applications in embryonic imaging. Recently, our group has made several technical improvements in using OCT to probe the biomechanical aspects of live developing mouse embryos at early stages. These include the direct volumetric structural and functional imaging of the cardiodynamics, four-dimensional quantitative Doppler imaging and analysis of the cardiac blood flow, and fourdimensional blood flow separation from the cardiac wall tissue in the beating embryonic heart. Here, we present a short review of these studies together with brief descriptions of the previous work that demonstrate OCT as a valuable and useful imaging tool for the research in developmental cardiology.

The effect of time to defibrillation and targeted temperature management on functional survival after out-of-hospital cardiac arrest.

PubMed

Drennan, Ian R; Lin, Steve; Thorpe, Kevin E; Morrison, Laurie J

2014-11-01

Cardiac arrest physiology has been proposed to occur in three distinct phases: electrical, circulatory and metabolic. There is limited research evaluating the relationship of the 3-phase model of cardiac arrest to functional survival at hospital discharge. Furthermore, the effect of post-cardiac arrest targeted temperature management (TTM) on functional survival during each phase is unknown. To determine the effect of TTM on the relationship between the time of initial defibrillation during each phase of cardiac arrest and functional survival at hospital discharge. This was a retrospective observational study of consecutive adult (≥18 years) out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythms. Included patients obtained a return of spontaneous circulation (ROSC) and were eligible for TTM. Multivariable logistic regression was used to determine predictors of functional survival at hospital discharge. There were 20,165 OHCA treated by EMS and 871 patients were eligible for TTM. Of these patients, 622 (71.4%) survived to hospital discharge and 487 (55.9%) had good functional survival. Good functional survival was associated with younger age (OR 0.94; 95% CI 0.93-0.95), shorter times from collapse to initial defibrillation (OR 0.73; 95% CI 0.65-0.82), and use of post-cardiac arrest TTM (OR 1.49; 95% CI 1.07-2.30). Functional survival decreased during each phase of the model (65.3% vs. 61.7% vs. 50.2%, P<0.001). Functional survival at hospital discharge was associated with shorter times to initial defibrillation and was decreased during each successive phase of the 3-phase model. Post-cardiac arrest TTM was associated with improved functional survival. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Methodological Gaps in Left Atrial Function Assessment by 2D Speckle Tracking Echocardiography

PubMed Central

Rimbaş, Roxana Cristina; Dulgheru, Raluca Elena; Vinereanu, Dragoş

2015-01-01

The assessment of left atrial (LA) function is used in various cardiovascular diseases. LA plays a complementary role in cardiac performance by modulating left ventricular (LV) function. Transthoracic two-dimensional (2D) phasic volumes and Doppler echocardiography can measure LA function non-invasively. However, evaluation of LA deformation derived from 2D speckle tracking echocardiography (STE) is a new feasible and promising approach for assessment of LA mechanics. These parameters are able to detect subclinical LA dysfunction in different pathological condition. Normal ranges for LA deformation and cut-off values to diagnose LA dysfunction with different diseases have been reported, but data are still conflicting, probably because of some methodological and technical issues. This review highlights the importance of an unique standardized technique to assess the LA phasic functions by STE, and discusses recent studies on the most important clinical applications of this technique. PMID:26761370

Cardiac function in children with premature ventricular contractions: the effect of omega-3 polyunsaturated fatty acid supplementation.

PubMed

Oner, Taliha; Ozdemir, Rahmi; Doksöz, Onder; Genc, Dildar B; Guven, Baris; Demirpence, Savas; Yilmazer, Murat M; Yozgat, Yilmaz; Mese, Timur; Tavli, Vedide

2018-07-01

Premature ventricular contractions are accepted as benign in structurally normal hearts. However, reversible cardiomyopathy can sometimes develop. Omega-3 polyunsaturated fatty acids have anti-arrhythmic properties in animals and humans.AimWe evaluated left ventricular function in children with premature ventricular contractions with normal cardiac anatomy and assessed the impact of omega-3 fatty acid supplementation on left ventricular function in a prospective trial. A total of 25 patients with premature ventricular contraction, with more than 2% premature ventricular contractions on 24-hour Holter electrocardiography, and 30 healthy patients were included into study. All patients underwent electrocardiography, left ventricular M-mode echocardiography, and myocardial performance index testing. Patients with premature ventricular contraction were given omega-3 fatty acids at a dose of 1 g/day for 3 months, and control echocardiography and 24-hour Holter electrocardiography were performed. Neither placebo nor omega-3 fatty acids were given to the control group. Compared with the values of the control group, the patients with premature ventricular contraction had significantly lower fractional shortening. The myocardial performance index decreased markedly in the patient groups. The mean heart rate and mean premature ventricular contraction percentage of Group 2 significantly decreased in comparison with their baseline values after the omega-3 supplementation. In conclusion, premature ventricular contractions can lead to systolic cardiac dysfunction in children. Omega-3 supplementation may improve cardiac function in children with premature ventricular contractions. This is the first study conducted in children to investigate the possible role of omega-3 fatty acid supplementation on treatment of premature ventricular contractions.

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

Hu Shunying; Chen Yundai; Li Libing

Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrastmore » echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +- 9.01 vs. 41.94 +- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +- 1303 vs. 1667 +- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +- 1084 vs. 1566 +- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.« less

Reduction of physical activity in daily life and its determinants in smokers without airflow obstruction.

PubMed

Furlanetto, Karina Couto; Mantoani, Leandro Cruz; Bisca, Gianna; Morita, Andrea Akemi; Zabatiero, Juliana; Proença, Mahara; Kovelis, Demétria; Pitta, Fabio

2014-04-01

In smokers without airflow obstruction, detailed, objective and controlled quantification of the level of physical inactivity in daily life has never been performed. This study aimed to objectively assess the level of physical activity in daily life in adult smokers without airflow obstruction in comparison with matched non-smokers, and to investigate the determinants for daily physical activity in smokers. Sixty smokers (aged 50 (39-54) years) and 50 non-smokers (aged 48 (40-53) years) matched for gender, age, anthropometric characteristics, educational level, employment status and seasons of the year assessment period were cross-sectionally assessed regarding their daily physical activity with a step counter, besides assessment of lung function, functional exercise capacity, quality of life, anxiety, depression, self-reported comorbidities carbon monoxide level, nicotine dependence and smoking habits. When compared with non-smokers, smokers walked less in daily life (7923 ± 3558 vs 9553 ± 3637 steps/day, respectively), presented worse lung function, functional exercise capacity, quality of life, anxiety and depression. Multiple regression analyses identified functional exercise capacity, Borg fatigue, self-reported motivation/physical activity behaviour and cardiac disease as significant determinants of number of steps/day in smokers (partial r(2)  = 0.10, 0.12, 0.16 and 0.05; b = 15, -997, 1207 and -2330 steps/day, respectively; overall fit of the model R(2)  = 0.38; P < 0.001). Adult smokers without airflow obstruction presented reduced level of daily physical activity. Functional exercise capacity, extended fatigue sensation, aspects of motivation/physical activity behaviour and self-reported cardiac disease are significant determinants of physical activity in daily life in smokers. © 2014 The Authors. Respirology © 2014 Asian Pacific Society of Respirology.

Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis

PubMed Central

Haller, Steven T.; Fan, Xiaoming; Xie, Jeffrey X.; Kennedy, David J.; Liu, Jiang; Yan, Yanling; Hernandez, Dawn-Alita; Mathew, Denzil P.; Cooper, Christopher J.; Shapiro, Joseph I.; Tian, Jiang

2016-01-01

Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0.05) decreased renal and cardiac expression of the antifibrotic microRNA miR-29b-3 and increased expression of molecular fibrosis markers. In terms of cardiac and renal organ structure and function, exposure to cigarette smoke led to significantly increased systolic blood pressure, cardiac hypertrophy, cardiac and renal fibrosis, and decreased renal function. These data indicate that decreased expression of miR-29b-3p is a novel mechanism wherein cigarette smoke promotes accelerated cardiac and renal tissue injury in CKD. (155 words) PMID:27789733

Megestrol acetate improves cardiac function in a model of cancer cachexia-induced cardiomyopathy by autophagic modulation.

PubMed

Musolino, Vincenzo; Palus, Sandra; Tschirner, Anika; Drescher, Cathleen; Gliozzi, Micaela; Carresi, Cristina; Vitale, Cristiana; Muscoli, Carolina; Doehner, Wolfram; von Haehling, Stephan; Anker, Stefan D; Mollace, Vincenzo; Springer, Jochen

2016-12-01

Cachexia is a complex metabolic syndrome associated with cancer. One of the features of cachexia is the loss of muscle mass, characterized by an imbalance between protein synthesis and protein degradation. Muscle atrophy is caused by the hyperactivation of some of the main cellular catabolic pathways, including autophagy. Cachexia also affects the cardiac muscle. As a consequence of the atrophy of the heart, cardiac function is impaired and mortality is increased. Anti-cachectic therapy in patients with cancer cachexia is so far limited to nutritional support and anabolic steroids. The use of the appetite stimulant megestrol acetate (MA) has been discussed as a treatment for cachexia. In this study the effects of MA were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). Rats were treated daily with 100 mg/kg of MA or placebo starting one day after tumour inoculation, and for a period of 16 days. Body weight and body composition were assessed at baseline and at the end of the study. Cardiac function was analysed by echocardiography at baseline and at day 11. Locomotor activity and food intake were assessed before tumour inoculation and at day 11. Autophagic markers were assessed in gastrocnemius muscle and heart by western blot analysis. Treatment with 100 mg/kg/day MA significantly attenuated the loss of body weight (-9 ± 12%, P  < 0.05) and the wasting of lean and fat mass (-7.0 ± 6% and -22.4 ± 3 %, P  < 0.001 and P  < 0.05, respectively). Administration of 100 mg/kg/day MA significantly protected the heart from general atrophy (633.8 ± 30 mg vs. placebo 474 ± 13 mg, P  < 0.001). Tumour-bearing rats displayed cardiac dysfunction, as indicated by the significant impairment of the left ventricular ejection fraction, the left ventricular fractional shortening, the stroke volume, the end dyastolic volume, and the end systolic volume. In contrast, MA significantly improved left ventricular ejection fraction, left ventricular fractional shortening, and left ventricular end systolic volume. Western blotting analysis showed an upregulation of the autophagic pathway in the gastrocnemius and hearts of the placebo-treated tumour-bearing rats. Treatment with MA, however, was able to modulate the autophagic markers (e.g. Beclin-1, p62, TRAF6, and LC3) in the gastrocnemius and in the hearts of tumour-bearing rats. Most importantly, 100 mg/kg/day MA reduced mortality [hazard ratio (HR): 0.44; 95%CI: 0.20-1.00; P  = 0.0486]. Megestrol acetate improved survival and reduced wasting through a marked downregulation of autophagy, occurring in both skeletal and heart muscle, the latter effect leading to a significant improvement of cardiac function. Our data suggest that MA might represent a valuable strategy to counteract the development of cancer cachexia-induced cardiomyopathy.

Longitudinal In Vivo SPECT/CT Imaging Reveals Morphological Changes and Cardiopulmonary Apoptosis in a Rodent Model of Pulmonary Arterial Hypertension

PubMed Central

Paffett, Michael L.; Hesterman, Jacob; Candelaria, Gabriel; Lucas, Selita; Anderson, Tamara; Irwin, Daniel; Hoppin, Jack; Norenberg, Jeffrey; Campen, Matthew J.

