Cardioprotective effect of ischemic preconditioning on cyanotic myocardium and its relation to Heat Shock Protein

背景/目的：缺血预处理（IP）被认为可以保护心脏免受缺血和再灌注损伤。然而，这种现象的机制仍然未知。因此，我们研究了IP的心肌保护作用及其与cGMP的关系，在离体灌注工作heartmodel.METHODS：18个心脏从雄性Wister大鼠被放置在Langendorff电路，并进行了10分钟的灌注与修改Krebs-Henseleit解决方案，15分钟的常温全脑缺血，再灌注15分钟。缺血前Langendorff期进行IP，其中6只心脏缺血2 min，再灌注8 min（IP 2组），6只心脏缺血5 min，再灌注5 min（IP 5组）。结果：缺血预处理5 min可明显改善缺血后心功能，缺血后24 h内心肌组织总肌酸激酶漏出量、cGMP漏出量及心肌含水率均显著高于缺血前（P < 0. 05），缺血后24 h内心肌组织总肌酸激酶漏出量、cGMP漏出量及心肌含水率均显著高于缺血前（P < 0. 05）。IP 5组的心输出量恢复百分比显著大于对照组（分别为88.8% ± 2.8%和66.7% ± 4.3%，平均值± SEM，p < 0.01）。各组间冠状窦血流恢复百分比、心率和心肌含水率无显著差异。IP后cGMP和肌酸激酶漏出量与对照组相比无显著性差异。但缺血15 min后，IP 5的cGMP漏出量明显低于其他各组（p= NS）。结论：IP 5分钟对心肌缺血再灌注损伤具有保护作用。环GMP可能在这种作用中发挥作用。

BACKGROUND/AIMS : Ischemic preconditioning (IP) has been suggested to protect the heart against ischemic and reperfusion injury. However, the mechanism of this phenomenon remains unknown. We thus examined the myocardial protective effect of IP and its relation to cGMP in the isolated perfused working heart model.METHODS : Eighteen hearts from male Wister rats were placed in the Langendorff circuit and subjected to 10 minutes of perfusion with a modified Krebs-Henseleit solution, 15 minutes of normothermic global ischemia, and 15 minutes of reperfusion. IP was performed in the pre-ischemic Langendorff period with 2 minutes' global ischemia and 8 minutes' reperfusion in six hearts (IP 2 group), 5 minutes' ischemia and 5 minutes' reperfusion in six hearts (IP 5 group). The other six hearts (control) were perfused without IP.Functional recovery, total creatin kinase leakage, cGMP leakage and myocardial water ratio were compared among the groups using ANOVA and Bonferroni/Dunn test.RESULTS : Five minutes of IP significantly improved post-ischemic cardiac function. Percent recovery of cardiac output in IP 5 was significantly greater than in control group (88.8% ± 2.8% versus 66.7% ± 4.3%, respectively, mean ± SEM, p < 0.01). There was no significant difference in percent recovery of coronary sinus flow, heart rate, and myocardial water ratio among the groups. After IP, there was no significant difference in cGMP and creatin kinase leakage compared with control group. However, cGMP leakage in IP 5 after 15 minutes' ischemia tended to be lower than other groups (p= NS).CONCLUSION : These data suggest that 5 minutes of IP has myocardial protective effect against ischemic and reperfusion injury. Cyclic GMP may play a role in this effect.