Cardiomyocyte contractility and calcium handling partially recover after early deterioration during post‐infarction failure in rat

Abstract

The aim of the study was to determine whether progression of heart failure is associated with deterioration of cardiomyocyte function. Cell dimensions, contractility and calcium transients were measured in cardiomyocytes isolated from the left ventricle of female Wistar rats 1, 4, and 13 weeks after coronary artery ligation or sham-operation. Relative cardiomyocyte shortening decreased from 26% in controls to 11% 1 week after myocardial infarction and recovered to 18 and 20% after 4 and 13 weeks, respectively. Diastolic and systolic calcium concentrations increased markedly 1 week after myocardial infarction with subsequent reduction after 4 and 13 weeks. Time to 50% relaxation was prolonged by 31% after 1 week and 20% after 4 and 13 weeks with corresponding changes in diastolic calcium clearance. Cardiomyocyte length increased by 6, 24, and 26% after 1, 4 and 13 weeks, respectively, whereas myocyte width increased by 4, 11 and 27%. Cardiomyocytes adjacent to the infarct hypertrophied more and initially had more markedly impaired function than in the remote area. Left ventricular diastolic diameter assessed by echocardiography increased by 47, 66 and 84% after 1, 4 and 13 weeks, respectively, and systolic diameter increased by 120, 162 and 194%. Left ventricular end-diastolic pressure increased from 6 mmHg to 24, 25 and 36 mmHg. Whereas initial deterioration of cardiac function is associated with reduced cardiomyocyte contractile function, chronic heart failure progression is not accompanied by further impairment of intrinsic cardiomyocyte contractility in this model. Cardiomyocyte hypertrophy and dysfunction are more marked adjacent to the infarction.

Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure

“…Rat model of chronic post-infarction cardiomyopathy was used as it is a well established reproducible model of dysfunction. 22,23 Syngeneic rat strains avoid the need for immunosuppression after abdominal transplantation. Therefore, male Lewis rats (200–300 g) were used for all experiments.…”

High-Intensity Aerobic Exercise Training Improves the Heart in Health and Disease

“…19 Cardiomyocytes isolated from HF animals show dysfunctional excitation, Ca 2ϩ handling, and contraction; abnormal cellular structure and architecture; and a pathological hypertrophy that is greater than the physiological hypertrophy observed after exercise training in healthy counterparts. 20,21 These changes explain the reduced ability of the cardiomyocyte and the whole heart to perform beat-to-beat contractile work. Importantly, they are also prone to positive modulation by exercise training; in fact, regular aerobic exercise training has been demonstrated to correct and reverse at least some of the pathological alterations in the cardiomyocyte and more so after high-intensity exercise training programs at approximately 90% of V .…”

Aerobic Fitness Is Associated With Cardiomyocyte Contractile Capacity and Endothelial Function in Exercise Training and Detraining

“…Although stroke volume is acutely regulated by extracardiac factors such as venous return, neurohormonal regulation, and afterload, previous studies identified significant correlation between contractile function of isolated myocytes and integrated in vivo function, indicating a contribution of intrinsic myocardial properties as well at both the molecular 29 and cellular levels. 6,18,30 Both statistical correlation and parallel time courses indicate that changes in cardiomyocyte size and function are likely to account for the changes in V O 2 max. Because of the high internal correlations between different measures of cardiomyocyte size and function, it is to be expected that only 1 or 2 prove to be significant in multivariate regression analysis.…”