2012-01-01

Pulmonary arterial hypertension (PAH) has a complex pathogenesis involving both heart and lungs. Animal models can reflect aspects of the human pathology and provide insights into the development and underlying mechanisms of disease. Because of the variability of most animal models of PAH, serial in vivo measurements of cardiopulmonary function, morphology, and markers of pathology can enhance the value of such studies. Therefore, quantitative in vivo SPECT/CT imaging was performed to assess cardiac function, morphology and cardiac perfusion utilizing 201Thallium (201Tl) in control and monocrotaline-treated rats. In addition, lung and heart apoptosis was examined with 99mTc-Annexin V (99mTc-Annexin) in these cohorts. Following baseline imaging, rats were injected with saline or monocrotaline (50 mg/kg, i.p.) and imaged weekly for 6 weeks. To assess a therapeutic response in an established pulmonary hypertensive state, a cohort of rats received resveratrol in drinking water (3 mg/kg/day) on days 28–42 post-monocrotaline injection to monitor regression of cardiopulmonary apoptosis. PAH in monocrotaline-treated rats was verified by conventional hemodynamic techniques on day 42 (right ventricular systolic pressure (RSVP) = 66.2 mmHg in monocrotaline vs 28.8 mmHg in controls) and in terms of right ventricular hypertrophy (RV/LVS = 0.70 in monocrotaline vs 0.32 in controls). Resveratrol partially reversed both RVSP (41.4 mmHg) and RV/LVS (0.46), as well as lung edema and RV contractility +dP/dtmax. Serial 99mTc-Annexin V imaging showed clear increases in pulmonary and cardiac apoptosis when compared to baseline, which regressed following resveratrol treatment. Monocrotaline induced modest changes in whole-heart perfusion as assessed by 201TI imaging and cardiac morphological changes consistent with septal deviation and enlarged RV. This study demonstrates the utility of functional in vivo SPECT/CT imaging in rodent models of PAH and further confirms the efficacy of resveratrol in reversing established monocrotaline-induced PAH presumably by attenuation of cardiopulmonary apoptosis. PMID:22815866

A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice.

PubMed

Carbone, Salvatore; Mauro, Adolfo G; Mezzaroma, Eleonora; Kraskauskas, Donatas; Marchetti, Carlo; Buzzetti, Raffaella; Van Tassell, Benjamin W; Abbate, Antonio; Toldo, Stefano

2015-11-01

Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, exercise intolerance and cardiac dysfunction. Unhealthy diet has been associated with increased risk of obesity and heart disease, but whether it directly affects cardiac function, and promotes the development and progression of HF is unknown. We fed 8-week old male or female CD-1 mice with a standard diet (SD) or a diet rich in saturated fat and sugar, resembling a "Western" diet (WD). Cardiac systolic and diastolic function was measured at baseline and 4 and 8 weeks by Doppler echocardiography, and left ventricular (LV) end-diastolic pressure (EDP) by cardiac catheterization prior to sacrifice. An additional group of mice received WD for 4 weeks followed by SD (wash-out) for 8 weeks. WD-fed mice experienced a significant decreased in LV ejection fraction (LVEF), reflecting impaired systolic function, and a significant increase in isovolumetric relaxation time (IRT), myocardial performance index (MPI), and LVEDP, showing impaired diastolic function, without any sex-related differences. Switching to a SD after 4 weeks of WD partially reversed the cardiac systolic and diastolic dysfunction. A diet rich in saturated fat and sugars (WD) impairs cardiac systolic and diastolic function in the mouse. Further studies are required to define the mechanism through which diet affects cardiac function, and whether dietary interventions can be used in patients with, or at risk for, HF. Published by Elsevier Ireland Ltd.

Understanding the physiology of mindfulness: aortic hemodynamics and heart rate variability.

PubMed

May, Ross W; Bamber, Mandy; Seibert, Gregory S; Sanchez-Gonzalez, Marcos A; Leonard, Joseph T; Salsbury, Rebecca A; Fincham, Frank D

2016-01-01

Data were collected to examine autonomic and hemodynamic cardiovascular modulation underlying mindfulness from two independent samples. An initial sample (N = 185) underwent laboratory assessments of central aortic blood pressure and myocardial functioning to investigated the association between mindfulness and cardiac functioning. Controlling for religiosity, mindfulness demonstrated a strong negative relationship with myocardial oxygen consumption and left ventricular work but not heart rate or blood pressure. A second sample (N = 124) underwent a brief (15 min) mindfulness inducing intervention to examine the influence of mindfulness on cardiovascular autonomic modulation via blood pressure variability and heart rate variability. The intervention had a strong positive effect on cardiovascular modulation by decreasing cardiac sympathovagal tone, vasomotor tone, vascular resistance and ventricular workload. This research establishes a link between mindfulness and cardiovascular functioning via correlational and experimental methodologies in samples of mostly female undergraduates. Future directions for research are outlined.

Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

PubMed

Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

2017-08-01

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed in transgenic chronic heart failure mice, evaluated in the critical period between the occurrence of an impairment of cardiac function and the terminal stage of the disease. Exercise training improved exercise performance and cardiac function, but it did not affect the impaired mitochondrial respiration. Factors "upstream" of mitochondria, including an enhanced cardiovascular O 2 delivery, were mainly responsible for the functional improvement. Copyright © 2017 the American Physiological Society.

Wave intensity analysis in mice: an ultrasound-based study in the abdominal aorta and common carotid artery

NASA Astrophysics Data System (ADS)

Di Lascio, N.; Kusmic, C.; Stea, F.; Faita, F.

2017-03-01

Wave Intensity Analysis (WIA) can provide parameters representative of the interaction between the vascular network and the heart. It has been already demonstrated that WIA-derived biomarkes have a quantitative physiological meaning. Aim of this study was to develop an image process algorithm for performing non-invasive WIA in mice and correlate commonly used cardiac function parameters with WIA-derived indexes. Sixteen wild-type male mice (8 weeks-old) were imaged with high-resolution ultrasound (Vevo 2100). Abdominal aorta and common carotid pulse wave velocities (PWVabd, PWVcar) were obtained processing B-Mode and PW-Doppler images and employed to assess WIA. Amplitudes of the first (W1abd, W1car) and the second (W2abd, W2car) local maxima and minimum (Wbabd,Wbcar) were evaluated; areas under the negative part of the curve were also calculated (NAabd, NAcar). Cardiac output (CO), ejection fraction (EF) fractional shortening (FS) and stroke volume (SV) were estimated; strain analysis provided strain and strain rate values for longitudinal, radial and circumferential directions (LS, LSR, RS, RSR, CS, CSR). Isovolumetric relaxation time (IVRT) was calculated from mitral inflow PW-Doppler images; IVRT values were normalized for cardiac cycle length. W1abd was correlated with LS (R=0.65) and LSR (R=0.59), while W1car was correlated with CO (R=0.58), EF (R=0.72), LS (R=0.65), LSR (R=0.89), CS (R=0.71), CSR (R=0.70). Both W2abd and W2car were not correlated with IVRT. Carotid artery WIA-derived parameters are more representative of cardiac function than those obtained from the abdominal aorta. The described US-based method can provide information about cardiac function and cardio-vascular interaction simply studying a single vascular site.

Deep breathing exercises performed 2 months following cardiac surgery: a randomized controlled trial.

PubMed

Westerdahl, Elisabeth; Urell, Charlotte; Jonsson, Marcus; Bryngelsson, Ing-Liss; Hedenström, Hans; Emtner, Margareta

2014-01-01

Postoperative breathing exercises are recommended to cardiac surgery patients. Instructions concerning how long patients should continue exercises after discharge vary, and the significance of treatment needs to be determined. Our aim was to assess the effects of home-based deep breathing exercises performed with a positive expiratory pressure device for 2 months following cardiac surgery. The study design was a prospective, single-blinded, parallel-group, randomized trial. Patients performing breathing exercises 2 months after cardiac surgery (n = 159) were compared with a control group (n = 154) performing no breathing exercises after discharge. The intervention consisted of 30 slow deep breaths performed with a positive expiratory pressure device (10-15 cm H2O), 5 times a day, during the first 2 months after surgery. The outcomes were lung function measurements, oxygen saturation, thoracic excursion mobility, subjective perception of breathing and pain, patient-perceived quality of recovery (40-Item Quality of Recovery score), health-related quality of life (36-Item Short Form Health Survey), and self-reported respiratory tract infection/pneumonia and antibiotic treatment. Two months postoperatively, the patients had significantly reduced lung function, with a mean decrease in forced expiratory volume in 1 second to 93 ± 12% (P< .001) of preoperative values. Oxygenation had returned to preoperative values, and 5 of 8 aspects in the 36-Item Short Form Health Survey were improved compared with preoperative values (P< .01). There were no significant differences between the groups in any of the measured outcomes. No significant differences in lung function, subjective perceptions, or quality of life were found between patients performing home-based deep breathing exercises and control patients 2 months after cardiac surgery.

PREVALENCE OF POST-THROMBOTIC SYNDROME AFTER CARDIAC CATHETERIZATION

PubMed Central

Luceri, Michael J.; Tala, Joana A.; Weismann, Constance G.; Silva, Cicero T.; Faustino, E. Vincent S.

2015-01-01

BACKGROUND As the survival of children with cardiac disease increases, chronic complications of deep venous thrombosis from cardiac catheterization, particularly post-thrombotic syndrome, may be important to monitor for and treat, if needed. We aimed to determine the prevalence of this syndrome in children who underwent cardiac catheterization. PROCEDURE We conducted a cross-sectional study of children <18 years old at least 1 year from first catheterization through the femoral vein. We used the Manco-Johnson instrument, the only tool validated in children, to diagnose post-thrombotic syndrome. We defined the syndrome as a score ≥1. It was considered physically and functionally significant if the score was ≥1 in both physical and functional domains of the instrument. We also conducted ultrasonography to assess for thrombosis and valvular insufficiency. RESULTS We enrolled 62 children with a median age of 4 months during catheterization and a median of 5.4 years since catheterization. A total of 40 children had post-thrombotic syndrome (prevalence: 64.5%; 95% confidence interval: 51.3%–76.3%), the majority of which were mild. Presence of cyanotic congenital heart disease, total number of catheterizations, use of antithrombotic agents at any time after the first catheterization, age at first catheterization, or time since first catheterization was not associated with the syndrome. A total of 7 children (prevalence: 11.3%; 95% confidence interval: 3.2%–19.4%) had physically and functionally significant syndrome. None of the children had abnormalities on ultrasonography at the time of enrollment. CONCLUSIONS Post-thrombotic syndrome is a common complication after cardiac catheterization. Manifestations are usually mild and unlikely to require treatment. PMID:25663038

Examination of Physiological Function and Biochemical Disorders in a Rat Model of Prolonged Asphyxia-Induced Cardiac Arrest followed by Cardio Pulmonary Bypass Resuscitation

PubMed Central

Kim, Junhwan; Yin, Tai; Yin, Ming; Zhang, Wei; Shinozaki, Koichiro; Selak, Mary A.; Pappan, Kirk L.; Lampe, Joshua W.; Becker, Lance B.

2014-01-01

Background Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. Method A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. Results After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. Conclusion The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage. PMID:25383962

Examination of physiological function and biochemical disorders in a rat model of prolonged asphyxia-induced cardiac arrest followed by cardio pulmonary bypass resuscitation.

PubMed

Kim, Junhwan; Yin, Tai; Yin, Ming; Zhang, Wei; Shinozaki, Koichiro; Selak, Mary A; Pappan, Kirk L; Lampe, Joshua W; Becker, Lance B

2014-01-01

Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.

