Ishiki R, Ishihara T, Izawa H, Nagata K, Hirai M, Yokota M
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
J Cardiovasc Pharmacol. 2000 Jun;35(6):897-905. doi: 10.1097/00005344-200006000-00011.
A recent long-term multicenter trial has shown that pimobendan is more effective when administered in low doses. However, no data are available concerning the effect of a low dose of pimobendan on the systolic and diastolic pressure-volume relations in patients with heart failure. Therefore we examined the effects of a single low dose of oral pimobendan, a calcium sensitizer, on systolic and diastolic hemodynamics in patients with cardiomyopathy and congestive heart failure. We measured the left ventricular (LV) pressure-volume relations using a conductance catheter with a micromanometer tip in 10 patients with chronic congestive heart failure resulting from idiopathic cardiomyopathy before and 45 and 90 min after administration of a single oral dose of 2.5 mg of pimobendan. End-systolic elastance was used as an index of LV contractility and was measured during transient occlusion of the inferior vena cava. End-systolic elastance increased significantly by 25% at 45 min (p < 0.05) and by 55% at 90 min (p < 0.01) without an increase in myocardial oxygen consumption. The inotropic effect was accompanied by improved ventriculoarterial coupling. This effect was attenuated in patients with severely impaired myocardial contractility. LV relaxation, assessed by the time constant of isovolumic pressure decay (T(1/2)), was significantly shortened at 90 min (from 47.7 +/- 1.9 to 41.2 +/- 1.7 ms; p < 0.01), although it remained unchanged at 45 min. The diastolic pressure-volume relation showed a leftward and downward shift in all patients. These results indicate that low-dose oral pimobendan had favorable short-term inotropic and lusitropic effects in patients with congestive heart failure caused by idiopathic dilated cardiomyopathy, and may thus be a useful alternative to traditional agents. Further study in a large-scale trial is merited.
最近的一项长期多中心试验表明，匹莫苯丹低剂量给药时效果更佳。然而，关于低剂量匹莫苯丹对心力衰竭患者收缩压和舒张压-容积关系的影响尚无数据可用。因此，我们研究了单剂量低剂量口服匹莫苯丹（一种钙敏化剂）对心肌病和充血性心力衰竭患者收缩压和舒张压血流动力学的影响。我们使用带有微压计尖端的电导导管，在10例由特发性心肌病导致的慢性充血性心力衰竭患者中，于单次口服2.5mg匹莫苯丹前以及给药后45分钟和90分钟测量左心室（LV）压力-容积关系。收缩末期弹性用作左心室收缩性的指标，并在短暂阻断下腔静脉期间进行测量。收缩末期弹性在45分钟时显著增加25%（p<0.05），在90分钟时增加55%（p<0.01），而心肌耗氧量未增加。正性肌力作用伴随着心室动脉耦合的改善。在心肌收缩力严重受损的患者中，这种作用减弱。通过等容压力衰减时间常数（T(1/2)）评估的左心室舒张功能在90分钟时显著缩短（从47.7±1.9毫秒缩短至41.2±1.7毫秒；p<0.01），尽管在45分钟时保持不变。所有患者的舒张压-容积关系均向左下方移位。这些结果表明，低剂量口服匹莫苯丹对特发性扩张型心肌病所致充血性心力衰竭患者具有良好的短期正性肌力和变时性作用，因此可能是传统药物的有用替代品。值得在大规模试验中进一步研究。
