Schwartz L M, Sebbag L, Jennings R B, Reimer K A
Duke University Medical Center, 409 Elf Street, Durham, NC 27710, USA.
J Mol Cell Cardiol. 2001 Sep;33(9):1561-70. doi: 10.1006/jmcc.2001.1426.
These studies were undertaken to determine the duration of protection against myocardial infarction provided by ischemic preconditioning in the canine heart, and to learn if cardioprotection can be restored by another preconditioning stimulus when the initial effect is lost. Control and four preconditioning groups of anesthetized, open-chest dogs were compared. All underwent a test 60 min episode of ischemia, induced by occlusion of the anterior descending (LAD) artery, followed by 3 h of reperfusion. Preconditioning was induced by one 10 min LAD occlusion, followed by either 10 min, 2, 3, or 5 h of reperfusion. In order to test whether preconditioning could be reinstated, another group of dogs with preconditioning plus 3 h reperfusion underwent a second 10 min preconditioning stimulus with 10 min reperfusion before the 60 min test-occlusion. Infarct size (as percent of area-at-risk) was analyzed (using analysis of covariance) with respect to coronary collateral blood flow measured with radioactive microspheres. Infarct size was limited markedly by preconditioning (23+/-6 v 6+/-2%, P<0.05) but the protective effect was dissipated partially after 2 h reperfusion and was dissipated completely after 3 h reperfusion (20+/-4%, non-significant v Control and significant P<0.05 v preconditioning). Protection was restored in three of six dogs with preconditioning +5 h reperfusion, suggesting that the second window of protection appears early in some canine hearts. When preconditioning was repeated after 3 h reperfusion, cardioprotection was reinstated fully (7+/-2%, P<0.05 v Control and NS v preconditioning). The results show that maximal preconditioning cardioprotection is present in the dog heart after 10 min of reperfusion and is dissipated totally following 3 h of reperfusion. However, a second preconditioning stimulus of 10 min of ischemia followed by 10 min of reperfusion to the dissipated preconditioned heart reinstates full preconditioning. Thus, this model provides a system to test for theoretical causes of the preconditioned state. Final mediators should be present when preconditioning is present and absent when preconditioning is dissipated. It is noteworthy that a second window of protection appeared in 50% of dogs when the period of reperfusion was extended to 5 h.
开展这些研究是为了确定犬心脏缺血预处理提供的抗心肌梗死保护作用的持续时间，并了解当初始效应消失时，心脏保护作用是否能通过另一种预处理刺激得以恢复。对麻醉开胸犬的对照组和四个预处理组进行了比较。所有犬均经历一次由前降支（LAD）动脉闭塞诱导的60分钟缺血发作，随后进行3小时再灌注。预处理通过一次10分钟的LAD闭塞诱导，随后分别进行10分钟、2、3或5小时的再灌注。为了测试预处理是否可以恢复，另一组经过预处理加3小时再灌注的犬在60分钟测试闭塞前，先进行10分钟的第二次预处理刺激并再灌注10分钟。梗死面积（以危险区域面积的百分比表示）通过协方差分析，相对于用放射性微球测量的冠状动脉侧支血流量进行分析。预处理显著限制了梗死面积（23±6%对6±2%，P<0.05），但保护作用在再灌注2小时后部分消失，在再灌注3小时后完全消失（20±4%，与对照组无显著差异，与预处理组有显著差异，P<0.05）。在预处理加5小时再灌注的6只犬中，有3只恢复了保护作用，这表明在一些犬心脏中，第二个保护窗口出现得较早。在再灌注3小时后重复预处理时，心脏保护作用完全恢复（7±2%，与对照组相比P<0.05，与预处理组相比无显著差异）。结果表明，再灌注10分钟后犬心脏中存在最大的预处理心脏保护作用，再灌注3小时后完全消失。然而，对已消失预处理的心脏进行10分钟缺血加10分钟再灌注的第二次预处理刺激可恢复完全的预处理。因此，该模型提供了一个系统来测试预处理状态的理论原因。当存在预处理时应存在最终介质，当预处理消失时应不存在。值得注意的是，当再灌注时间延长至5小时时，50%的犬出现了第二个保护窗口。