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

PubMed

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

2015-06-15

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

Cardiovascular progenitor-derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure.

PubMed

Kervadec, Anaïs; Bellamy, Valérie; El Harane, Nadia; Arakélian, Lousineh; Vanneaux, Valérie; Cacciapuoti, Isabelle; Nemetalla, Hany; Périer, Marie-Cécile; Toeg, Hadi D; Richart, Adèle; Lemitre, Mathilde; Yin, Min; Loyer, Xavier; Larghero, Jérôme; Hagège, Albert; Ruel, Marc; Boulanger, Chantal M; Silvestre, Jean-Sébastien; Menasché, Philippe; Renault, Nisa K E

2016-06-01

Cell-based therapies are being explored as a therapeutic option for patients with chronic heart failure following myocardial infarction. Extracellular vesicles (EV), including exosomes and microparticles, secreted by transplanted cells may orchestrate their paracrine therapeutic effects. We assessed whether post-infarction administration of EV released by human embryonic stem cell-derived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. Mice underwent surgical occlusion of their left coronary arteries. After 2-3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg-treated and EV-treated hearts were clustered into functionally relevant pathways. At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (-4.20 ± 0.96 µl or -7.5%, p = 0.0007) and end-diastolic (-4.48 ± 1.47 µl or -4.4%, p = 0.009) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell-derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg-derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg-treated animals and EV-treated animals compared with alpha-MEM-treated control animals. In the hESC-Pg-treated and EV-treated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. In this post-infarct heart failure model, either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. Although the mechanisms by which EV improve cardiac function remain to be determined, these results support the idea that a paracrine mechanism is sufficient to effect functional recovery in cell-based therapies for post-infarction-related chronic heart failure. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Evaluation of cardiac function in active and hibernating grizzly bears.

PubMed

Nelson, O Lynne; McEwen, Margaret-Mary; Robbins, Charles T; Felicetti, Laura; Christensen, William F

2003-10-15

To evaluate cardiac function parameters in a group of active and hibernating grizzly bears. Prospective study. 6 subadult grizzly bears. Indirect blood pressure, a 12-lead ECG, and a routine echocardiogram were obtained in each bear during the summer active phase and during hibernation. All measurements of myocardial contractility were significantly lower in all bears during hibernation, compared with the active period. Mean rate of circumferential left ventricular shortening, percentage fractional shortening, and percentage left ventricular ejection fraction were significantly lower in bears during hibernation, compared with the active period. Certain indices of diastolic function appeared to indicate enhanced ventricular compliance during the hibernation period. Mean mitral inflow ratio and isovolumic relaxation time were greater during hibernation. Heart rate was significantly lower for hibernating bears, and mean cardiac index was lower but not significantly different from cardiac index during the active phase. Contrary to results obtained in hibernating rodent species, cardiac index was not significantly correlated with heart rate. Cardiac function parameters in hibernating bears are opposite to the chronic bradycardic effects detected in nonhibernating species, likely because of intrinsic cardiac muscle adaptations during hibernation. Understanding mechanisms and responses of the myocardium during hibernation could yield insight into mechanisms of cardiac function regulation in various disease states in nonhibernating species.

Effects of Obesity on Cardiovascular Hemodynamics, Cardiac Morphology, and Ventricular Function.

PubMed

Alpert, Martin A; Omran, Jad; Bostick, Brian P

2016-12-01

Obesity produces a variety of hemodynamic alterations that may cause changes in cardiac morphology which predispose to left and right ventricular dysfunction. Various neurohormonal and metabolic alterations commonly associated with obesity may contribute to these abnormalities of cardiac structure and function. These changes in cardiovascular hemodynamics, cardiac morphology, and ventricular function may, in severely obese patients, predispose to heart failure, even in the absence of other forms of heart disease (obesity cardiomyopathy). In normotensive obese patients, cardiac involvement is commonly characterized by elevated cardiac output, low peripheral vascular resistance, and increased left ventricular (LV) end-diastolic pressure. Sleep-disordered breathing may lead to pulmonary arterial hypertension and, in association with left heart failure, may contribute to elevation of right heart pressures. These alterations, in association with various neurohormonal and metabolic abnormalities, may produce LV hypertrophy; impaired LV diastolic function; and less commonly, LV systolic dysfunction. Many of these alterations are reversible with substantial voluntary weight loss.

Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing cardiac effects of long-term enzyme replacement therapy.

PubMed

Messalli, G; Imbriaco, M; Avitabile, G; Russo, R; Iodice, D; Spinelli, L; Dellegrottaglie, S; Cademartiri, F; Salvatore, M; Pisani, A

2012-02-01

Anderson-Fabry disease is a multisystemic disorder of lipid metabolism secondary to X-chromosome alterations and is frequently associated with cardiac manifestations such as left ventricular (LV) hypertrophy, gradually leading to an alteration in cardiac performance. The purpose of this study was to monitor, using magnetic resonance imaging (MRI), any changes produced by enzyme replacement therapy with agalsidase beta at the cardiac level in patients with Anderson-Fabry disease. Sixteen (ten men, six women) patients with genetically confirmed Anderson-Fabry disease underwent cardiac MRI before starting enzyme replacement therapy (baseline study) and after 48 months of treatment with agalsidase beta at the dose of 1 mg/kg (follow-up study). After 48 months of treatment, a significant reduction in LV mass and wall thickness was observed: 187±59 g vs. 149±44 g, and 16±3 mm vs. 13±3 mm, respectively. A significant reduction in T2 relaxation time was noted at the level of the interventricular septum (81±3 ms vs. 67±7 ms), at the apical level (80±8 ms vs. 63±6 ms) and at the level of the lateral wall (82±8 ms vs. 63±10 ms) (p<0.05). No significant variation was observed in ejection fraction between the two studies (65±3% vs. 64±2%; p>0.05) (mean bias 1.0); however, an improvement was noted in the New York Heart Association (NYHA) class of the majority of patients (12/16) (p<0.05). In patients with Anderson-Fabry disease undergoing enzyme replacement therapy with agalsidase beta, MRI documented a significant reduction in myocardial T2 relaxation time, a significant decrease in maximal myocardial thickness and in total LV mass. MRI did not reveal significant improvements in LV global systolic function; however, improvement in NYHA functional class was noted, consistent with improved diastolic function.

Phenotyping Cardiac Arrest: Bench and Bedside Characterization of Brain and Heart Injury Based on Etiology.

PubMed

Uray, Thomas; Lamade, Andrew; Elmer, Jonathan; Drabek, Tomas; Stezoski, Jason P; Missé, Amalea; Janesko-Feldman, Keri; Garman, Robert H; Chen, Niel; Kochanek, Patrick M; Dezfulian, Cameron; Callaway, Clifton W; Doshi, Ankur A; Frisch, Adam; Guyette, Francis X; Reynolds, Josh C; Rittenberger, Jon C

2018-06-01

Cardiac arrest etiology may be an important source of between-patient heterogeneity, but the impact of etiology on organ injury is unknown. We tested the hypothesis that asphyxial cardiac arrest results in greater neurologic injury than cardiac etiology cardiac arrest (ventricular fibrillation cardiac arrest), whereas ventricular fibrillation cardiac arrest results in greater cardiovascular dysfunction after return of spontaneous circulation. Prospective observational human and randomized animal study. University laboratory and ICUs. Five-hundred forty-three cardiac arrest patients admitted to ICU. Seventy-five male Sprague-Dawley rats. We examined neurologic and cardiovascular injury in Isoflurane-anesthetized rat cardiac arrest models matched by ischemic time. Hemodynamic and neurologic outcomes were assessed after 5 minutes no flow asphyxial cardiac arrest or ventricular fibrillation cardiac arrest. Comparison was made to injury patterns observed after human asphyxial cardiac arrest or ventricular fibrillation cardiac arrest. In rats, cardiac output (20 ± 10 vs 45 ± 9 mL/min) and pH were lower and lactate higher (9.5 ± 1.0 vs 6.4 ± 1.3 mmol/L) after return of spontaneous circulation from ventricular fibrillation cardiac arrest versus asphyxial cardiac arrest (all p < 0.01). Asphyxial cardiac arrest resulted in greater early neurologic deficits, 7-day neuronal loss, and reduced freezing time (memory) after conditioned fear (all p < 0.05). Brain antioxidant reserves were more depleted following asphyxial cardiac arrest. In adjusted analyses, human ventricular fibrillation cardiac arrest was associated with greater cardiovascular injury based on peak troponin (7.8 ng/mL [0.8-57 ng/mL] vs 0.3 ng/mL [0.0-1.5 ng/mL]) and ejection fraction by echocardiography (20% vs 55%; all p < 0.0001), whereas asphyxial cardiac arrest was associated with worse early neurologic injury and poor functional outcome at hospital discharge (n = 46 [18%] vs 102 [44%]; p < 0.0001). Most ventricular fibrillation cardiac arrest deaths (54%) were the result of cardiovascular instability, whereas most asphyxial cardiac arrest deaths (75%) resulted from neurologic injury (p < 0.0001). In transcending rat and human studies, we find a consistent phenotype of heart and brain injury after cardiac arrest based on etiology: ventricular fibrillation cardiac arrest produces worse cardiovascular dysfunction, whereas asphyxial cardiac arrest produces worsened neurologic injury associated with greater oxidative stress.

Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

PubMed

Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

2004-01-01

Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: an observational study.

PubMed

Amant, Frédéric; Van Calsteren, Kristel; Halaska, Michael J; Gziri, Mina Mhallem; Hui, Wei; Lagae, Lieven; Willemsen, Michèl A; Kapusta, Livia; Van Calster, Ben; Wouters, Heidi; Heyns, Liesbeth; Han, Sileny N; Tomek, Viktor; Mertens, Luc; Ottevanger, Petronella B

2012-03-01

Chemotherapy for the treatment of maternal cancers during pregnancy has become more acceptable in the past decade; however, the effect of prenatal exposure to chemotherapy on cardiac and neurodevelopmental outcomes of the offspring is still uncertain. We aimed to record the general health, cardiac function, and neurodevelopmental outcomes of children who were prenatally exposed to chemotherapy. We did an interim analysis of a multicentre observational cohort study assessing children who were prenatally exposed to maternal cancer staging and treatment, including chemotherapy. We assessed children at birth, at age 18 months, and at age 5-6, 8-9, 11-12, 14-15, or 18 years. We did clinical neurological examinations, tests of the general level of cognitive functioning (Bayley or intelligence quotient [IQ] test), electrocardiography and echocardiography, and administered a questionnaire on general health and development. From age 5 years, we also did audiometry, the Auditory Verbal Learning Test, and subtasks of the Children's Memory Scale, and the Test of Everyday Attention for Children, and we also completed the Child Behavior Checklist. This study is registered with ClinicalTrials.gov, number NCT00330447. 236 cycles of chemotherapy were administered in 68 pregnancies. We assessed 70 children, born at a median gestational age of 35·7 weeks (range 28·3-41·0; IQR 3·3; 47 women at <37 weeks), with a median follow-up period of 22·3 months (range 16·8-211·6; IQR 54·9). Although neurocognitive outcomes were within normal ranges, cognitive development scores were lower for children who were born preterm than for those born at full term. When controlling for age, sex, and country, the score for IQ increased by an average 11·6 points (95% CI 6·0-17·1) for each additional month of gestation (p<0·0001). Our measurements of the children's behaviour, general health, hearing, and growth corresponded with those of the general population. Cardiac dimensions and functions were within normal ranges. We identified a severe neurodevelopmental delay in both members of one twin pregnancy. Fetal exposure to chemotherapy was not associated with increased CNS, cardiac or auditory morbidity, or with impairments to general health and growth compared with the general population. However, subtle changes in cardiac and neurocognitive measurements emphasise the need for longer follow-up. Prematurity was common and was associated with impaired cognitive development. Therefore, iatrogenic preterm delivery should be avoided when possible. Research Foundation-Flanders; Research Fund-K U Leuven; Agency for Innovation by Science and Technology; Stichting tegen Kanker; Clinical Research Fund-University Hospitals Leuven; and Belgian Cancer Plan, Ministery of Health. Copyright © 2012 Elsevier Ltd. All rights reserved.

