Lee H C, Lum B K
Circ Shock. 1986;18(3):193-203.
Calcium entry blockers (CEBs) have been reported to protect against cellular necrosis caused by experimental ischemia and the beneficial effect has been related to prevention of ischemia-induced calcium overload by the CEBs. Since circulatory shock can be expected to produce generalized tissue hypoxia, the possibility that CEBs might be beneficial in shock produced by endotoxin was investigated. In control male Wistar rats, a 10-mg/kg dose of E. coli endotoxin (Difco 0127:B8) produced a fall in blood pressure and a transient increase followed by a progressive slowing of the heart rate. Mortality 48 hours after endotoxin (10 mg/kg) was 84%. The calcium entry blockers (CEBs) verapamil, nitrendipine, and nilvadipine [corrected], administered i.v. 15 min before endotoxin, produced a dose-dependent reduction in mortality. The CEBs were less effective when given as post-treatment (15 to 30 min after endotoxin). Measurements of total tissue and mitochondrial calcium levels in control rats revealed that endotoxin did not produce an increase in the calcium content of heart, lung, pancreas, small intestine, kidney, and aorta. Since increased cellular calcium levels did not occur in response to endotoxin, the protection induced by CEBs in endotoxin shock does not appear to be related to prevention of calcium overload; however, the possibility that the CEBs may beneficially prevent an excessive accumulation of calcium in discrete cells or intracellular compartments (which may not be detected by our methods) cannot be excluded.
据报道，钙通道阻滞剂（CEBs）可保护细胞免受实验性缺血所致的坏死，其有益作用与CEBs预防缺血诱导的钙超载有关。由于循环性休克预计会导致全身性组织缺氧，因此研究了CEBs在内毒素所致休克中可能有益的可能性。在对照雄性Wistar大鼠中，10 mg/kg剂量的大肠杆菌内毒素（Difco 0127:B8）可导致血压下降，心率短暂升高，随后逐渐减慢。内毒素（10 mg/kg）注射后48小时的死亡率为84%。在内毒素注射前15分钟静脉注射钙通道阻滞剂维拉帕米、尼群地平和尼伐地平[校正后]，可产生剂量依赖性的死亡率降低。在内毒素注射后（内毒素注射后15至30分钟）进行治疗时，CEBs的效果较差。对对照大鼠的全组织和线粒体钙水平进行测量发现，内毒素并未导致心脏、肺、胰腺、小肠、肾脏和主动脉的钙含量增加。由于内毒素刺激并未导致细胞钙水平升高，因此CEBs在内毒素休克中诱导的保护作用似乎与预防钙超载无关；然而，不能排除CEBs可能有益地预防离散细胞或细胞内区室中钙过度蓄积的可能性（这可能无法通过我们的方法检测到）。
