PHOSPHODIESTERASE-III INHIBITORS - LONG-TERM RISKS AND SHORT-TERM BENEFITS
PHOSPHODIESTERASE-III INHIBITORS - LONG-TERM RISKS AND SHORT-TERM BENEFITS
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DOI：
10.1007/bf00877818
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发表时间：
1993-08-01
影响因子：
3.4
通讯作者：
CRUICKSHANK, JM
中科院分区：
文献类型：
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作者：
CRUICKSHANK, JM
心力衰竭现在被认为是一种循环障碍，而不仅仅是心脏，只有当某些代偿机制崩溃时才会表现出来。在用利尿剂治疗后，治疗心力衰竭的两种主要策略涉及通过血管舒张减少心脏的功或通过正性肌力药物增加心室收缩力。然而，现在很明显，由此产生的血流动力学益处不一定等同于长期临床改善或寿命延长;事实上，反过来也可能是正确的。磷酸二酯酶III的抑制剂，这是具体的环磷酸腺苷（cAMP）的分解，产生有用的血液动力学效应后，静脉内和口服给药，但没有履行其最初的承诺，在慢性口服治疗心力衰竭患者。米力农长期研究中存活率降低的原因尚不清楚，但心律失常可能是由于细胞内cAMP水平升高所致。然而，静脉内使用可能不会受到与长期口服给药相同的限制。短期静脉给药可产生预期的正性肌力和血管舒张的有益血流动力学效应。虽然输注米力农已被证明可以增强房室传导在一些，但不是所有的研究，似乎没有显着增加室性早搏，或室性或持续性快速性心律失常。由于米力农对希氏-浦肯野传导没有显著的不良影响，因此在脑室内传导障碍患者中使用米力农应具有良好的耐受性。然而，短期静脉治疗的死亡风险和获益的准确评估仍有待于足够有力的前瞻性随机对照研究。与此同时，PDE III抑制剂可能适用于需要短期正性肌力支持的精心选择和监测的心力衰竭患者（包括等待手术的潜在心脏移植患者）的短期静脉给药。
Heart failure is now viewed as a disorder of the circulation, not merely the heart, which becomes manifest only when certain compensatory mechanisms break down. After treatment with diuretics, the two main strategies in treating heart failure involve decreasing the work of the heart by vasodilatation or increasing ventricular contractility by positive inotropic agents. It is now apparent, however, that the resulting hemodynamic benefit need not equate with long-term clinical improvement or increased longevity; indeed, the reverse can be true. Inhibitors of phosphodiesterase III, which is specific for the breakdown of cyclic adenosine monophosphate (cAMP), produce useful hemodynamic effects following intravenous and oral dosing, but have not fulfilled their initial promise in the chronic oral treatment of heart failure patients. The reason for reduced survival in the long-term studies of milrinone is not clear, but cardiac arrhythmias, possibly resulting from the increased intracellular levels of cAMP, may be responsible. However, intravenous usage may not suffer from the same limitations as chronic oral dosing. Short-term intravenous administration produces the expected beneficial hemodynamic effects of positive inotropism and vasodilatation. Though infusions of milrinone have been shown to enhance atrioventricular conduction in some, but not all, studies, there appears to be no significant increase in ventricular premature contractions, or ventricular or sustained tachyarrhythmias. Because milrinone does not have a significant adverse effect on His-Purkinje conduction, its use should be well tolerated in patients with intraventricular conduction disturbances. However, accurate assessment of the mortality risk and benefit of short-term intravenous treatment remains to be made in sufficiently powerful prospective, randomized controlled studies. In the meantime, PDE III inhibitors may be suitable for short-term intravenous administration in carefully selected and monitored heart failure patients requiring short-term inotropic support, including potential cardiac transplant patients awaiting surgery.