Pharmacological study on the derangements of myocardial cells induced by oxygen radicals, and protection from the derangements

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We found that H_2O_2 produces ischemia/reperfusion-like changes on the isolated rat heart in both mechanical and metabolic functions and lipid peroxidation, and that lidocain decreases the H_2O_2-induced damage. These results support our hypothesis that oxygen radicals produce ischemia/reperfusion damage, and that the anti-ischemic drug protects the myocardial damage induced by oxygen radicals. We also found that H_2O_2 produces cell damage in the presence of Fe^<2+> in the isolated cardiac cells. The H_2O_2-induced damage to the myocyte was protected by d-propranolol and K-7259, a novel derivative of dilazep. Next, we found that LPC produced ischemia/reperfusion-like damage to the isolated heart, and that d-propranolol and K-7259 attenuated the LPC-induced damage to the isolated haert. In the next experiments, we measured intraceullar Ca^<2+> concentration ([Ca^<2+>]_i) in the cardiac myocyte. LPC increased ([Ca^<2+>]_i) markedly and dilazep and d-propranolol attenuated the LPC-induced increase in ([Ca^<2+>]_i). Next, we examined the effect of beta-adrenoceptor antagonists on the LPC-induced increase in ([Ca^<2+>]_i), and found that l- and d-propranolol, and l- and dpenbutolol were effective in attenuating the LPC-induced increased in ([Ca^<2+>]_i). Lastly, we examined the effect of LPC on the ion channel in the cardiac myocyte, and found that LPC increases the non-selective cation channel current through which Ca^<2+> can pass.These results suggst that oxygen radicals like hydrogen peroxide produces peroxidation of the phospholipids of the cardiac cell membrane, releasing LPC.LPC then increases ([Ca^<2+>]_i) through non-selective cation channel. d-Propranolol and K-7259, a derivative of dilazep, attenuated both H_2O_2-induced and LPC-induced damage to the cardiac myocyte.