Soluble epoxide hydrolase inhibition does not prevent cardiac remodeling and dysfunction after aortic constriction in rats and mice.

PubMed

Morgan, Lisa A; Olzinski, Alan R; Upson, John J; Zhao, Shufang; Wang, Tao; Eisennagel, Stephen H; Hoang, Bao; Tunstead, James R; Marino, Joseph P; Willette, Robert N; Jucker, Beat M; Behm, David J

2013-04-01

Epoxyeicosatrienoic acids, substrates for soluble epoxide hydrolase (sEH), exhibit vasodilatory and antihypertrophic activities. Inhibitors of sEH might therefore hold promise as heart failure therapeutics. We examined the ability of sEH inhibitors GSK2188931 and GSK2256294 to modulate cardiac hypertrophy, fibrosis, and function after transverse aortic constriction (TAC) in rats and mice. GSK2188931 administration was initiated in rats 1 day before TAC, whereas GSK2256294 treatment was initiated in mice 2 weeks after TAC. Four weeks later, cardiovascular function was assessed, plasma was collected for drug and sEH biomarker concentrations, and left ventricle was isolated for messenger RNA and histological analyses. In rats, although GSK2188931 prevented TAC-mediated increases in certain genes associated with hypertrophy and fibrosis (α-skeletal actin and connective tissue growth factor), the compound failed to attenuate TAC-induced increases in left ventricle mass, posterior wall thickness, end-diastolic volume and pressure, and perivascular fibrosis. Similarly, in mice, GSK2256294 did not reverse cardiac remodeling or systolic dysfunction induced by TAC. Both compounds increased the sEH substrate/product (leukotoxin/leukotoxin diol) ratio, indicating sEH inhibition. In summary, sEH inhibition does not prevent cardiac remodeling or dysfunction after TAC. Thus, targeting sEH seems to be insufficient for reducing pressure overload hypertrophy.

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.

PubMed

Palpant, Nathan J; D'Alecy, Louis G; Metzger, Joseph M

2009-05-01

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

PubMed

Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

2014-11-01

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Decreased cardiac vagal control in drug-naive patients with panic disorder: a case-control study in Taiwan.

PubMed

Chang, Hsin-An; Chang, Chuan-Chia; Tzeng, Nian-Sheng; Kuo, Terry B J; Lu, Ru-Band; Huang, San-Yuan

2013-06-01

Cardiac autonomic dysregulation has been proposed in panic disorder (PD), but the results are mixed. Analyses with larger sample sizes and better methodology are needed. Forty-eight drug-naïve individuals with PD and 202 healthy volunteers were recruited for a case-control analysis. We used the Hamilton Anxiety Rating Scale and the Beck Anxiety Inventory to assess anxiety severity. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The obtained results were evaluated in association with personality traits assessed by the Tridimensional Personality Questionnaire. Patients exhibited reduced mean RR interval (816.94 ± 135.92 versus 873.47 ± 143.36 ms, P = 0.014) and HRV levels (Var 6.37 ± 1.32 versus 7.38 ± 0.95, LF 4.90 ± 1.63 versus5.82 ± 1.11 and HF 4.57 ± 1.53 versus 5.62 ± 1.24 [ln(ms2)], all P < 0.001) as compared to controls, which mainly suggested a reduction in cardiac vagal control in PD. The anxiety severity was negatively correlated with HRV levels (r = -0.29 for Var, r = -0.22 for LF and r = -0.28 for HF, all P < 0.001). The harm avoidance score (which has been suggested to be associated with serotonergic activity) was associated with decreased HRV levels (r = -0.22 for Var, P < 0.01, r = -0.14 for LF, P < 0.05 and r = -0.17 for HF, P < 0.01). This study demonstrates that PD is associated with cardiac autonomic dysregulation, highlighting the importance of assessing HRV in PD patients. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

Early detection of cardiac involvement in sarcoidosis with 2-dimensional speckle-tracking echocardiography.

PubMed

Schouver, Elie-Dan; Moceri, Pamela; Doyen, Denis; Tieulie, Nathalie; Queyrel, Viviane; Baudouy, Delphine; Cerboni, Pierre; Gibelin, Pierre; Leroy, Sylvie; Fuzibet, Jean-Gabriel; Ferrari, Emile

2017-01-15

Cardiac sarcoidosis (CS) is associated with high morbidity and sudden death. The absence of specific symptoms and lack of diagnostic gold standard technique is challenging. New imaging methods could improve the diagnosis of CS. The aim of our study was to assess the role of left ventricular (LV) longitudinal and circumferential strain as estimated by 2D speckle-tracking imaging in patients with diagnosed sarcoidosis without cardiac involvement according to the current guidelines. We investigated the prevalence of LV strain impairment in this population and assessed its relationship with clinical outcomes, composite of mortality, heart failure, arrhythmia and/or secondarily development of CS and cardiac device implantation. We performed a prospective case-control longitudinal study including 35 patients with diagnosed sarcoidosis and normal cardiac function as assessed by standard transthoracic echocardiography and 35 healthy age- and gender-matched controls. All patients underwent a comprehensive echocardiographic study. Mean age of patients was 47.9±14.8years old (22 women). Compared with controls, global LV longitudinal strain (LV GLS) was reduced in sarcoidosis patients: (-17.2±3.1 vs -21.3±1.5%, p<0.0001). Circumferential LV strain was preserved in patients compared to controls (-19.9±-4.3% vs -21.3±1.5%, p=0.12). Impaired LV GLS was significantly associated with clinical outcomes (HR 1.56; [1.16-2.11], p<0.01) on univariate analysis. Speckle-tracking echocardiography revealed decreased longitudinal LV strain in sarcoidosis patients that was associated with outcomes. LV GLS may represent an early marker of myocardial involvement in sarcoidosis patients that needs to be studied further. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Modern nuclear cardiac imaging in diagnosis and clinical management of patients with left ventricular dysfunction.

PubMed

Abidov, A; Hachamovitch, R; Berman, D S

2004-12-01

Congestive heart failure (CHF) has become a large social burden in modern Western society, with very high morbidity and mortality and extremely large financial costs. The largest cause of CHF is coronary heart disease, with ventricular dysfunction that may or may not be reversible by revascularization. Thus, evaluation of the viable myocardial tissue in patients with ischemic left ventricular (LV) dysfunction has important clinical and therapeutic implications. Furthermore, since patients with ventricular dysfunction are at higher operative risk, cardiologists and cardiac surgeons are commonly faced with issues regarding the balance between the potential risk vs benefit of revascularization procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and positron emission tomography (PET)] provide objective information that augments standard clinical and angiographic assessments of patients with ventricular dysfunction with respect to diagnosis (etiology), prognosis, and potential benefit from intervention. Development of the technology and methodology of gated MPS, now the routine method for MPS, allows assessment of the extent and severity of inducible ischemia as well as hypoperfused but viable myocardium, and also provides measurements of LV ejection fraction, regional wall motion, LV volume measurements, diastolic function and LV geometry. With PET, myocardial metabolism and blood flow reserve can be added to the measurements provided by nuclear cardiology procedures. This paper provides insight into the current evidence regarding settings in which nuclear cardiac imaging procedures are helpful in assessment of patients in the setting of coronary artery disease with severe LV dysfunction. A risk-benefit approach to MPS results is proposed, with principal focus on identifying patients at risk for major cardiac events who may benefit from myocardial revascularization.

Translational science approach for assessment of cardiovascular effects and proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron.

PubMed

Korstanje, Cees; Suzuki, Masanori; Yuno, Koichiro; Sato, Shuichi; Ukai, Masashi; Schneidkraut, Marlowe J; Yan, Gan X

2017-09-01

Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron. Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (I Kr , I Ks , I to , I Na , and I Ca,L ), on QT-interval, subendocardial APD 90 , T peak-end interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QT c ) in conscious dogs. In conscious dogs, mirabegron (0.01-10mg/kg, p.o.) dose-dependently increased HR, reduced SBP but DBP was unchanged. Propranolol blocked the decrease in SBP and attenuated HR increase at 100mg/kg mirabegron. Mirabegron, at 30, 60, or 100mg/kg, p.o., had no significant effect on the QT c interval. In paced dog ventricular wedge, neither mirabegron nor metabolites M5, M11, M12, M14, and M16 prolonged QT, altered transmural dispersion of repolarization, induced premature ventricular contractions, or induced ventricular tachycardia. Mirabegron nor its metabolites inhibited I Kr , I Ks , I to I Na , or I Ca,L at clinically relevant concentrations. Up to exposure levels well exceeding human clinical exposure no discernible effects on ion channel conductance or on arrhythmogenic parameters in ventricular wedge resulted for mirabegron, or its main metabolites, confirming human cardiac safety findings. In vivo, dose-related increases in HR with effects markedly higher than seen clinically, was mediated in part by cross-activation of beta-1 adrenoceptors. This non-clinical cardiac safety test program therefore proved predictive for human cardiac safety for mirabegron. Copyright © 2017. Published by Elsevier Inc.

Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat.

PubMed

Bakrania, B; Du Toit, E F; Ashton, K J; Wagner, K-H; Headrick, J P; Bulmer, A C

2017-08-01

Bilirubin is associated with reduced risk of cardiovascular disease, as evidenced in conditions of mild hyperbilirubinaemia (Gilbert's Syndrome). Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life-long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease. Hyperbilirubinaemic rats and littermate controls underwent echocardiography at 3, 6 and 12 months of age, with hearts subsequently assessed for resistance to 30 min of ischaemia. Heart tissue was then collected for assessment of bilirubin content. No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. Additionally, duration of ventricular ejection increased progressively, indicating a negative inotropic effect of bilirubin in vivo. Ex vivo analysis of baseline function revealed reduced left ventricular pressure development (LVDP) and contractility in hyperbilirubinaemic rats. Furthermore, stress resistance was improved in Gunn hearts: post-ischaemic recoveries of LVDP (76 ± 22% vs. 29 ± 17% Control, P < 0.01) and coronary flow (96 ± 9% vs. 86 ± 16% Control, P < 0.01) were improved in Gunn hearts, accompanied by reduced infarct area (21 ± 5% vs. 47 ± 15% Control, P < 0.01), and ventricular malondialdehyde and protein carbonyl content. Expression of myocardial nitric oxide-regulating genes including Nos1 and Noa1 were not significantly different. These data reveal life-long hyperbilirubinaemia induces age-dependent hypocontractility in male Gunn rats, and improved stress resistance. In addition, bilirubin exerts sex-independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Neighborhood characteristics, bystander automated external defibrillator use, and patient outcomes in public out-of-hospital cardiac arrest.

