POLYMORPHONUCLEAR LEUKOCYTES-INDUCED INJURY IN HYPOXIC CARDIAC MYOCYTES

Growing evidence suggests that free radicals derived from polymorphonu clear leukocytes (PMNs) play an important role in myocardial ischemia- reperfusion injury. To elucidate the cellular mechanism by which activ ated PMNs exacerbate ischemic myocardial damage, we investigated the e xtent of cell injury, assessed by the morphological deterioration, fre e radical generation, and lipid peroxidation in mouse embryo myocardia l cells coincubated with activated PMNs. The generation of PMN-derived free radicals was related to the extent of myocardial cell injury. Wh en myocardial cell sheets were subjected to hypoxia and glucose-free m edia, myocardial cells were injured (cristalysis in the mitochondria a nd disruption of the sarcolemma) after adding various PMN activators, and the injury extended to the adjacent cells. Chemiluminescent emissi on and production of thiobarbituric acid-reactive substances in the co incubated cells increased markedly compared with myocardial cells or P MNs alone. The augmented lipid peroxidation coincided with the progres sion of myocardial cell injury. Catalase inhibited the myocardial cell injury 52%, the chemiluminescence by 46%, and lipid peroxidation by 5 0%, whereas superoxide dismutase exhibited less pronounced inhibition. These results indicate that a chain reaction of lipid peroxidation in myocardial cells induced by PMN-derived free radicals closely correla tes with membrane damage and contributes to the propagation of irrever sible myocardial cell damage.