Qiu Y, Rizvi A, Tang X L, Manchikalapudi S, Takano H, Jadoon A K, Wu W J, Bolli R
Experimental Research Laboratory, University of Louisville, Kentucky 40292, USA.
Am J Physiol. 1997 Dec;273(6):H2931-6. doi: 10.1152/ajpheart.1997.273.6.H2931.
We tested the hypothesis that late preconditioning (PC) against myocardial infarction is triggered by the formation of nitric oxide (NO). Conscious rabbits underwent a 30-min coronary occlusion followed by 3 days of reperfusion. In group I (control group, n = 10), rabbits were not preconditioned, whereas in group II (n = 10), they were preconditioned 24 h earlier with a sequence of six 4-min occlusion/4-min reperfusion cycles. Myocardial infarct size (tetrazolium staining) was reduced by 50% by PC (28.6 +/- 3.2% of the risk region in group II vs. 56.9 +/- 5.9% in controls, P < 0.05). This reduction in cell death was associated with improved recovery of myocardial function [systolic thickening fraction (by sonomicrometry) at 3 days: 2.0 +/- 11.0% of baseline in group II vs. -20.0 +/- 2.8% in group I, P < 0.05]. Group III rabbits (n = 11) underwent the same protocol as group II except that the rabbits received the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA, 13 mg/kg) before the PC ischemia. In these animals, infarct size did not differ significantly from that observed in control rabbits, indicating that L-NNA completely blocked the development of late PC against myocardial infarction. In group IV (n = 9), rabbits received L-NNA as in group III, but without the six occlusion-reperfusion cycles, and were subjected to the 30-min occlusion 24 h later. In this group, infarct size did not differ from that observed in controls, demonstrating that pretreatment with L-NNA, in itself, did not affect the extent of cell death. Taken together, these results indicate that, in the conscious rabbit, the development of late PC against myocardial infarction is triggered by the generation of NO during the PC ischemia. It is proposed that NO plays a key role in the delayed myocardial adaptation to ischemic stress.
一氧化氮（NO）的生成触发了针对心肌梗死的延迟预处理（PC）。清醒家兔经历30分钟冠状动脉闭塞，随后再灌注3天。在第一组（对照组，n = 10）中，家兔未进行预处理，而在第二组（n = 10）中，它们在24小时前接受了一系列六个4分钟闭塞/4分钟再灌注周期的预处理。通过PC，心肌梗死面积（四氮唑染色）减少了50%（第二组为危险区域的28.6±3.2%，而对照组为56.9±5.9%，P<0.05）。细胞死亡的减少与心肌功能的恢复改善相关[第3天时的收缩期增厚分数（通过超声心动图测量）：第二组为基线的2.0±11.0%，而第一组为-20.0±2.8%，P<0.05]。第三组家兔（n = 11）接受了与第二组相同的方案，不同之处在于这些家兔在PC缺血前接受了一氧化氮合酶抑制剂Nω-硝基-L-精氨酸（L-NNA，13mg/kg）。在这些动物中，梗死面积与对照组家兔相比无显著差异，表明L-NNA完全阻断了针对心肌梗死的延迟PC的发展。在第四组（n = 9）中，家兔如第三组一样接受L-NNA，但没有六个闭塞-再灌注周期，并在24小时后接受30分钟闭塞。在该组中，梗死面积与对照组观察到的无差异，表明用L-NNA预处理本身并不影响细胞死亡程度。综上所述，这些结果表明，在清醒家兔中，针对心肌梗死的延迟PC的发展是由PC缺血期间NO的生成触发的。有人提出，NO在心肌对缺血应激的延迟适应中起关键作用。