PubMed

Andersen, Lars W; Holmberg, Mathias J; Granfeldt, Asger; Løfgren, Bo; Vellano, Kimberly; McNally, Bryan F; Siegerink, Bob; Kurth, Tobias; Donnino, Michael W

2018-05-01

Automated external defibrillators (AEDs) can be used by bystanders to provide rapid defibrillation for patients with out-of-hospital cardiac arrest (OHCA). Whether neighborhood characteristics are associated with AED use is unknown. Furthermore, the association between AED use and outcomes has not been well characterized for all (i.e. shockable and non-shockable) public OHCAs. We included public, non-911-responder witnessed OHCAs registered in the Cardiac Arrest Registry to Enhance Survival (CARES) between 2013 and 2016. The primary patient outcome was survival to hospital discharge with a favorable functional outcome. We first assessed the association between neighborhood characteristics and bystander AED use using logistic regression and then assessed the association between bystander AED use and patient outcomes in a propensity score matched cohort. 25,182 OHCAs were included. Several neighborhood characteristics, including the proportion of people living alone, the proportion of white people, and the proportion with a high-school degree or higher, were associated with bystander AED use. 5132 OHCAs were included in the propensity score-matched cohort. Bystander AED use was associated with an increased risk of a favorable functional outcome (35% vs. 25%, risk difference: 9.7% [95% confidence interval: 7.2%, 12.2%], risk ratio: 1.38 [95% confidence interval: 1.27, 1.50]). This was driven by increased favorable functional outcomes with AED use in patients with shockable rhythms (58% vs. 39%) but not in patients with non-shockable rhythms (10% vs. 10%). Specific neighborhood characteristics were associated with bystander AED use in OHCA. Bystander AED use was associated with an increase in favorable functional outcome. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of aortic and carotid baroreflex stimulus-response characteristics in humans

NASA Technical Reports Server (NTRS)

Smith, S. A.; Querry, R. G.; Fadel, P. J.; Weiss, M. W.; Olivencia-Yurvati, A.; Shi, X.; Raven, P. B.

2001-01-01

In order to characterize the stimulus-response relationships of the arterial, aortic, and carotid baroreflexes in mediating cardiac chronotropic function, we measured heart rate (HR) responses elicited by acute changes in mean arterial pressure (MAP) and carotid sinus pressure (CSP) in 11 healthy individuals. Arterial (aortic + carotid) baroreflex control of HR was quantified using ramped changes in MAP induced by bolus injection of phenylephrine (PE) and sodium nitroprusside (SN). To assess aortic-cardiac responses, neck pressure (NP) and suction (NS) were applied during PE and SN administration, respectively, to counter alterations in CSP thereby isolating the aortic baroreflex. Graded levels of NP and NS were delivered to the carotid sinus using a customized neck collar device to assess the carotid-cardiac baroreflex, independent of drug infusion. The operating characteristics of each reflex were determined from the logistic function of the elicited HR response to the induced change in MAP. The arterial pressures at which the threshold was located on the stimulus-response curves determined for the arterial, aortic and carotid baroreflexes were not significantly different (72+/-4, 67+/-3, and 72+/-4 mm Hg, respectively, P > 0.05). Similarly, the MAP at which the saturation of the reflex responses were elicited did not differ among the baroreflex arcs examined (98+/-3, 99+/-2, and 102+/-3 mm Hg, respectively). These data suggest that the baroreceptor populations studied operate over the same range of arterial pressures. This finding indicates each baroreflex functions as both an important anti-hypotensive and anti-hypertensive mechanism. In addition, this investigation describes a model of aortic baroreflex function in normal healthy humans, which may prove useful in identifying the origin of baroreflex dysfunction in disease- and training-induced conditions.

Atherosclerosis and cardiac function assessment in low-density lipoprotein receptor-deficient mice undergoing body weight cycling.

PubMed

McMillen, T S; Minami, E; Leboeuf, R C

2013-06-24

Obesity has become an epidemic in many countries and is supporting a billion dollar industry involved in promoting weight loss through diet, exercise and surgical procedures. Because of difficulties in maintaining body weight reduction, a pattern of weight cycling often occurs (so called 'yo-yo' dieting) that may result in deleterious outcomes to health. There is controversy about cardiovascular benefits of yo-yo dieting, and an animal model is needed to better understand the contributions of major diet and body weight changes on heart and vascular functions. Our purpose is to determine the effects of weight cycling on cardiac function and atherosclerosis development in a mouse model. We used low-density lipoprotein receptor-deficient mice due to their sensitivity to metabolic syndrome and cardiovascular diseases when fed high-fat diets. Alternating ad libitum feeding of high-fat and low-fat (rodent chow) diets was used to instigate weight cycling during a 29-week period. Glucose tolerance and insulin sensitivity tests were done at 22 and 24 weeks, echocardiograms at 25 weeks and atherosclerosis and plasma lipoproteins assessed at 29 weeks. Mice subjected to weight cycling showed improvements in glucose homeostasis during the weight loss cycle. Weight-cycled mice showed a reduction in the severity of atherosclerosis as compared with high-fat diet-fed mice. However, atherosclerosis still persisted in weight-cycled mice as compared with mice fed rodent chow. Cardiac function was impaired in weight-cycled mice and matched with that of mice fed only the high-fat diet. This model provides an initial structure in which to begin detailed studies of diet, calorie restriction and surgical modifications on energy balance and metabolic diseases. This model also shows differential effects of yo-yo dieting on metabolic syndrome and cardiovascular diseases.

Prognostic value of echocardiographic indices of left atrial morphology and function in dogs with myxomatous mitral valve disease

PubMed Central

Romito, Giovanni; Guglielmini, Carlo; Diana, Alessia; Pelle, Nazzareno G.; Contiero, Barbara; Cipone, Mario

2018-01-01

Background The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. Objectives To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). Animals One‐hundred and fifteen dogs of different breeds with MMVD. Methods Prospective cohort study. Conventional morphologic and echo‐Doppler variables, LA areas and volumes, and STE‐based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac‐related death. Results Most of the tested variables, including all LA STE‐derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76‐11.24; P < .001) and LAVmax (HR, 2.32; CI, 1.10‐4.89; P = .024) remained statistically significant in the multivariable analysis. Conclusions and Clinical Importance The assessment of LA dimension and function provides useful prognostic information in dogs with MMVD. Considering all the LA variables, LAVmax appears the strongest predictor of cardiac death, being superior to LA/Ao and STE‐derived variables. PMID:29572938

Detection of Early Right Ventricular Dysfunction in Young Patients With Thalassemia Major Using Tissue Doppler Imaging

PubMed Central

Bornaun, Helen; Dedeoglu, Reyhan; Oztarhan, Kazim; Dedeoglu, Savas; Erfidan, Erkan; Gundogdu, Muge; Aydogan, Gonul; Cengiz, Dicle

2016-01-01

Background Myocardial iron overload is the most common cause of mortality in patients with thalassemia major (TM), also known as beta-thalassemia. T2* cardiovascular magnetic resonance imaging (MRI) is the best way of monitoring cardiac iron, and new echocardiographic techniques can be used to assess cardiac function. Objectives The aim of this study was to assess the systolic and diastolic right ventricular (RV) function of patients with TM using tissue Doppler imaging (TDI) and to determine whether this echocardiographic technique is an adequate diagnostic tool for the screening and detection of subclinical cardiac dysfunction. Patients and Methods Eighty-four patients with TM were evaluated by conventional echocardiography and pulse-wave TDI. The data of the TM group (Group 1) were compared with that of 85 age- and sex-matched healthy controls (Group 2). Cardiovascular T2* MRI examinations were performed in 49 of the 85 patients. Results The patients with TM had significantly lower values for weight, height, body mass index, systolic arterial pressure, deceleration time, E’/A’, and ejection time (ET) than the controls. Group 1 also had significantly higher values for peak early diastolic velocity (E) over peak late diastolic velocity (A), peak early diastolic velocity of TDI (E’), peak late diastolic velocity of TDI (A’), E/E’, isovolumetric relaxation time, isovolumetric contraction time, and RV magnetic perfusion imaging (MPI) than Group 2. Conclusions RV diastolic dysfunction occurs before systolic deterioration in patients with TM and cannot be screened with conventional echocardiographic techniques. In routine practice, TDI measurements, MPI (for global function) and the E/E’ parameter (for diastolic function) can be used to screen and detect early RV dysfunction. PMID:27617076

Automatic right ventricle (RV) segmentation by propagating a basal spatio-temporal characterization

NASA Astrophysics Data System (ADS)

Atehortúa, Angélica; Zuluaga, María. A.; Martínez, Fabio; Romero, Eduardo

2015-12-01

An accurate right ventricular (RV) function quantification is important to support the evaluation, diagnosis and prognosis of several cardiac pathologies and to complement the left ventricular function assessment. However, expert RV delineation is a time consuming task with high inter-and-intra observer variability. In this paper we present an automatic segmentation method of the RV in MR-cardiac sequences. Unlike atlas or multi-atlas methods, this approach estimates the RV using exclusively information from the sequence itself. For so doing, a spatio-temporal analysis segments the heart at the basal slice, segmentation that is then propagated to the apex by using a non-rigid-registration strategy. The proposed approach achieves an average Dice Score of 0:79 evaluated with a set of 48 patients.

C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

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

Olson, Aaron; Ledee, Dolena; Iwamoto, Kate

The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids,more » acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained compensated function could provide useful information for developing metabolic therapies to treat heart failure. The molecular signaling for this metabolic change may occur through O-GlcNAcylation.« less

[Cardiac failure in endocrine diseases].

PubMed

Hashizume, K

1993-05-01

Several endocrine diseases show the symptoms of cardiac failure. Among them, patients with acromegaly show a specific cardiomyopathy which results in a severe left-sided cardiac failure. Hypoparathyroidism also induces cardiac failure, which is resulted from hypocalcemia and low levels of serum parathyroid hormone. In the cases of hypothyroidism, the patients with myxedemal coma show a severe cardiac failure, which is characterized by disturbance of central nervous system, renal function, and cardiac function. In the patients with thyroid crisis (storm), the cardiac failure comes from the great reduction of cardiac output with dehydration. The reduction of circulation volume, observed in the patients with pheochromocytoma easily induces cardiac failure (shock) just after the removal of adrenal tumor. In patients with malignant carcinoid syndrome, right-sided ventricular failure which may be occurred through the actions of biogenic amines is observed.

Cardiac Fibroblast: The Renaissance Cell

PubMed Central

Souders, Colby A.; Bowers, Stephanie L.K.; Baudino, Troy A.

2012-01-01

The permanent cellular constituents of the heart include cardiac fibroblasts, myocytes, endothelial cells and vascular smooth muscle cells. Previous studies have demonstrated that there are undulating changes in cardiac cell populations during embryonic development, through neonatal development and into the adult. Transient cell populations include lymphocytes, mast cells and macrophages, which can interact with these permanent cell types to affect cardiac function. It has also been observed that there are marked differences in the makeup of the cardiac cell populations depending on the species, which may be important when examining myocardial remodeling. Current dogma states that the fibroblast makes up the largest cell population of the heart; however, this appears to vary for different species, especially mice. Cardiac fibroblasts play a critical role in maintaining normal cardiac function, as well as in cardiac remodeling during pathological conditions such as myocardial infarct and hypertension. These cells have numerous functions, including synthesis and deposition of extracellular matrix, cell-cell communication with myocytes, cell-cell signaling with other fibroblasts, as well as with endothelial cells. These contacts affect the electrophysiological properties, secretion of growth factors and cytokines, as well as potentiating blood vessel formation. While a plethora of information is known about several of these processes, relatively little is understood about fibroblasts and their role in angiogenesis during development or cardiac remodeling. In this review we provide insight into the various properties of cardiac fibroblasts that helps illustrate their importance in maintaining proper cardiac function, as well as their critical role in the remodeling heart. PMID:19959782

Assessment of cardiac structure and function in patients without and with peripheral oedema during rosiglitazone treatment.

