INHIBITION OF LIPOXYGENASE AND CYCLOOXYGENASE AUGMENTS CARDIAC INJURYBY H2O2

The role of arachidonic acid metabolites in the cardiac effects of tox ic oxygen metabolites (TOM) was investigated in buffer-perfused rat he arts (Langendorff model). Hydrogen peroxide (H2O2,200 muM) was given f or 10 min to generate TOM, followed by 30 min recovery. H2O2 reduced l eft 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 diet hylcarbamazine, in addition to H2O2, augmented the decrease of LVDP an d 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 drug s. Control perfusion with drugs alone did not influence cardiac functi on. In conclusion, inhibition of lipoxygenase and cyclooxygenase augme nted the depression of cardiac function induced by TOM. Leukotrienes a nd prostanoids appear to be protective against H2O2-induced cardiac in jury.