Daleau P, Boudriau S, Michaud M, Jolicoeur C, Kingma J G
Quebec Heart Institute, Laval Hospital, Ste-Foy, Canada.
Can J Physiol Pharmacol. 2001 May;79(5):371-8.
In the heart, brief repeated episodes of ischemia prior to a sustained occlusion (ischemic preconditioning; PC) significantly delay the onset of necrosis and arrhythmogenesis. Ischemia has been reported to influence gap junction organization and connexin43 (Cx43) content, but whether PC affects these structures is not known. We investigated the effect of PC (2 cycles of 5-min ischemia plus 10-min reperfusion) followed by prolonged reperfusion without concomitant regional coronary occlusion on the myocardial Cx43 content and its spatial distribution in rabbit hearts. We also compared the effect of sustained ischemia with or without PC on Cx43 spatial distribution. In experiments with PC only, there was an initial decrease in Cx43 levels within the ischemic zone followed by a progressive increase after 48 h reperfusion. End-to-end immunolabeling of Cx43 was augmented in the ischemic region between 24 and 48 h reperfusion; labeling was not uniquely confined to myocyte abutments, but was also dispersed along the sarcolemma. Cx43 immunolabelling was more intense and diffuse in hearts subjected to PC before sustained coronary occlusion (compared to non-PC). These data indicate that gap junctions are significantly altered during brief episodes of ischemia. Reorganization of the gap junction complex could contribute to PC-mediated reductions in cardiac arrhythmias.
在心脏中，在持续性闭塞之前的短暂反复缺血发作（缺血预处理；PC）会显著延迟坏死和心律失常的发生。据报道，缺血会影响缝隙连接的组织和连接蛋白43（Cx43）的含量，但PC是否会影响这些结构尚不清楚。我们研究了PC（5分钟缺血加10分钟再灌注的2个周期）后，在没有伴随区域性冠状动脉闭塞的情况下进行长时间再灌注对兔心肌Cx43含量及其空间分布的影响。我们还比较了有或没有PC的持续性缺血对Cx43空间分布的影响。在仅进行PC的实验中，缺血区内Cx43水平最初下降，随后在再灌注48小时后逐渐升高。在再灌注24至48小时之间，缺血区域内Cx43的端对端免疫标记增加；标记不仅局限于心肌细胞邻接处，还沿肌膜分散。与未进行PC的心脏相比，在持续性冠状动脉闭塞之前进行PC的心脏中，Cx43免疫标记更强且更弥散。这些数据表明，在短暂缺血发作期间，缝隙连接会发生显著改变。缝隙连接复合物的重组可能有助于PC介导的心律失常减少。
