Research for elucidating the mechanism of ischemia-reperfusion injury at cardiopulumonary bypass, and taking countermeasures against it (1990)

近年来，心脏外科手术中的再灌注损伤，尤其是氧源性自由基的再灌注损伤已引起人们的关注。但其机制尚未明确。作为再灌注损伤的来源之一，我们注意到多形核白细胞（PMNs）的呼吸爆发，它产生大量自由基。首先观察体外循环过程中PMNs化学发光（ChL）活性的变化，探讨PMNs是否容易发生呼吸爆发。再灌注30min后活性增加1.82倍（p< 0.05）。提示PMNs在再灌注后易发生呼吸爆发，提示PMNs参与再灌注损伤。接下来，我们研究了再香血的白细胞消耗是否会降低非犬交叉循环法下的再灌注损伤程度。白细胞再灌注组左心室功能恢复较好，过氧化产物较少，CPK-MB释放较少。病理电镜显示细胞外水肿较多，内皮血小板粘附较多，内皮细胞损伤较多，线粒体损伤较多。与该组相比，全血再灌注组内皮细胞和线粒体损伤较小。此外，我们试图检查在心脏骤停期间使用超氧化物歧化酶作为自由基清除剂的组的内皮和线粒体损伤。这一组表现出与全血组相同的内皮和线粒体损伤。上述结果提示，PMNs在再灌注损伤中起一定作用，再灌注后自由基源性内皮损伤可触发后续PMNs再灌注损伤。在此之后，需要进一步观察再灌注后内皮细胞的变化。

Recently the reperfusion injury, especially by oxygen-derived free radicals, has been noticed in cardiac surgery. But the mechanism has not been clarified. As one of sources of reperfusion injury, we noticed respiratory burst of polymorphonuclear leukocytes (PMNs), which produce a lot of free radicals. At first we looked over the change of chemiluminescence (ChL) activity in PMNs during cardiopulmonary bypass to investigate whether respiratory burst of PMNs would be apt to occur. The activity increased 1.82 times (p<.05) 30 min. after reperfusion. This result pointed out that the respiratory burst of PMNs would be liable to occur after reperfusion, namely it suggested that PMNs would take a part in reperfusion injury. Next we investigated whether leukocyte depletion of reperfuming blood would reduce the degree of reperfusion injury of not under the canine cross circulation method. The group reperfused with leukocyte depleted blood showed better recovery of left ventricle function, less peroxidation products, and less CPK-MB release. Pathologically, electron micrograph showed more extracellular edema, much platblete adhesion on the endothelium, much endothelial cell damage, and more mitochondrial damage in this group. In contrast to this group, in the group reperfused with whole blood less endothelial and mitochondrial damage. Further we tried to examine endothelial and mitochondrial damage in the group in administration of superoxide dismutase, as a free radical scavenger, during heart arrest. This group showed much the same endothelial and mitochondrial damage as the whole blood group. These results suggest that PMNs would take some parts in reperfusion injury, and free radical derived endothelial damage just after reperfusion would occur as the trigger of the foll owing PMNs derived reperfusion injury. After this, the endothelial change after reperfusion will be required on closer investigation.