PubMed

Narang, Nikhil; Armstead, Sumiko I; Stream, Amanda; Abdullah, Shuaib M; See, Raphael; Snell, Peter G; McGavock, Jonathan; Ayers, Colby R; Gore, M Odette; Khera, Amit; de Lemos, James A; McGuire, Darren K

2011-04-01

Thiazolidinediones cause peripheral oedema, the aetiology of which remains poorly understood. In a sub-study of a 6-month trial comparing rosiglitazone (Rsg) versus placebo, we compared those with versus without oedema among the 74 subjects treated with Rsg with respect to peak oxygen consumption indexed to fat-free mass (VO(2peak-FFM) ), cardiac MRI and markers of plasma volume expansion. Almost half (49%) of the Rsg-treated patients developed oedema. Baseline VO(2peak-FFM) was not different between those with versus without oedema (25.8 versus 28.2 ml/kg/min; p = 0.22) and declined 5% in the oedema group (Δ -1.3 ml/min/kg; p = 0.005) with no change in those without oedema. Stroke volume increased in both groups (Δ 8.7 and 8.8 ml; p < 0.001 for each); end-diastolic volume increased only in those with oedema (+13.1 ml; p = 0.001). No other cardiac function changes were observed. In both groups, weight increased (3.6 and 2.2 kg) and haematocrit decreased (-3.2% and -2.1%; p < 0.001 for each). In those with oedema, albumin decreased (-0.2 g/dl) and brain natriuretic peptide increased (11.9 pg/ml; p < 0.03 for each). Oedema was associated with a small decline in VO(2peak FFM), no adverse effects on cardiac function, and changes in selected measures suggesting that volume expansion underpins Rsg oedema.

Complete cardiac regeneration in a mouse model of myocardial infarction.

PubMed

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

2012-12-01

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

TU-EF-304-04: A Heart Motion Model for Proton Scanned Beam Chest Radiotherapy

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

White, B; Kiely, J Blanco; Lin, L

Purpose: To model fast-moving heart surface motion as a function of cardiac-phase in order to compensate for the lack of cardiac-gating in evaluating accurate dose to coronary structures. Methods: Ten subjects were prospectively imaged with a breath-hold, cardiac-gated MRI protocol to determine heart surface motion. Radial and planar views of the heart were resampled into a 3-dimensional volume representing one heartbeat. A multi-resolution optical flow deformable image registration algorithm determined tissue displacement during the cardiac-cycle. The surface of the heart was modeled as a thin membrane comprised of voxels perpendicular to a pencil beam scanning (PBS) beam. The membrane’s out-of-planemore » spatial displacement was modeled as a harmonic function with Lame’s equations. Model accuracy was assessed with the root mean squared error (RMSE). The model was applied to a cohort of six chest wall irradiation patients with PBS plans generated on phase-sorted 4DCT. Respiratory motion was separated from the cardiac motion with a previously published technique. Volumetric dose painting was simulated and dose accumulated to validate plan robustness (target coverage variation accepted within 2%). Maximum and mean heart surface dose assessed the dosimetric impact of heart and coronary artery motion. Results: Average and maximum heart surface displacements were 2.54±0.35mm and 3.6mm from the end-diastole phase to the end-systole cardiac-phase respectively. An average RMSE of 0.11±0.04 showed the model to be accurate. Observed errors were greatest between the circumflex artery and mitral valve level of the heart anatomy. Heart surface displacements correspond to a 3.6±1.0% and 5.1±2.3% dosimetric impact on the maximum and mean heart surface DVH indicators respectively. Conclusion: Although heart surface motion parallel to beam’s direction was substantial, its maximum dosimetric impact was 5.1±2.3%. Since PBS delivers low doses to coronary structures relative to photon radiotherapy, it is unknown whether this variation would be clinically significant for late effects.« less

Research protocol for platelets in out-of-hospital cardiac arrest: an observational, case-controlled, feasibility study to assess coagulation and platelet function abnormalities with ROTEM following out-of-hospital cardiac arrest (PoHCAR).

PubMed

Skorko, Agnieszka; Thomas, Matthew; Mumford, Andrew; Johnson, Thomas; Griffiths, Elinor; Greenwood, Rosemary; Benger, Jonathan

2017-07-10

Out-of-hospital cardiac arrest (OHCA) has an annual incidence of approximately 60 000 in the UK. Less than 10% of those who receive resuscitation survive to hospital discharge. For OHCA of a presumed cardiac cause, the optimal antiplatelet therapy is currently unknown. Previous studies indicate that a procoagulopathic state exists postcardiac arrest which may contribute to the formation of thrombi and contribute to poor outcomes. However, the administration of antiplatelet therapies needs to be balanced against the increased risk of bleeding that these individuals face. This observational feasibility study will recruit 30 individuals who achieve return of spontaneous circulation post-OHCA, are admitted to a single tertiary centre over a 6-month period and meet Utstein cohort criteria (witnessed cardiac arrest, VF or pulseless VT and cardiac cause of arrest likely). Rotational thromboelastometry and platelet function assessment will be performed on hospital arrival, postemergency percutaneous coronary intervention (PCI) and 12 hours, 24 hours and 48 hours post-PCI. As a comparator, 30 individuals presenting to our institution with ST-segment elevation myocardial infarction and undergoing primary PCI will have the same blood sampling performed. Plasma samples will be retained and batch tested on completion of the study for levels of protein C, protein S, thrombin-antithrombin complex, thrombin, antithrombin, plasminogen activator inhibitor-1, plasmin-antiplasmin complex, d-dimer, platelet factor-4, P selectin, E selectin and prothrombin fragments 1 and 2. 30-day follow-up for complications will be undertaken. This study has been approved by the Wales REC 7Research Ethics Committee. The results will be submitted to peer-reviewed medical journals and suitable national and international meetings. Results will be locally disseminated via our patient and public interest group. Pre-results; ISRCTN34122839. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

FT011, a new anti-fibrotic drug, attenuates fibrosis and chronic heart failure in experimental diabetic cardiomyopathy.

PubMed

Zhang, Yuan; Edgley, Amanda J; Cox, Alison J; Powell, Andrew K; Wang, Bing; Kompa, Andrew R; Stapleton, David I; Zammit, Steven C; Williams, Spencer J; Krum, Henry; Gilbert, Richard E; Kelly, Darren J

2012-05-01

Cardiac remodelling in diabetes includes pathological accumulation of extracellular matrix and myocyte hypertrophy that contribute to heart dysfunction. Attenuation of remodelling represents a potential therapeutic target. We tested this hypothesis using a new anti-fibrotic drug, FT011 (Fibrotech Therapeutics Pty Ltd), on diabetic Ren-2 rats, a model which replicates many of the structural and functional manifestations of diabetic cardiomyopathy in humans. Homozygous Ren-2 rats were randomized to receive streptozotocin or vehicle then further randomized to FT011 (200 mg/kg/day) or vehicle treatment for 6 weeks. Prior to tissue collection, cardiac function was assessed via echocardiography and cardiac catheterization. Total collagen deposition and cardiomyocyte hypertrophy were assessed by picrosirius red and haematoxylin and eosin staining, respectively. Macrophage interstitial infiltration and type I and III collagen were quantitated by immunostaining. Without affecting blood pressure or hyperglycaemia, treatment of diabetic rats with FT011 significantly attenuated interstitial fibrosis (total collagen, 5.09 ±1.28 vs, 2.42 ±0.43%/area; type I collagen, 4.09 ±1.16 vs. 1.42 ±0.38%/area; type III collagen, 1.52 ±0.33 vs. 0.71 ±0.14 %/area; P < 0.05), cardiomyocyte hypertrophy (882 ±38 vs. 659 ±28 µm(2); P < 0.05), and interstitial macrophage influx (66 ±5.3 vs, 44 ±7.9 number/section; P < 0.05). Cardiac myopathic dilatation was normalized, as evidenced by reduced left ventricular inner diameter at diastole (0.642 ±0.016 vs. 0.577 ±0.024 cm), increased ejection fraction (75 ±1.1 vs. 83 ±1.2%) and preload recruitable stroke work relationship (44 ±6.7 vs. 77 ±6.3 slope-mmHg; P < 0.05), and reduced end-diastolic pressure-volume relationship (0.059 ±0.011 vs. 0.02 ±0.003 slope-mmHg/μL; P < 0.05). A direct anti-fibrotic agent, FT011, attenuates cardiac remodelling and dysfunction in experimental diabetic cardiomyopathy. This represents a novel therapy for the treatment of diabetic cardiomyopathy associated with cardiac fibrosis and hypertrophy.

ECG telemetry in conscious guinea pigs.

PubMed

Ruppert, Sabine; Vormberge, Thomas; Igl, Bernd-Wolfgang; Hoffmann, Michael

2016-01-01

During preclinical drug development, monitoring of the electrocardiogram (ECG) is an important part of cardiac safety assessment. To detect potential pro-arrhythmic liabilities of a drug candidate and for internal decision-making during early stage drug development an in vivo model in small animals with translatability to human cardiac function is required. Over the last years, modifications/improvements regarding animal housing, ECG electrode placement, and data evaluation have been introduced into an established model for ECG recordings using telemetry in conscious, freely moving guinea pigs. Pharmacological validation using selected reference compounds affecting different mechanisms relevant for cardiac electrophysiology (quinidine, flecainide, atenolol, dl-sotalol, dofetilide, nifedipine, moxifloxacin) was conducted and findings were compared with results obtained in telemetered Beagle dogs. Under standardized conditions, reliable ECG data with low variability allowing largely automated evaluation were obtained from the telemetered guinea pig model. The model is sensitive to compounds blocking cardiac sodium channels, hERG K(+) channels and calcium channels, and appears to be even more sensitive to β-blockers as observed in dogs at rest. QT interval correction according to Bazett and Sarma appears to be appropriate methods in conscious guinea pigs. Overall, the telemetered guinea pig is a suitable model for the conduct of early stage preclinical ECG assessment. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardio-oncology/onco-cardiology.

PubMed

Hong, Robert A; Iimura, Takeshi; Sumida, Kenneth N; Eager, Robert M

2010-12-01

An understanding of onco-cardiology or cardio-oncology is critical for the effective care of cancer patients. Virtually all antineoplastic agents are associated with cardiotoxicity, which can be divided into 5 categories: direct cytotoxic effects of chemotherapy and associated cardiac systolic dysfunction, cardiac ischemia, arrhythmias, pericarditis, and chemotherapy-induced repolarization abnormalities. Radiation therapy can also lead to coronary artery disease and fibrotic changes to the valves, pericardium, and myocardium. All patients being considered for chemotherapy, especially those who have prior cardiac history, should undergo detailed cardiovascular evaluation to optimize the treatment. Serial assessment of left ventricular systolic function and cardiac biomarkers might also be considered in selected patient populations. Cardiotoxic effects of chemotherapy might be decreased by the concurrent use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Antiplatelet or anticoagulation therapy might be considered in patients with a potential hypercoagulable state associated with chemotherapy or cancer. Open dialogue between both cardiologists and oncologists will be required for optimal patient care. Copyright © 2010 Wiley Periodicals, Inc.

