Valen G, Semb A G, Vaage J
Department of Surgery, University of Tromsø, Norway.
Free Radic Biol Med. 1993 Jul;15(1):27-35. doi: 10.1016/0891-5849(93)90122-b.
The role of arachidonic acid metabolites in the cardiac effects of toxic oxygen metabolites (TOM) was investigated in buffer-perfused rat hearts (Langendorff model). Hydrogen peroxide (H2O2, 200 microM) was given for 10 min to generate TOM, followed by 30 min recovery. H2O2 reduced left ventricular developed pressure (LVDP), increased left ventricular end-diastolic pressure (LVEDP), and increased coronary flow (CF). The hydroxyl radical scavenger thiourea inhibited the H2O2-induced effects. Perfusion with three lipoxygenase inhibitors, AA861, BWA4C, and diethylcarbamazine, in addition to H2O2, augmented the decrease of LVDP and the increase of LVEDP induced by H2O2. The cyclooxygenase inhibitor indomethacin had the same effects. The H2O2-induced increase in CF was not influenced by diethylcarbamazine, but inhibited by all other drugs. Control perfusion with drugs alone did not influence cardiac function. In conclusion, inhibition of lipoxygenase and cyclooxygenase augmented the depression of cardiac function induced by TOM. Leukotrienes and prostanoids appear to be protective against H2O2-induced cardiac injury.
在缓冲液灌注的大鼠心脏（Langendorff模型）中研究了花生四烯酸代谢产物在毒性氧代谢产物（TOM）心脏效应中的作用。给予过氧化氢（H2O2，200微摩尔）10分钟以产生TOM，随后恢复30分钟。H2O2降低左心室舒张末压（LVDP），增加左心室舒张末压（LVEDP），并增加冠状动脉流量（CF）。羟基自由基清除剂硫脲抑制H2O2诱导的效应。除H2O2外，用三种脂氧合酶抑制剂AA861、BWA4C和二乙氨基甲嗪灌注，增强了H2O2诱导的LVDP降低和LVEDP升高。环氧化酶抑制剂吲哚美辛具有相同的作用。H2O2诱导的CF增加不受二乙氨基甲嗪影响，但被所有其他药物抑制。单独用药物进行对照灌注不影响心脏功能。总之，抑制脂氧合酶和环氧化酶增强了TOM诱导的心脏功能抑制。白三烯和前列腺素似乎对H2O2诱导的心脏损伤具有保护作用。
