Nayler W G
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Drugs. 1992;43 Suppl 1:21-7. doi: 10.2165/00003495-199200431-00006.
Calcium antagonists are useful for the management of patients with ischaemic heart disease, particularly when used prophylactically. At the cellular level, these drugs act primarily by limiting calcium ion (Ca++) entry through the voltage-sensitive Ca(++)-selective channels, an effect that contributes markedly to their 'energy sparing' properties. However, the long term use of these drugs has additional advantages, particularly with respect to their ability to slow Ca(++)-dependent processes involved in the formation of atherogenic lesions, partially antagonise the effects of the raised levels of circulating endothelin-1 encountered during ischaemia-induced heart failure and hypertension, and trap and immobilise oxyradicals. Prolonged episodes of ischaemia result in an irreversible loss of homeostasis with respect to Ca++. However, the increase in myocardial cytosolic Ca++ caused by relatively short periods of ischaemia is small, reversible, and markedly attenuated by the prophylactic use of calcium antagonists. In the isolated, perfused rat heart, verapamil pretreatment produces statistically significant inhibition of the increase in cytosolic Ca++ during 20-minute global ischaemia. This stereospecific effect is associated with a decrease in the rise in total tissue Ca++ during reperfusion and amelioration of the adenosine triphosphate depletion caused by ischaemia. In general, discussion relating to the molecular basis of the use of calcium antagonists in the management of patients with ischaemic heart disease needs to take into account the duration of the ischaemic event, the workload on the myocardium, the need for prophylactic therapy, and the presence of exacerbating factors such as atherosclerosis and tobacco smoking. The early rise in cytosolic Ca++, the source of which remains uncertain, appears to be an important focus for anti-ischaemic drug therapy.
钙拮抗剂对缺血性心脏病患者的治疗很有用，尤其是预防性使用时。在细胞水平上，这些药物主要通过限制钙离子（Ca++）通过电压敏感的Ca（++）选择性通道进入细胞起作用，这一作用对它们的“节省能量”特性有显著贡献。然而，这些药物的长期使用还有其他优点，特别是在减缓参与动脉粥样硬化病变形成的Ca（++）依赖性过程、部分拮抗缺血性心力衰竭和高血压期间循环内皮素-1水平升高的影响以及捕获和固定氧自由基方面。长时间的缺血会导致Ca++内环境稳定的不可逆丧失。然而，相对较短时间的缺血引起的心肌细胞溶质Ca++增加较小、可逆，并且通过预防性使用钙拮抗剂可明显减弱。在离体灌注大鼠心脏中，维拉帕米预处理可在统计学上显著抑制20分钟全心缺血期间细胞溶质Ca++的增加。这种立体特异性作用与再灌注期间总组织Ca++升高的减少以及缺血引起的三磷酸腺苷耗竭的改善有关。一般来说，关于在缺血性心脏病患者治疗中使用钙拮抗剂的分子基础的讨论需要考虑缺血事件的持续时间、心肌的工作量、预防性治疗的必要性以及是否存在动脉粥样硬化和吸烟等加重因素。细胞溶质Ca++的早期升高（其来源尚不确定）似乎是抗缺血药物治疗的一个重要靶点。