Myocardial ischaemia and cardiac pain – a mysterious relationship

PubMed Central

Fisher, Mike

2013-01-01

Pain related to cardiac disease has been recognised for centuries. However, the precise mechanisms of angina pectoris remain bafflingly obscure. Conventional cardiological angina management concentrates on methods to improve oxygen delivery to cardiac myocytes as our understanding of cardiac muscle cells’ response to hypoxia increases. In common with other chronic visceral pain syndromes, little is understood about how pain signals are generated and propagated by visceral nerves. Improved imaging and other physiological assessments have demonstrated important central nervous system (CNS) responses to myocardial ischaemia, including activation of CNS areas known to be ‘key players’ in chronic pain syndromes. Patients with stable angina usually have an excellent prognosis, especially if left ventricular function is preserved. Educating patients about their condition, teaching simple techniques known to help chronic pain patients and introducing targeted pain treatments specific to angina can be extremely helpful adjuncts to conventional cardiological treatments and will often bring about significant improvements in quality of life. PMID:26516494

Associations between attention, affect and cardiac activity in a single yoga session for female cancer survivors: an enactive neurophenomenology-based approach.

PubMed

Mackenzie, Michael J; Carlson, Linda E; Paskevich, David M; Ekkekakis, Panteleimon; Wurz, Amanda J; Wytsma, Kathryn; Krenz, Katie A; McAuley, Edward; Culos-Reed, S Nicole

2014-07-01

Yoga practice is reported to lead to improvements in quality of life, psychological functioning, and symptom indices in cancer survivors. Importantly, meditative states experienced within yoga practice are correlated to neurophysiological systems that moderate both focus of attention and affective valence. The current study used a mixed methods approach based in neurophenomenology to investigate associations between attention, affect, and cardiac activity during a single yoga session for female cancer survivors. Yoga practice was associated with a linear increase in associative attention and positive affective valence, while shifts in cardiac activity were related to the intensity of each yoga sequence. Changes in attention and affect were predicted by concurrently assessed cardiac activity. Awareness of breathing, physical movement, and increased relaxation were reported by participants as potential mechanisms for yoga's salutary effects. While yoga practice shares commonalities with exercise and relaxation training, yoga may serve primarily as a promising meditative attention-affect regulation training methodology. Copyright © 2014 Elsevier Inc. All rights reserved.

Fast interactive real-time volume rendering of real-time three-dimensional echocardiography: an implementation for low-end computers

NASA Technical Reports Server (NTRS)

Saracino, G.; Greenberg, N. L.; Shiota, T.; Corsi, C.; Lamberti, C.; Thomas, J. D.

2002-01-01

Real-time three-dimensional echocardiography (RT3DE) is an innovative cardiac imaging modality. However, partly due to lack of user-friendly software, RT3DE has not been widely accepted as a clinical tool. The object of this study was to develop and implement a fast and interactive volume renderer of RT3DE datasets designed for a clinical environment where speed and simplicity are not secondary to accuracy. Thirty-six patients (20 regurgitation, 8 normal, 8 cardiomyopathy) were imaged using RT3DE. Using our newly developed software, all 3D data sets were rendered in real-time throughout the cardiac cycle and assessment of cardiac function and pathology was performed for each case. The real-time interactive volume visualization system is user friendly and instantly provides consistent and reliable 3D images without expensive workstations or dedicated hardware. We believe that this novel tool can be used clinically for dynamic visualization of cardiac anatomy.

Point-of-Care Ultrasonography to Assess Portal Vein Pulsatility and the Effect of Inhaled Milrinone and Epoprostenol in Severe Right Ventricular Failure: A Report of 2 Cases.

PubMed

Tremblay, Jan-Alexis; Beaubien-Souligny, William; Elmi-Sarabi, Mahsa; Desjardins, Georges; Denault, André Y

2017-10-15

This article describes 2 patients with severe acute right ventricular failure causing circulatory shock. Portal vein pulsatility assessed by bedside ultrasonography suggested clinically relevant venous congestion. Management included cardiac preload reduction and combined inhalation of milrinone and epoprostenol to reduce right ventricular afterload. Portal vein ultrasonography may be useful in assessing right ventricular function in the acutely ill patient.

Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

PubMed

Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

2015-10-01

Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling

PubMed Central

de Sá, Felipe Gonçalves dos Santos; Lima-Leopoldo, Ana Paula; Jacobsen, Bruno Barcellos; Ferron, Artur Junio Togneri; Estevam, Wagner Muller; Campos, Dijon Henrique Salomé; Castardeli, Edson; da Cunha, Márcia Regina Holanda; Cicogna, Antonio Carlos; Leopoldo, André Soares

2015-01-01

Background Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. Objective To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Methods Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. Results The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Conclusion Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling. PMID:26761369

Chamber dimensions and functional assessment with coronary computed tomographic angiography as compared to echocardiography using American Society of Echocardiography guidelines

PubMed Central

Rose, Michael; Rubal, Bernard; Hulten, Edward; Slim, Jennifer N; Steel, Kevin; Furgerson, James L; Villines, Todd C

2014-01-01

Background: The correlation between normal cardiac chamber linear dimensions measured during retrospective coronary computed tomographic angiography as compared to transthoracic echocardiography using the American Society of Echocardiography guidelines is not well established. Methods: We performed a review from January 2005 to July 2011 to identify subjects with retrospective electrocardiogram-gated coronary computed tomographic angiography scans for chest pain and transthoracic echocardiography with normal cardiac structures performed within 90 days. Dimensions were manually calculated in both imaging modalities in accordance with the American Society of Echocardiography published guidelines. Left ventricular ejection fraction was calculated on echocardiography manually using the Simpson’s formula and by coronary computed tomographic angiography using the end-systolic and end-diastolic volumes. Results: We reviewed 532 studies, rejected 412 and had 120 cases for review with a median time between studies of 7 days (interquartile range (IQR25,75) = 0–22 days) with no correlation between the measurements made by coronary computed tomographic angiography and transthoracic echocardiography using Bland–Altman analysis. We generated coronary computed tomographic angiography cardiac dimension reference ranges for both genders for our population. Conclusion: Our findings represent a step towards generating cardiac chamber dimensions’ reference ranges for coronary computed tomographic angiography as compared to transthoracic echocardiography in patients with normal cardiac morphology and function using the American Society of Echocardiography guideline measurements that are commonly used by cardiologists. PMID:26770706

Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

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

Kirby, R. Jason

2016-08-15

Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicitymore » library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data.« less

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

PubMed

AbouEzzeddine, Omar F; Haines, Phillip; Stevens, Susanna; Nativi-Nicolau, Jose; Felker, G Michael; Borlaug, Barry A; Chen, Horng H; Tracy, Russell P; Braunwald, Eugene; Redfield, Margaret M

2015-03-01

This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.

PubMed

Bondanelli, Marta; Bonadonna, Stefania; Ambrosio, Maria Rosaria; Doga, Mauro; Gola, Monica; Onofri, Alessandro; Zatelli, Maria Chiara; Giustina, Andrea; degli Uberti, Ettore C

2005-09-01

Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (P<.05) in patients with gigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocity<1) was detected in 2 of 6 patients with gigantism and 1 of 6 patients with acromegaly. Impaired glucose metabolism occurrence was higher in patients with acromegaly (66%) compared with patients with gigantism (16%). Concentrations of IGF-I were significantly (P<.05) higher in patients with gigantism who have cardiac abnormalities than in those without cardiac abnormalities. In conclusion, our data suggest that GH/IGF-I excess in young adult patients is associated with morphologic and functional cardiac abnormalities that are similar in patients with gigantism and in patients with acromegaly, whereas occurrence of impaired glucose metabolism appears to be higher in patients with acromegaly, although patients with gigantism are exposed to GH excess for a longer period.

Nutritional Status and Energy Intake as Predictors of Functional Status After Cardiac Rehabilitation in Elderly Inpatients With Heart Failure　- A Retrospective Cohort Study.

PubMed

Katano, Satoshi; Hashimoto, Akiyoshi; Ohori, Katsuhiko; Watanabe, Ayako; Honma, Remi; Yanase, Rimi; Ishigo, Tomoyuki; Fujito, Takefumi; Ohnishi, Hirofumi; Tsuchihashi, Kazufumi; Ishiai, Sumio; Miura, Tetsuji

2018-05-25

Whether the short-term effect of cardiac rehabilitation (CR) in elderly patients with heart failure (HF) is influenced by nutritional status is uncertain, so the present study investigated the effect of nutritional status on functional recovery after CR in elderly HF inpatients.Methods and Results:We enrolled 145 patients admitted for treatment of HF who were aged ≥65 years and had a low functional status defined as a Barthel index (BI) score ≤85 points at the commencement of CR. Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF) and total energy intake per day. The primary endpoint was functional status determined by the BI score at discharge. The median CR period was 20 days (interquartile range: 14-34 days), and 87 patients (60%) were functionally dependent (BI score ≤85) at discharge. Multivariate logistic regression analysis showed that MNA-SF score (odds ratio [OR]: 0.76, P=0.02) and total energy intake at the commencement of CR (OR: 0.91, P=0.02) were independent predictors of functional dependence after CR. MNA-SF score ≤7 and total energy intake ≤24.5 kcal/kg/day predicted functional dependence at discharge with moderate sensitivity and specificity. MNA-SF score and total energy intake at the commencement of CR are novel predictors of the extent of functional recovery of elderly HF inpatients after in-hospital CR.

Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies.

PubMed

Kanaan, Georges N; Ichim, Bianca; Gharibeh, Lara; Maharsy, Wael; Patten, David A; Xuan, Jian Ying; Reunov, Arkadiy; Marshall, Philip; Veinot, John; Menzies, Keir; Nemer, Mona; Harper, Mary-Ellen

2018-04-01

Glutaredoxin 2 (GRX2), a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC) to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

PubMed

Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

2017-07-01

Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously undiscovered changes in myofibrillar power output were found and were associated with alterations in myofilament proteins, providing potential new targets to exploit for improved ventricular pump function in heart failure. Copyright © 2017 the American Physiological Society.

Simvastatin reduces wasting and improves cardiac function as well as outcome in experimental cancer cachexia.

PubMed

Palus, Sandra; von Haehling, Stephan; Flach, Valerie C; Tschirner, Anika; Doehner, Wolfram; Anker, Stefan D; Springer, Jochen

2013-10-09

Chronic inflammation is common in cancer cachexia (CC) and directly involved in the atrophy seen in this condition. Recently, several groups have described a form of cardiomyopathy in CC animal models. Hence, we investigated the effect of simvastatin with its known anti-inflammatory and cardioprotective effects in a rat model of CC. Juvenile Wister Han rats (weight approx. 200 g) were inoculated with Yoshida AH-130 hepatoma cells and treated once daily with 0.1, 1, 10 or 20 mg/kg/d simvastatin or placebo for 14 days. Body weight and body composition (NMR) were assessed at baseline and at the end of the study. Cardiac function was analysed by echocardiography at baseline and day 11. Tumour-bearing, placebo-treated rats lost 47.9±3.8 g of their initial body weight. Treatment with 0.1, 1, 10 or 20 mg/kg/d simvastatin significantly reduced wasting by 39.6%, 47.6%, 28.5% and 35.4%, respectively (all p<0.05 vs. placebo). This was mainly due to reduced atrophy of lean mass, i.e. muscle mass. Cardiac function was significantly improved, e.g. cardiac output (untreated sham: 78.9 mL/min) was severely impaired in tumour-bearing rats (42.4 mL/min) and improved by 1, 10 or 20 mg/kg/d simvastatin (62.2, 59.0 and 57.0 mL/min, respectively, all p<0.05 vs. placebo). Most importantly, 10 or 20 mg/kg/d simvastatin reduced mortality (HR:0.16, 95%CI:0.04-0.76, p=0.021 and HR:0.16, 95%CI:0.03-0.72, p=0.017 vs placebo, respectively). Simvastatin attenuated loss of body weight as well as muscle mass and improved cardiac function leading to improved survival in this CC model. Simvastatin may be beneficial in a clinical setting to treat CC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Heart rate variability and heart rate turbulence in patients with polycystic ovary syndrome.

