McDonagh P F, Roberts D J
Circ Res. 1986 Jan;58(1):127-36. doi: 10.1161/01.res.58.1.127.
Coronary microvascular damage appears to play a role in reperfusion injury after myocardial ischemia. This study was designed to afford direct viewing of the effects of myocardial ischemia-reperfusion on the coronary microcirculation and to determine whether pretreatment with the calcium blocker nisoldipine would attenuate any microvascular damage during reperfusion. Four groups of isolated rat hearts were perfused with a solution that contained red cells and fluorescent albumin, but was essentially free of platelets and leukocytes. Group I served as a nonischemic control. Group II hearts were subjected to 30 minutes of no-flow ischemia followed by reperfusion. Group III hearts were pretreated with nisoldipine (1 microgram/min) for 5 minutes before ischemia, and group IV hearts were treated with nitroglycerin (93 micrograms/min) before and after ischemia to mimic the vasodilation caused by nisoldipine. Perfused coronary capillarity and transcoronary extravasation of plasma albumin were measured by direct visualization techniques before and after ischemia. For group I, there was no significant change in coronary resistance, perfused capillarity, or transcoronary extravasation with time. For both groups II and IV, ischemia-reperfusion caused no increase in coronary resistance, but a significant decrease in perfused capillarity and a marked increase in transcoronary extravasation of fluorescent albumin (P less than 0.05). The nisoldipine group (group III) demonstrated a similar decrease in perfused capillarity but no increase in protein extravasation during reperfusion. These results indicate that, in the heart, platelets and/or leukocytes are not absolutely necessary to induce either the no-reflow phenomenon or the permeability damage observed during reperfusion after ischemia. The protective effect of treatment with nisoldipine appeared to be independent of vasodilation. We speculate that this calcium blocker reduced endothelial uptake of calcium during reperfusion, preventing endothelial deformation and formation of interendothelial gaps.
冠状动脉微血管损伤似乎在心肌缺血后的再灌注损伤中起作用。本研究旨在直接观察心肌缺血-再灌注对冠状动脉微循环的影响，并确定钙通道阻滞剂尼索地平预处理是否会减轻再灌注期间的任何微血管损伤。四组离体大鼠心脏用含有红细胞和荧光白蛋白但基本不含血小板和白细胞的溶液灌注。第一组作为非缺血对照组。第二组心脏进行30分钟无血流缺血后再灌注。第三组心脏在缺血前用尼索地平（1微克/分钟）预处理5分钟，第四组心脏在缺血前后用硝酸甘油（93微克/分钟）处理以模拟尼索地平引起的血管舒张。在缺血前后通过直接可视化技术测量灌注的冠状动脉毛细血管和血浆白蛋白的冠状动脉外渗。对于第一组，冠状动脉阻力、灌注的毛细血管或冠状动脉外渗随时间没有显著变化。对于第二组和第四组，缺血-再灌注均未导致冠状动脉阻力增加，但灌注的毛细血管显著减少，荧光白蛋白的冠状动脉外渗显著增加（P<0.05）。尼索地平组（第三组）在再灌注期间表现出类似的灌注毛细血管减少，但蛋白质外渗没有增加。这些结果表明，在心脏中，血小板和/或白细胞对于诱导缺血后再灌注期间观察到的无复流现象或通透性损伤并非绝对必要。尼索地平治疗的保护作用似乎与血管舒张无关。我们推测这种钙通道阻滞剂减少了再灌注期间内皮细胞对钙的摄取，防止了内皮细胞变形和内皮细胞间隙的形成。
