Effects of acidic reperfusion on ischemia-reperfusion injury in isolated rat teart: role of PDK/Akt signaling pathway

Abstract

Objective To investigate the effects of acidic reperfusion on ischemia-reperfusion injury in isolated rat heart and the role of PI3K/Akt signaling pathway. Methods Seventy adult SD rats weighing 450-550 g were randomly divided into 7 groups （ n = 10 each） ： group Ⅰischemia-reperfusion injury （I/R） ; group Ⅱ ischemic post conditioning （IPC） ; group Ⅲ acidic reperfusion （H＋ ） ; group Ⅳ ischemic postconditioning ＋ alkalotic repeffusion （IPC ＋ OH^- ）; group Ⅴ alkalotic repeffusion （OH-）; group Ⅵ acidic reperfusion ＋ wortmannin （H^＋ ＋ wort） and group Ⅶ wortmannin （wort）. The animals were anesthetized with intraperitoneal （IP） urethane. Their chests were opened and hearts were excised and passively per[used in a Langendorff apparatus with Krebs- Henseleit buffer （KHB） saturated with 95 % O2-5 % O2 at 37℃ . The isolated hearts were made globally ischemie for 30 min followed by 120 min reperfusion. Group Ⅱ（IPC） was subjected to 6 cycles of 15 min reperfusion and 15 min ischemia at the beginning of reperfusion. In group H^＋ and OH^- （group Ⅲ , Ⅴ ） the isolated hearts were perfused with KHB of pH 6.9 and 7.8 for 3 min respectively at the beginning of reperfusion. In group IPC ＋ OH^- （ Ⅳ ） the isolated hearts were perfused with KHB of pH 7. 8 for 3 rain followed by IPC. In group H^＋ ＋ wort and wort （ Ⅵ ,Ⅶ ） the isolated hearts were perfused with wortmannin 100 nmol/L in KHB of pH 6.9 and 7.4 for 3 min respectively at the beginning of reperfusion. LVEDP and ±dp/dtmax were measured before ischemia and at 30 min of reperfusion. Coronary effluent was collected for determination of NO concentration at 30 rain of reperfusion. Infart size was measured at 120 min of reperfusion. Results The LVEDP was decreased, ＋ dp/dtmax was increased, the infarct size was smaller and the NO concentration in coronary effluent was higher in group IPO and H^＋ compared with group I/R. Wortmannin abolished the protective effect of acidic reperfusion on isolated rat heart. Conclusion PI3K/Akt signaling pathway may be involved in the protective effects of acidic reperfusion on myocardium against ischemia-reperfusion injury. Key words: Acidosis ; Myocardial reperfusion injury ; 1-Phosphatidylinositol 3-kinase ; Protein- serine-threonine kinases