Puschett J B
Department of Medicine, University of Pittsburgh School of Medicine, Pa.
Am J Nephrol. 1987;7 Suppl 1:49-56. doi: 10.1159/000167543.
Data from several studies have indicated that calcium channel blockers may prevent acute renal damage caused by ischemia. If this is true, then the obvious clinical application of this premise would be in surgical cases requiring cross-clamping of the aorta, or in patients experiencing prolonged hypotension. Evidence for the mechanism by which calcium channel blockers mitigate injury include the prevention or amelioration of renal vasoconstriction and/or their ability to inhibit calcium entry into cells, thereby possibly preventing toxic calcium 'overload'. Studies of animal models examining ischemic acute renal failure produced either by infusion of vasoconstrictors or by interrupting renal artery blood flow have provided conflicting results. Certain calcium channel blockers afford some degree of protection only when administered prior to the ischemic episode, while others may protect even if given after the insult. Several investigations have been carried out to determine the mechanism(s) of this protective effect. The results indicate cellular calcium accumulation occurs in cells during the anoxic period; this is most pronounced during reflow. This accumulation of calcium appears to be temporally related to both mitochondrial dysfunction and cell death. The ability of the calcium channel blockers to prevent calcium entry into cells may explain their role in protecting the cell and ameliorating ischemic injury.
多项研究的数据表明，钙通道阻滞剂可能预防缺血所致的急性肾损伤。如果这一情况属实，那么该前提在临床上的明显应用将是在需要夹闭主动脉的手术病例中，或者是在经历长时间低血压的患者中。钙通道阻滞剂减轻损伤的机制证据包括预防或改善肾血管收缩和/或其抑制钙进入细胞的能力，从而可能预防毒性钙“超载”。对通过输注血管收缩剂或中断肾动脉血流产生缺血性急性肾衰竭的动物模型的研究得出了相互矛盾的结果。某些钙通道阻滞剂仅在缺血发作前给药时才提供一定程度的保护，而其他一些即使在损伤后给药也可能起到保护作用。已经进行了多项研究以确定这种保护作用的机制。结果表明，细胞内钙在缺氧期会发生积累；这在再灌注期间最为明显。钙的这种积累似乎在时间上与线粒体功能障碍和细胞死亡都相关。钙通道阻滞剂阻止钙进入细胞的能力可能解释了它们在保护细胞和减轻缺血性损伤中的作用。
