EFFECTS OF EMD-57033 ON CONTRACTION AND RELAXATION IN ISOLATED RABBIT HEARTS

Background Ca2+ sensitizers are reported to enhance contractility with modest effects on energy utilization. In the present study we assessed the effects of the relatively ''pure'' Ca2+ sensitizer EMD 57033 on mechanical performance and energy consumption in the beating heart. Methods and Results In 10 isolated, red blood cell-perfused rabbit hearts the effects of EMD 57033 (5.0 to 5.8 mu mol/L) on left ventricular (LV) pressure and O-2 consumption (Vo(2)) Were examined at heart rates of 100 and 150 beats per minute (bpm) and perfusate [Ca2+] ([Ca2+](o)) of 2.5 and 1.0 mmol/L (isovolumic contractions). LV developed pressure and maximum dP/dt increased, but less so at 150 bpm or 1.0 mmol/L [Ca2+](o). End-diastolic pressure also increased, more so at 150 bpm or 1.0 mmol/L [Ca2+](o). EMD 57033 decreased time to peak isovolumic pressure (T-max) and prolonged time to 50% pressure decline (T-1/2). These changes were greater at slower heart rate or lower [Ca2+](o). The magnitude of increased Vo(2) with EMD 57033 was greater at 100 bpm than 150 bpm but unaffected by [Ca2+](o). We then investigated the influence of ejection on the response to EMD 57033 (n=7). The increase in developed pressure with EMD 57033 was greater for ejecting than isovolumic beats (25.5+/-10.2 versus 14.7+/-7.5 mm Hg at 100 bpm, P<.01), while the increase in end-diastolic pressure was less (P=NS). The increase in Vo(2) was significantly greater for ejecting than isovolumic beats (0.027+/-0.013 versus 0.020+/-0.009 mL O-2/beat per 100 g at 100 bpm, P<.01). Conclusions EMD 57033 enhances contractility and prolongs relaxation. its effects are modulated by heart rate, [Ca2+](o). and contraction mode, with positive inotropic effects being more prominent for ejecting beats.