Struthers A D
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, U.K.
Eur Heart J. 1995 Dec;16 Suppl N:103-6. doi: 10.1093/eurheartj/16.suppl_n.103.
In the setting of chronic heart failure (CHF), therapy with angiotensin converting enzyme (ACE) inhibitors generally reduces serum aldosterone levels acutely. However, long-term ACE inhibition is associated with aldosterone suppression that is weak, variable, and unsustained, i.e. aldosterone 'escape'. Magnesium loss caused by aldosterone and by diuretics can contribute to coronary artery spasm and arrhythmias. Aldosterone can block noradrenaline uptake by the myocardium; extracellular catecholamines may lead to arrhythmias and ischaemia. Aldosterone has been shown to have an acute arrhythmogenic effect as well as a potential detrimental effect on baroreflex function, a marker of prognosis in CHF. Both angiotensin II and aldosterone may stimulate myocardial fibrosis, which is associated with a higher incidence of malignant ventricular arrhythmias. ACE inhibition initiated early in the progression of CHF may prevent development of patchy myocardial fibrosis and its inherent arrhythmias and thus reduce the incidence of sudden death. Spironolactone therapy added to the regimen of an ACE inhibitor and diuretic can induce natriuresis and magnesium retention, increase myocardial noradrenaline uptake, and reduce the incidence of arrhythmias.
在慢性心力衰竭（CHF）的情况下，使用血管紧张素转换酶（ACE）抑制剂进行治疗通常会使血清醛固酮水平迅速降低。然而，长期抑制ACE会导致醛固酮抑制作用微弱、多变且难以持续，即醛固酮“逃逸”。醛固酮和利尿剂引起的镁流失可导致冠状动脉痉挛和心律失常。醛固酮可阻断心肌对去甲肾上腺素的摄取；细胞外儿茶酚胺可能导致心律失常和缺血。已表明醛固酮具有急性致心律失常作用，以及对压力反射功能（CHF预后的一个指标）的潜在有害作用。血管紧张素II和醛固酮均可刺激心肌纤维化，而心肌纤维化与恶性室性心律失常的发生率较高有关。在CHF进展早期开始使用ACE抑制剂可预防斑片状心肌纤维化及其固有心律失常的发生，从而降低猝死的发生率。在ACE抑制剂和利尿剂治疗方案中加用螺内酯可诱导利钠和镁潴留，增加心肌对去甲肾上腺素的摄取，并降低心律失常的发生率。
