Abstract

We compared the effects of pimobendan (0.25 mg/kg i.v.), a Ca⁺⁺ sensitizer, with some phosphodiesterase-III inhibition effects, and amrinone (1 mg/kg plus 10 μg/kg/min i.v.), a PDE-III inhibitor, on left ventricular (LV) systolic and diastolic performance, both at rest and during exercise, in seven conscious dogs before and after pacing-induced congestive heart failure (CHF). Before CHF, under resting conditions, both pimobendan and amrinone caused a similar significant decrease in left ventricle size and end-systolic pressure, arterial elastance, and the time constant of LV relaxation. Similar results were obtained during exercise. Both agents also produced a similar increase in E _ES, the slope of the LV end-systolic pressure-volume relation (3.4 ± 1.5 vs.4.2 ± 1.1 mm Hg/ml; amrinone vs. pimobendan). After CHF, the vasodilatory effects of amrinone and pimobendan were preserved both at rest and during exercise; however, the inotropic actions were different. After CHF, pimobendan increased E _ES(3.9 ± 0.5 vs. 5.7 ± 0.4 mm Hg/ml, P < .05), decreased the time constant of LV relaxation, increased the maximum rate of LV filling (37 ± 19 ml/sec) (P < .05) and produced a downward shift of the early diastolic portion of LV pressure-volume loop. Pimobendan also augmented LV contractile performance during CHF exercise. In contrast, after CHF, amrinone no longer produced a positive inotropic effect. Amrinone improved LV relaxation and filling, both at rest and during exercise after CHF, but significantly less than pimobendan. We conclude that after CHF, the cardiac response to a PDE-III inhibitor is attenuated, but the response to Ca⁺⁺ sensitizer is preserved. Thus, after CHF, pimobendan is more effective than amrinone in enhancing LV contractile state, LV relaxation and LV filling both at rest and during exercise.