PubMed

Özkeçeci, Gülay; Ünlü, Bekir Serdar; Dursun, Hüseyin; Akçi, Önder; Köken, Gülengül; Onrat, Ersel; Avşar, Alaettin

2016-05-01

Cardiac autonomic dysfunction may develop in patients with polycystic ovary syndrome (PCOS). Heart rate variability (HRV) and heart rate turbulence (HRT) are used in assessing cardiac autonomic functions. The goal of this study was to compare the cardiac autonomic functions in patients with PCOS and healthy controls. To our knowledge, this is the first study evaluating cardiac autonomic functions in patients with PCOS with respect to both HRV and HRT. Twenty-three patients with PCOS (mean age 22.8±3.9 years) and 25 healthy female volunteers who were matched for age and body mass index (BMI) (mean age 23.5±6.2 years) were enrolled in this as case-control study. Twenty-four hour ambulatory electrocardiogram recordings of all participants were taken using Pathfinder software. The time domain parameters of HRV and HRT, including turbulence onset (TO) and turbulence slope, were calculated. Diagnosis of PCOS was made with physical and laboratory findings of hirsutism or biochemical hyperandrogenism and chronic anovulation. Diabetes mellitus, other hormon disorders or hormon therapy, pregnancy, atrial fibrilation, obesite, chronic diseases, disorders of the autonomic nervous system, a history of drug use affecting the autonomic nervous system were excluded. There were no significant differences in HRV and HRT parameters between the two groups. Cardiovascular risk factors, such as BMI, blood pressure, fasting blood glucose, and lipid parameters, were also similar. Triangular index measure of HRV was negatively correlated with high density lipoprotein cholesterol levels (r=-0.47, p<0.05), while age and BMI were significantly correlated with TO (r=0.31 and 0.47, respectively; p<0.05 for all). Cardiac autonomic functions were not found to be altered in patients with PCOS in comparison with healthy controls. These results may be explained with the absence of concomitant cardiovascular risk factors with the patients being in the early stage of the disease.

Role of right ventricle and dynamic pulmonary hypertension on determining ΔVO2/ΔWork Rate flattening: insights from cardiopulmonary exercise test combined with exercise echocardiography.

PubMed

Bandera, Francesco; Generati, Greta; Pellegrino, Marta; Donghi, Valeria; Alfonzetti, Eleonora; Gaeta, Maddalena; Villani, Simona; Guazzi, Marco

2014-09-01

Several cardiovascular diseases are characterized by an impaired O2 kinetic during exercise. The lack of a linear increase of Δoxygen consumption (VO2)/ΔWork Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of ΔVO2/ΔWR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants. We studied 136 patients, with different cardiovascular diseases, referred for exertional dyspnoea. Cardiopulmonary exercise test combined with simultaneous exercise echocardiography was performed using a symptom-limited protocol. ΔVO2/ΔWR flattening was observed in 36 patients (group A, 26.5% of population) and was associated with a globally worse functional profile (reduced peak VO2, anaerobic threshold, O2 pulse, impaired VE/VCO2). At univariate analysis, exercise ejection fraction, exercise mitral regurgitation, rest and exercise tricuspid annular plane systolic excursion, exercise systolic pulmonary artery pressure, and exercise cardiac output were all significantly (P<0.05) impaired in group A. The multivariate analysis identified exercise systolic pulmonary artery pressure (odds ratio, 1.06; confidence interval, 1.01-1.11; P=0.01) and exercise tricuspid annular plane systolic excursion (odds ratio, 0.88; confidence interval, 0.80-0.97; P=0.01) as main cardiac determinants of ΔVO2/ΔWR flattening; female sex was strongly associated (odds ratio, 6.10; confidence interval, 2.11-17.7; P<0.01). In patients symptomatic for dyspnea, the occurrence of ΔVO2/ΔWR flattening reflects a significantly impaired functional phenotype whose main cardiac determinants are the excessive systolic pulmonary artery pressure increase and the reduced peak right ventricular longitudinal systolic function. © 2014 American Heart Association, Inc.

The Prevalence, Correlates, and Impact on Cardiac Mortality of Right Ventricular Dysfunction in Nonischemic Cardiomyopathy.

PubMed

Pueschner, Andreas; Chattranukulchai, Pairoj; Heitner, John F; Shah, Dipan J; Hayes, Brenda; Rehwald, Wolfgang; Parker, Michele A; Kim, Han W; Judd, Robert M; Kim, Raymond J; Klem, Igor

2017-10-01

This study sought to determine the prevalence, correlates, and impact on cardiac mortality of right ventricular (RV) dysfunction in nonischemic cardiomyopathy. Current heart failure guidelines place little emphasis on RV assessment due to limited available data on determinants of RV function, mechanisms leading to its failure, and relation to outcomes. We prospectively studied 423 patients with cardiac magnetic resonance (CMR). The pre-specified study endpoint was cardiac mortality. In 100 patients, right heart catheterization was performed as clinically indicated. During a median follow-up time of 6.2 years (interquartile range: 2.9 to 7.6 years), 101 patients (24%) died of cardiac causes. CMR right ventricular ejection fraction (RVEF) was a strong independent predictor of cardiac mortality after adjustment for age, heart failure-functional class, blood pressure, heart rate, serum sodium, serum creatinine, myocardial scar, and left ventricular ejection fraction (LVEF). Patients with the lowest quintile of RVEF had a nearly 5-fold higher cardiac mortality risk than did patients with the highest quintile (hazard ratio: 4.68; 95% confidence interval [CI]: 2.43 to 9.02; p < 0.0001). RVEF was positively correlated with LVEF (r = 0.60; p < 0.0001), and inversely correlated with right atrial pressure (r = -0.32; p = 0.001), pulmonary artery pressure (r = -0.34; p = 0.0005), transpulmonary gradient (r = -0.28; p = 0.006) but not with pulmonary wedge pressure (r = -0.15; p = 0.13). In multivariable logistic regression analysis of CMR, clinical, and hemodynamic data the strongest predictors of right ventricular dysfunction were LVEF (odds ratio [OR]: 0.85; 95% CI: 0.78 to 0.92; p < 0.0001), transpulmonary gradient (OR: 1.20; 95% CI: 1.09 to 1.32; p = 0.0003), and systolic blood pressure (OR: 0.97; 95% CI: 0.94 to 0.99; p = 0.02). CMR assessment of RVEF provides important prognostic information independent of established risk factors and LVEF in heart failure patients with nonischemic cardiomyopathy. Right ventricular dysfunction is strongly associated with both indices of intrinsic myocardial contractility and increased afterload from pulmonary vascular dysfunction. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Continuous Cardiac Troponin I Release in Fabry Disease

PubMed Central

Schneider, Christian; Sieweke, Nicole; Franzen, Wolfgang; Gündüz, Dursun; Rolfs, Arndt

2014-01-01

Background Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD. Methods cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females) regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI). Results Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05–0.71 ng/ml, normal: <0.01). cMRI disclosed late gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3) in cardiomyocytes. Conclusion Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD. PMID:24626231

A comparison study of atlas-based 3D cardiac MRI segmentation: global versus global and local transformations

NASA Astrophysics Data System (ADS)

Daryanani, Aditya; Dangi, Shusil; Ben-Zikri, Yehuda Kfir; Linte, Cristian A.

2016-03-01

Magnetic Resonance Imaging (MRI) is a standard-of-care imaging modality for cardiac function assessment and guidance of cardiac interventions thanks to its high image quality and lack of exposure to ionizing radiation. Cardiac health parameters such as left ventricular volume, ejection fraction, myocardial mass, thickness, and strain can be assessed by segmenting the heart from cardiac MRI images. Furthermore, the segmented pre-operative anatomical heart models can be used to precisely identify regions of interest to be treated during minimally invasive therapy. Hence, the use of accurate and computationally efficient segmentation techniques is critical, especially for intra-procedural guidance applications that rely on the peri-operative segmentation of subject-specific datasets without delaying the procedure workflow. Atlas-based segmentation incorporates prior knowledge of the anatomy of interest from expertly annotated image datasets. Typically, the ground truth atlas label is propagated to a test image using a combination of global and local registration. The high computational cost of non-rigid registration motivated us to obtain an initial segmentation using global transformations based on an atlas of the left ventricle from a population of patient MRI images and refine it using well developed technique based on graph cuts. Here we quantitatively compare the segmentations obtained from the global and global plus local atlases and refined using graph cut-based techniques with the expert segmentations according to several similarity metrics, including Dice correlation coefficient, Jaccard coefficient, Hausdorff distance, and Mean absolute distance error.

Cardiovascular magnetic resonance assessment of acute cardiovascular effects of voluntary apnoea in elite divers.

PubMed

Eichhorn, L; Doerner, J; Luetkens, J A; Lunkenheimer, J M; Dolscheid-Pommerich, R C; Erdfelder, F; Fimmers, R; Nadal, J; Stoffel-Wagner, B; Schild, H H; Hoeft, A; Zur, B; Naehle, C P

2018-06-18

Prolonged breath holding results in hypoxemia and hypercapnia. Compensatory mechanisms help maintain adequate oxygen supply to hypoxia sensitive organs, but burden the cardiovascular system. The aim was to investigate human compensatory mechanisms and their effects on the cardiovascular system with regard to cardiac function and morphology, blood flow redistribution, serum biomarkers of the adrenergic system and myocardial injury markers following prolonged apnoea. Seventeen elite apnoea divers performed maximal breath-hold during cardiovascular magnetic resonance imaging (CMR). Two breath-hold sessions were performed to assess (1) cardiac function, myocardial tissue properties and (2) blood flow. In between CMR sessions, a head MRI was performed for the assessment of signs of silent brain ischemia. Urine and blood samples were analysed prior to and up to 4 h after the first breath-hold. Mean breath-hold time was 297 ± 52 s. Left ventricular (LV) end-systolic, end-diastolic, and stroke volume increased significantly (p < 0.05). Peripheral oxygen saturation, LV ejection fraction, LV fractional shortening, and heart rate decreased significantly (p < 0.05). Blood distribution was diverted to cerebral regions with no significant changes in the descending aorta. Catecholamine levels, high-sensitivity cardiac troponin, and NT-pro-BNP levels increased significantly, but did not reach pathological levels. Compensatory effects of prolonged apnoea substantially burden the cardiovascular system. CMR tissue characterisation did not reveal acute myocardial injury, indicating that the resulting cardiovascular stress does not exceed compensatory physiological limits in healthy subjects. However, these compensatory mechanisms could overly tax those limits in subjects with pre-existing cardiac disease. For divers interested in competetive apnoea diving, a comprehensive medical exam with a special focus on the cardiovascular system may be warranted. This prospective single-centre study was approved by the institutional ethics committee review board. It was retrospectively registered under ClinicalTrials.gov (Trial registration: NCT02280226 . Registered 29 October 2014).