Ohte N, Cheng C P, Suzuki M, Little W C
Cardiology Section, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1045, USA.
J Pharmacol Exp Ther. 1997 Jul;282(1):23-31.
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 microg/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.
我们比较了匹莫苯丹（静脉注射0.25mg/kg）（一种具有某些磷酸二酯酶III抑制作用的钙离子增敏剂）和氨力农（静脉注射1mg/kg加10μg/kg/min）（一种磷酸二酯酶III抑制剂）对7只清醒犬在起搏诱导的充血性心力衰竭（CHF）前后静息和运动状态下左心室（LV）收缩和舒张功能的影响。在CHF之前，静息状态下，匹莫苯丹和氨力农均使左心室大小、收缩末期压力、动脉弹性和左心室舒张时间常数显著下降。运动时也得到了类似结果。两种药物还使E(ES)（左心室收缩末期压力-容积关系的斜率）有类似增加（氨力农组为3.4±1.5mmHg/ml，匹莫苯丹组为4.2±1.1mmHg/ml）。CHF后，氨力农和匹莫苯丹的血管舒张作用在静息和运动时均得以保留；然而，它们的正性肌力作用有所不同。CHF后，匹莫苯丹增加了E(ES)（从3.9±0.5mmHg/ml增加到5.7±0.4mmHg/ml，P<0.05），降低了左心室舒张时间常数，增加了左心室最大充盈速率（37±19ml/秒）（P<0.05），并使左心室压力-容积环舒张早期部分向下移位。匹莫苯丹在CHF运动期间还增强了左心室收缩功能。相比之下，CHF后，氨力农不再产生正性肌力作用。氨力农改善了CHF后静息和运动时的左心室舒张和充盈，但显著低于匹莫苯丹。我们得出结论，CHF后，心脏对磷酸二酯酶III抑制剂的反应减弱，但对钙离子增敏剂的反应得以保留。因此，CHF后，匹莫苯丹在增强静息和运动时的左心室收缩状态、左心室舒张和左心室充盈方面比氨力农更有效。
