Oliver Michael F
Cardiovascular Research Division, University of Edinburgh, Edinburgh, United Kingdom.
Am J Med. 2002 Mar;112(4):305-11. doi: 10.1016/s0002-9343(01)01104-4.
The mechanisms leading to ventricular fibrillation that occur during acute myocardial ischemia are ill understood. Whether primary ventricular fibrillation is due to a transient imbalance of electrolytes, an alteration of membrane permeability, electrical re-entry phenomena, or other factors, one overriding influence is the development of regional myocardial energy crises. Acute alteration in the balance of substrate supply may lead, during greatly reduced blood flow, to instability of myocardial electrical conduction with the development of re-entry circuits. An immediate response to the angor animi and initial symptoms of an acute coronary syndrome is a rapid and marked increase in catecholamine release, which leads to adipose tissue lipolysis with an acute increase in plasma free fatty acid concentrations, suppression of insulin activity, and a reduction in glucose uptake by the myocardium. The utilization of free fatty acids instead of glucose by the ischemic myocardium could precipitate regional oxygen or energy crises. Prevention therefore should focus on minimizing the catecholamine response and providing the myocardium with an optimum supply of energy substrates. Since catecholamines are inotropic, the aim should be to redress the imbalance of substrate availability by controlling adipose lipolysis with reduction of plasma free fatty acid concentrations, increasing the availability of glucose, or both. Other approaches include inhibition of acylcarnitine transport and manipulation of fatty acid intermediaries. To combat primary ventricular fibrillation, preventive treatment must be established within 6 to 10 hours of the onset of ischemia. There is already experimental and clinical evidence that antilipolytic drugs decrease the incidence of ventricular fibrillation, but their potential has not been explored extensively.
急性心肌缺血期间导致心室颤动的机制尚未完全明了。原发性心室颤动是由于电解质的短暂失衡、膜通透性的改变、电折返现象还是其他因素所致，一个首要的影响因素是局部心肌能量危机的发展。在血流大幅减少期间，底物供应平衡的急性改变可能导致心肌电传导不稳定并形成折返环路。对急性冠脉综合征的心绞痛和初始症状的即时反应是儿茶酚胺释放迅速且显著增加，这会导致脂肪组织脂解，血浆游离脂肪酸浓度急性升高，胰岛素活性受抑制，心肌对葡萄糖的摄取减少。缺血心肌利用游离脂肪酸而非葡萄糖会引发局部氧或能量危机。因此，预防应着重于尽量减少儿茶酚胺反应，并为心肌提供最佳的能量底物供应。由于儿茶酚胺具有正性肌力作用，目标应是通过控制脂肪分解以降低血浆游离脂肪酸浓度、增加葡萄糖的可利用性或两者兼而有之，来纠正底物可利用性的失衡。其他方法包括抑制酰基肉碱转运以及操控脂肪酸中间产物。为对抗原发性心室颤动，必须在缺血发作后6至10小时内开展预防性治疗。已有实验和临床证据表明，抗脂解药物可降低心室颤动的发生率，但其潜力尚未得到广泛探索。
