Effects of a myofilament calcium sensitizer on left ventricular systolic and diastolic function in rats with volume overload heart failure

This study investigated myocyte and myofilament function in ACF and REV and tested the hypothesis that a myofilament Ca2+ sensitizer would improve VO-induced myofilament dysfunction in ACF and REV. Following the initial sham or ACF surgery in male Sprague-Dawley rats (200–240 g) at week 0, REV surgery and experiments were performed at weeks 4 and 8, respectively. In ACF, decreased LV function is accompanied by impaired sarcomeric shortening and force generation and decreased Ca2+ sensitivity, whereas, in REV, impaired LV function is accompanied by decreased Ca2+ sensitivity. Intravenous levosimendan (Levo) elicited the best inotropic and lusitropic responses and was selected for chronic oral studies. Subsets of ACF and REV rats were given vehicle (water) or Levo (1 mg/kg) in drinking water from weeks 4–8. Levo improved systolic (% fractional shortening, end-systolic elastance, and preload-recruitable stroke work) and diastolic (, dP/dtmin) function in ACF and REV. Levo improved Ca2+ sensitivity without altering the amplitude and kinetics of the intracellular Ca2+ transient. In ACF-Levo, increased cMyBP-C Ser-273 and Ser-302 and cardiac troponin I Ser-23/24 phosphorylation correlated with improved diastolic relaxation, whereas, in REV-Levo, increased cMyBP-C Ser-273 phosphorylation and increased α-to-β-myosin heavy chain correlated with improved diastolic relaxation. We concluded that Levo improves LV function, and myofilament composition and regulatory ...

Source: AJP: Heart and Circulatory Physiology - December 1, 2014 Category: Cardiology Authors: Wilson, K., Guggilam, A., West, T. A., Zhang, X., Trask, A. J., Cismowski, M. J., de Tombe, P., Sadayappan, S., Lucchesi, P. A. Tags: MUSCLE MECHANICS AND VENTRICULAR FUNCTION Source Type: research