Donato Martín, D'Annunzio Verónica, Berg Gabriela, Gonzalez Germán, Schreier Laura, Morales Celina, Wikinski Regina L W, Gelpi Ricardo J
Institute of Cardiovascular Pathophysiology, Faculty of Medicine, University of Buenos Aires, Argentina.
J Cardiovasc Pharmacol. 2007 May;49(5):287-92. doi: 10.1097/FJC.0b013e31803c55fe.
The effect of ischemic postconditioning (Postcon) in hypercholesterolemic animals is unknown. The objectives were to determine if ischemic preconditioning (IPC) and Postcon reduce infarct size in hypercholesterolemic animals and to assess if A1 receptors and K+(ATP) channels are involved in Postcon mechanisms. Isolated rabbit hearts were perfused according to the Langendorff technique and subjected to 30 minutes of ischemia and 30 minutes of reperfusion (G1). In Group 2, IPC was performed (1 cycle of 5 minutes ischemia/reperfusion) before 30 minutes of ischemia. In Group 3 (G3), Postcon was performed (2 cycles of 30-second reperfusion/ischemia) after 30 minutes of ischemia. The G3 protocol was repeated in G4 and G5, but during Postcon, an A1 receptor blocker (DPCPX, 200 nM) and glybenclamide (K+(ATP), blocker, 0.3 microM) were administered, respectively. The G1 to G5 protocols were repeated in animals fed with an enriched cholesterol diet (1%) for 4 weeks (G6 to G10). The infarct size was measured by triphenyltetrazolium. The infarct size was 16.6 +/- 4.6% in G1 and 25.8 +/- 7.3% in G6, and IPC and Postcon reduced the infarct area in both normal and hypercholesterolemic animals (G2: 5.1 +/- 1.7% [P < 0.05] and G3: 5.4 +/- 0.9% [P < 0.05] in normal animals; G7: 4.1 +/- 1.6% [P < 0.05] and G8 4.8 +/- 0.9% [P < 0.05], in hypercholesterolemic animals). Both DPCPX and glybenclamide abolished the effect reached by Postcon. Thus, Postcon reduces infarct size in normal and hypercholesterolemic animals through the activation of A1 and K+(ATP) channels.
缺血后处理（Postcon）对高胆固醇血症动物的影响尚不清楚。本研究的目的是确定缺血预处理（IPC）和Postcon是否能减小高胆固醇血症动物的梗死面积，并评估A1受体和K⁺（ATP）通道是否参与Postcon机制。采用Langendorff技术对离体兔心进行灌注，使其经历30分钟缺血和30分钟再灌注（G1组）。在第2组中，在30分钟缺血前进行IPC（1个周期的5分钟缺血/再灌注）。在第3组（G3组）中，在30分钟缺血后进行Postcon（2个周期的30秒再灌注/缺血）。在G4组和G5组中重复G3组的方案，但在Postcon期间，分别给予A1受体阻滞剂（DPCPX，200 nM）和格列本脲（K⁺（ATP）阻滞剂，0.3 microM）。将G1至G5组的方案在喂食富含胆固醇饮食（1%）4周的动物中重复（G6至G10组）。用三苯基四氮唑测量梗死面积。G1组梗死面积为16.6±4.6%，G6组为25.8±7.3%，IPC和Postcon在正常和高胆固醇血症动物中均减小了梗死面积（正常动物中，G2组：5.1±1.7%[P<0.05]，G3组：5.4±0.9%[P<0.05]；高胆固醇血症动物中，G7组：4.1±1.6%[P<0.05]，G8组：4.8±0.9%[P<0.05]）。DPCPX和格列本脲均消除了Postcon所达到的效果。因此，Postcon通过激活A1和K⁺（ATP）通道减小正常和高胆固醇血症动物的梗死面积。
