Quillen J E, Sellke F W, Brooks L A, Harrison D G
University of Iowa, Cardiovascular Center, Iowa City.
Circulation. 1990 Aug;82(2):586-94. doi: 10.1161/01.cir.82.2.586.
We examined the effects of ischemia with and without reperfusion on endothelium-dependent and -independent vascular relaxation in both conduit and resistance coronary arteries. Studies were performed on dogs under control conditions (n = 13) or after 1 hour of circumflex coronary artery occlusion with (n = 10) or without (n = 8) 1 hour of reperfusion. Rings of obtuse marginal branches of the left circumflex coronary artery (conduit arteries) were studied in organ chambers. Coronary microvessels (110-220-microns diameter) were studied in a pressurized state with an in vitro microvessel imaging apparatus. Relaxation was evaluated after preconstriction with prostaglandin F2 alpha and U46619 (a thromboxane A2 analogue) in conduit and resistance vessels, respectively. Conduit vessel function was not altered by ischemia with or without reperfusion. Endothelium-dependent microvascular relaxation was depressed in response to acetylcholine, ADP, and calcium ionophore A23187 after ischemia with reperfusion compared with control relaxation (ED50 as -log[M]: 6.0 +/- 0.2 [p less than 0.05], 5.1 +/- 0.4 [p less than 0.05], and 5.8 +/- 0.1 versus 6.8 +/- 0.2, 6.8 +/- 0.2, and 6.6 +/- 0.2, respectively). Ischemia without reperfusion modestly altered microvascular endothelium-dependent relaxation. Microvascular relaxation to nitroglycerin was not altered by ischemia with reperfusion. We conclude that 1) endothelium-dependent relaxation in large epicardial coronary arteries is relatively refractory to ischemia with or without reperfusion, 2) ischemia alone produces mild alterations of coronary microvascular reactivity, 3) ischemia followed by reperfusion produces a marked and selective impairment of endothelium-dependent responses in the coronary microcirculation.
我们研究了有无再灌注的缺血对冠状动脉主干和阻力血管中内皮依赖性及非内皮依赖性血管舒张的影响。在对照条件下（n = 13）或左旋冠状动脉闭塞1小时后（n = 10，有1小时再灌注；n = 8，无再灌注）对犬进行研究。在器官浴槽中研究左旋冠状动脉钝缘支（冠状动脉主干）的血管环。使用体外微血管成像设备在加压状态下研究冠状动脉微血管（直径110 - 220微米）。分别用前列腺素F2α和U46619（一种血栓素A2类似物）预收缩后，评估冠状动脉主干和阻力血管的舒张情况。有无再灌注的缺血均未改变冠状动脉主干血管的功能。与对照舒张相比，再灌注缺血后，内皮依赖性微血管舒张对乙酰胆碱、ADP和钙离子载体A23187的反应降低（ED50以-log[M]表示：分别为6.0 ± 0.2 [p < 0.05]、5.1 ± 0.4 [p < 0.05]、5.8 ± 0.1，而对照分别为6.8 ± 0.2、6.8 ± 0.2、6.6 ± 0.2）。无再灌注的缺血轻微改变微血管内皮依赖性舒张。再灌注缺血未改变微血管对硝酸甘油的舒张反应。我们得出结论：1）有无再灌注的缺血对大的心外膜冠状动脉中的内皮依赖性舒张相对不敏感；2）单独缺血对冠状动脉微血管反应性产生轻微改变；3）缺血后再灌注导致冠状动脉微循环中内皮依赖性反应显著且选择性受损。
