Levosimendan preserves systolic and diastolic function in rats with volume overload heart failure through myofilament Ca2+ sensitization and regulatory protein phosphorylation (1081.4)

Objectives. This study investigated whether early intervention with the myofilament Ca2+ sensitizer levosimendan (Levo) could preserve cardiac function in aortocaval fistula (ACF)-induced volume overload (VO). Methods and Results. ACF or sham surgery was performed in male Sprague-Dawley rats (200-240g) 4 weeks prior to initiating treatment with Levo (1 mg/kg/day in drinking water) or vehicle (Veh; water) for 4 weeks. Even with continued VO and compared with ACF-Veh, Levo improved systolic (%FS, Ees, PRSW; 41.3 vs 32.2%, p<0.0001; 0.654 vs 0.392 mmHg/µL, p<0.05; 113.6 vs 60.2 mmHg, p<0.05, respectively) and diastolic (tau, dP/dtmin; 8.9 vs 10.8 msec, p<0.05; -7626 vs -5739 mmHg/sec, p<0.001, respectively) function without significant LV remodeling. Additionally, Levo treatment resulted in 1) improved myofilament Ca2+ sensitivity without significantly affecting the amplitude and kinetics of the myocyte intracellular Ca2+ transient; 2) preserved in vivo β-adrenergic responsiveness; and 3) increased phosphory...