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

近年来，心脏手术中的再灌注损伤，特别是氧自由基损伤已引起人们的关注。但其机制尚未阐明。作为再灌注损伤的来源之一，我们注意到多形核白细胞（PMNs）的呼吸爆发产生大量的自由基。我们首先观察了体外循环中中性粒细胞化学发光（ChL）活性的变化，以探讨中性粒细胞是否容易发生呼吸爆发。再灌注30分钟后活性增加1.82倍（p<0.05）。提示再灌注后易发生呼吸爆发，即参与再灌注损伤。接下来，我们研究了在犬交叉循环方法下，去除再灌注血中的白细胞是否会降低非再灌注损伤的程度。去白细胞血再灌注组左室功能恢复较好，过氧化产物减少，CPK-MB释放减少。电镜下可见细胞外水肿加重，内皮细胞上粘附有较多的片状物，内皮细胞损伤严重，线粒体损伤较多。与此相反，在用全血再灌注的组中，内皮和线粒体损伤较少。此外，我们试图检查在管理组的内皮细胞和线粒体损伤的超氧化物歧化酶，作为一种自由基清除剂，在心脏骤停。这一组显示出与全血组几乎相同的内皮和线粒体损伤。这些结果提示，PMN在再灌注损伤中起一定作用，再灌注后即刻自由基引起的内皮细胞损伤是PMN再灌注损伤的触发因素。在此之后，再灌注后的内皮变化将需要更深入的研究。

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.