THE CARDIAC EFFECTS OF PIMOBENDAN (BUT NOT AMRINONE) ARE PRESERVED ATREST AND DURING EXERCISE IN CONSCIOUS DOGS WITH PACING-INDUCED HEART-FAILURE

We compared the effects of pimobendan (0.25 mg/kg i.v.), a Ca++ sensit izer, with some phosphodiesterase-III inhibition effects, and amrinone (1 mg/kg plus 10 mu g/kg/min i.v.), a PDE-III inhibitor, on left vent ricular (LV) systolic and diastolic performance, both at rest and duri ng exercise, in seven conscious dogs before and after pacing-induced c ongestive heart failure (CHF). Before CHF, under resting conditions, b oth pimobendan and amrinone caused a similar significant decrease in l eft ventricle size and end-systolic pressure, arterial elastance, and the time constant of LV relaxation. Similar results were obtained duri ng 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 vasod ilatory effects of amrinone and pimobendan were preserved both at rest and during exercise; however, the inotropic actions were different. A fter 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 produ ced a downward shift of the early diastolic portion of LV pressure-vol ume loop. Pimobendan also augmented LV contractile performance during CHF exercise. In contrast, after CHF, amrinone no longer produced a po sitive inotropic effect. Amrinone improved LV relaxation and filling, both at rest and during exercise after CHF, but significantly less tha n pimobendan. We conclude that after CHF, the cardiac response to a PD E-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.