Remme W J
Sticares Foundation, Rotterdam, The Netherlands.
Eur Heart J. 1998 Sep;19 Suppl J:J16-23.
Long-term controlled trials in heart failure in patients with asymptomatic left ventricular dysfunction indicate the potential of ACE inhibition to reduce ischaemic events, such as unstable angina and myocardial infarction. These effects occur after long-term medication and suggest structural rather than functional effects of ACE inhibitors. Such structural effects could include an improvement in endothelial function and less atherosclerosis of coronary and systemic arteries, as well as a reduction in cardiac size. Together, these effects may improve the myocardial oxygen supply/demand ratio. Neurohormonal activation is pivotal in heart failure and also occurs in patients with asymptomatic left ventricular dysfunction. ACE inhibitors modulate neurohormonal activation and, through that mechanism, may induce their beneficial effects in terms of cardiac remodelling and improved morbidity and mortality in heart failure patients. Neurohormonal activation also occurs during acute myocardial infarction, particularly in patients with diminished left ventricular dysfunction or heart failure. Recent studies indicate that short episodes of stress-induced myocardial ischaemia may also lead to significant increases in circulating norepinephrine, epinephrine and, in more severe ischaemia, in angiotensin II. This increase in vasoconstricting neurohormones results in significant systemic vasoconstriction and may also underlie the constriction of abnormal coronary segments observed during atrial pacing-induced stress. This ischaemia-induced neurohormonal activation is not dependent on the stress of angina, but correlates with the degree of myocardial ischaemia and also with the presence of left ventricular dysfunction. Acute ACE inhibition modulates this ischaemia-induced neurohormonal activation and the subsequent effects on systemic and coronary vascular tone. Consequently, acute ACE inhibition significantly reduces acute myocardial ischaemia. The significance of these observations is as yet unclear. However, they may be important in situations of severe myocardial ischaemia, such as unstable angina and acute myocardial infarction. Presumably, this potential of ACE inhibitors to reduce short-term stress-induced myocardial ischaemia as a result of their neurohormonal modulating and subsequent vasodilating effects gains in significance during chronic ACE inhibitor treatment, in parallel with a long-term improvement of coronary endothelial function.
针对无症状左心室功能不全患者的心力衰竭长期对照试验表明，血管紧张素转换酶（ACE）抑制剂具有降低缺血性事件（如不稳定型心绞痛和心肌梗死）的潜力。这些作用在长期用药后出现，提示ACE抑制剂的作用是结构性而非功能性的。这种结构性作用可能包括内皮功能改善、冠状动脉和全身动脉粥样硬化减轻以及心脏大小减小。综合起来，这些作用可能改善心肌氧供/需求比。神经激素激活在心力衰竭中起关键作用，在无症状左心室功能不全患者中也会发生。ACE抑制剂可调节神经激素激活，并通过该机制在心脏重塑以及改善心力衰竭患者的发病率和死亡率方面发挥有益作用。神经激素激活在急性心肌梗死期间也会发生，尤其是在左心室功能不全或心力衰竭程度较轻的患者中。最近的研究表明，短期应激诱导的心肌缺血发作也可能导致循环中的去甲肾上腺素、肾上腺素显著增加，在更严重的缺血情况下，血管紧张素II也会增加。血管收缩性神经激素的这种增加会导致显著的全身血管收缩，也可能是心房起搏诱导应激期间观察到的异常冠状动脉节段收缩的原因。这种缺血诱导的神经激素激活不依赖于心绞痛的应激，而是与心肌缺血程度以及左心室功能不全的存在相关。急性ACE抑制可调节这种缺血诱导的神经激素激活以及随后对全身和冠状动脉血管张力的影响。因此，急性ACE抑制可显著减轻急性心肌缺血。这些观察结果的意义尚不清楚。然而，它们在严重心肌缺血的情况下（如不稳定型心绞痛和急性心肌梗死）可能很重要。据推测，ACE抑制剂由于其神经激素调节和随后的血管舒张作用而降低短期应激诱导心肌缺血的潜力，在慢性ACE抑制剂治疗期间会变得更加重要，同时冠状动脉内皮功能也会得到长期改善。
