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，尤其是氧自由基引起的再灌注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(PMN)呼吸爆发，产生大量的自由基。首先，我们观察了体外循环期间中性粒细胞化学发光(ChL)活性的变化，以探讨PMN是否容易发生呼吸爆发。30min酶活提高1.82倍(p&lt；0.05)。再灌流后。提示中性粒细胞在再灌注后易发生呼吸爆发，提示中性粒细胞可能参与了再灌注损伤。接下来，我们在犬交叉循环的方法下，研究去白细胞再灌流血是否能减轻非再灌流损伤的程度。去白细胞再灌注组的左心功能恢复较好，过氧化产物较少，CPK-MB释放较少。病理组织学表现为细胞外水肿较多，内皮细胞黏附较多，内皮细胞损伤较多，线粒体损伤较多。与此组相比，全血再灌注组血管内皮细胞和线粒体损伤较轻。此外，我们试图检测在心脏骤停期间给予超氧化物歧化酶作为自由基清除剂的组内皮细胞和线粒体的损伤。这组人表现出与全血组大致相同的内皮和线粒体损伤。提示中性粒细胞在再灌注损伤中起一定作用，再灌注后即发生自由基源性内皮损伤是中性粒细胞再灌注损伤的触发因素。在此之后，再灌注后血管内皮细胞的变化将需要进一步的研究。

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.