Przyklenk K, Hata K, Kloner R A
Heart Institute, Hospital of the Good Samaritan, and Department of Medicine, University of Southern California, Los Angeles 90017, USA.
Circulation. 1997 Aug 19;96(4):1305-12. doi: 10.1161/01.cir.96.4.1305.
The cellular mechanisms by which brief episodes of ischemia protect or "precondition" the heart and limit infarct size caused by a later period of sustained coronary artery occlusion remain unresolved. We propose that calcium may be an important mediator in eliciting this cardioprotection.
To test this hypothesis, anesthetized dogs received a 15-minute intracoronary infusion of 20 mmol/L CaCl2 or saline before undergoing 1 hour of coronary occlusion and 4 hours of reperfusion (protocol 1). Collateral blood flow during occlusion was measured with radiolabeled microspheres, area at risk of infarction (AR) was delineated by injection of blue dye, and area of necrosis (AN) was determined by tetrazolium staining. AN/AR was reduced from 20+/-5% in the saline-treated controls to 9+/-3% in CaCl2-treated dogs (P<.05). Additional animals underwent 10 minutes of preconditioning ischemia or a comparable waiting period before the 1-hour test occlusion (protocol 2). Administration of 5-(N,N-dimethyl)-amiloride (an inhibitor of calcium influx via Na+-H+ and Na+-Ca2+ exchange) before the preconditioning stimulus attenuated the protective effect of ischemic preconditioning: AN/AR was 12+/-1%, larger than the value of 4+/-1% observed in preconditioned dogs that received saline (P<.05) and comparable to the values of 12+/-3% and 14+/-3% seen in saline- and dimethylamiloride-treated controls.
Brief intracoronary infusion of CaCl2 mimicked, whereas treatment with dimethylamiloride blocked, infarct size reduction with preconditioning, thereby implicating calcium as a mediator of preconditioning in this canine model.
短暂性缺血保护或“预处理”心脏以及限制随后持续性冠状动脉闭塞所导致梗死面积的细胞机制仍未明确。我们提出钙可能是引发这种心脏保护作用的重要介质。
为验证这一假说，麻醉后的犬在经历1小时冠状动脉闭塞和4小时再灌注之前，接受15分钟冠状动脉内输注20 mmol/L氯化钙或生理盐水（方案1）。用放射性微球测量闭塞期间的侧支血流，通过注射蓝色染料勾勒出梗死危险区（AR），并用四氮唑染色确定坏死面积（AN）。AN/AR从生理盐水处理的对照组的20±5%降至氯化钙处理的犬的9±3%（P<0.05）。另外的动物在1小时试验性闭塞之前先经历10分钟预处理缺血或相当的等待期（方案2）。在预处理刺激之前给予5-（N，N-二甲基）阿米洛利（一种通过Na+-H+和Na+-Ca2+交换抑制钙内流的抑制剂）减弱了缺血预处理的保护作用：AN/AR为12±1%，大于接受生理盐水的预处理犬所观察到的4±1%的值（P<0.05），且与生理盐水和二甲基阿米洛利处理的对照组所观察到的12±3%和14±3%的值相当。
冠状动脉内短暂输注氯化钙模拟了预处理对梗死面积的缩小作用，而用二甲基阿米洛利处理则阻断了这种作用，从而表明在该犬模型中钙是预处理的介质。
