Fukuda H, Sawa Y, Kadoba K, Taniguchi K, Shimazaki Y, Matsuda H
First Department of Surgery, Osaka University School of Medicine, Japan.
Circulation. 1995 Nov 1;92(9 Suppl):II413-6. doi: 10.1161/01.cir.92.9.413.
Nitric oxide (NO) derived from the endothelial cell has been identified as a constitutive chemical mediator that regulates the function of the endothelial cell in association with neutrophil (PMN) adhesion and activation. However, its role in the pathogenesis of myocardial reperfusion injury is not clear.
Fifteen isolated rat hearts were perfused with modified Krebs-Henseleit solution and subjected to 20 minutes of global and normothermic ischemia. Then the hearts were reperfused for 45 minutes with different protocols: the control (C) group was reperfused without PMNs, the P group was reperfused with PMNs, and the N group was reperfused with PMNs and nitroprusside (10(-5) mol/L). The ozone chemiluminescence method was used for direct measurement of NO in the coronary effluent during reperfusion. NO in the coronary effluent in the C group decreased at reperfusion after normoxic perfusion, and this decrease in NO continued for the first 15 minutes of reperfusion. Percentage recovery of left ventricular developed pressure and coronary flow was significantly lower in the P group than that in the N group. Also, the N group had a significantly lesser Luminol-elicited chemiluminescence of the coronary effluent and ratio of PMN adherence to myocardial vasculature compared with the P group.
This study demonstrated directly the decrease in NO production during reperfusion and showed that supplement of NO with NO donor attenuated the injury in which PMNs were involved. The results suggest that NO plays a significant role in reperfusion injury and that supplement of NO during reperfusion appears to be useful to attenuate this injury.
来源于内皮细胞的一氧化氮（NO）已被确认为一种内源性化学介质，它与中性粒细胞（PMN）的黏附和激活相关，调节内皮细胞的功能。然而，其在心肌再灌注损伤发病机制中的作用尚不清楚。
15只离体大鼠心脏用改良的克雷布斯 - 亨塞尔特溶液灌注，进行20分钟的全心常温缺血。然后采用不同方案进行45分钟的再灌注：对照组（C组）在无PMN的情况下再灌注，P组在有PMN的情况下再灌注，N组在有PMN和硝普钠（10⁻⁵mol/L）的情况下再灌注。采用臭氧化学发光法直接测定再灌注期间冠状动脉流出液中的NO。C组在常氧灌注后再灌注时冠状动脉流出液中的NO降低，且这种NO降低在再灌注的前15分钟持续存在。P组左心室舒张末压和冠状动脉血流量的恢复百分比显著低于N组。此外，与P组相比，N组冠状动脉流出液的鲁米诺诱导化学发光以及PMN对心肌血管系统的黏附率显著降低。
本研究直接证明了再灌注期间NO生成减少，并表明用NO供体补充NO可减轻涉及PMN的损伤。结果提示NO在再灌注损伤中起重要作用，且再灌注期间补充NO似乎有助于减轻这种损伤。
