Tsao P S, Ma X L, Lefer A M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Am Heart J. 1992 Jun;123(6):1464-71. doi: 10.1016/0002-8703(92)90796-x.
Endothelial dysfunction, as evidenced by decreased stimulated release of endothelium-derived relaxing factor (EDRF), occurs after reperfusion of the ischemic myocardium. To better understand this endothelial dysfunction, isolated cat hearts were perfused under constant flow by the Langendorff procedure with Krebs-Henseleit solution devoid of blood cells. Following global ischemia (90 minutes) and reperfusion (20 minutes), coronary vasorelaxation to the endothelium-dependent vasodilator acetylcholine (ACh) was 70 +/- 3% of initial values (p less than 0.01) compared with 90 +/- 4% in nonischemic control perfused hearts. No decrement occurred in response to the endothelium-independent vasodilator nitroglycerin (NTG). Coronary artery rings isolated from the ischemic left circumflex coronary artery showed a similar degree of endothelial dysfunction to ACh, with normal relaxation in response to NaNO2. Autologous cat neutrophils (100 million cells), activated with 100 nmol/L f-met-leu-phe infused into the heart directly before and throughout reperfusion, resulted in a further decrement in ACh-induced vasodilation, to 55 +/- 5% of initial response, with no effect on NTG-induced vasodilation. Similar results were obtained with coronary artery rings isolated from perfused cat hearts and exposed to neutrophils. This neutrophil-enhanced endothelial dysfunction was inhibited by human superoxide dismutase as well as by an antibody to the adherence glycoprotein complex CD-18 (i.e., MAbR 15.7). Therefore endothelial dysfunction occurs initially upon reperfusion of the previously ischemic heart and is aggravated by superoxide radicals produced by activated neutrophils.
内皮功能障碍表现为内皮源性舒张因子（EDRF）刺激释放减少，发生于缺血心肌再灌注后。为更好地理解这种内皮功能障碍，采用Langendorff灌流法，用不含血细胞的Krebs-Henseleit溶液以恒流灌注离体猫心。在全心缺血90分钟及再灌注20分钟后，与非缺血对照灌流心脏中90±4%相比，对内皮依赖性血管扩张剂乙酰胆碱（ACh）的冠状动脉舒张作用为初始值的70±3%（p<0.01）。对非内皮依赖性血管扩张剂硝酸甘油（NTG）的反应未出现下降。从缺血的左旋冠状动脉分离出的冠状动脉环对ACh显示出相似程度的内皮功能障碍，对NaNO2反应正常。在再灌注前及整个再灌注过程中直接向心脏注入1亿个用100 nmol/L f-甲硫-亮-苯丙氨酸激活的自体猫中性粒细胞，导致ACh诱导的血管舒张进一步下降至初始反应的55±5%，对NTG诱导的血管舒张无影响。从灌流猫心分离并暴露于中性粒细胞的冠状动脉环也得到了类似结果。这种中性粒细胞增强的内皮功能障碍被人超氧化物歧化酶以及抗黏附糖蛋白复合物CD-18的抗体（即MAbR 15.7）所抑制。因此，内皮功能障碍最初发生于先前缺血心脏的再灌注时，并被激活的中性粒细胞产生的超氧阴离子自由基加重。
