EFFECTS OF A NOVEL LOW-MOLECULAR-WEIGHT ANTIOXIDANT ON CARDIAC INJURY-INDUCED BY HYDROGEN-PEROXIDE

H290/51, an indenoindole derivative, is a novel low-molecular weight ( 287.8) inhibitor of lipid peroxidation. Its effect on cardiac injury i nduced by exogenous reactive oxygen intermediates (ROI) was investigat ed. ROI were generated by adding H2O2 (180 mu M) to the perfusate of i solated rat hearts (Langendorff model, n = 9) for 10 min. H2O2 reduced left ventricular developed pressure (LVDP = left ventricular systolic pressure - left ventricular end-diastolic pressure) from 90 +/- 6 to a minimum of 25 +/- 2 mmHg (mean +/- SEM) after 10 min (p < 0.001), el evated left ventricular end-diastolic pressure (LVEDP) from 0 to 32 +/ - 7 mmHg after 20 min (p < 0.0001), and increased coronary flow (CF). Lactate dehydrogenase (LDH) release in the coronary effluent and thiob arbituric acid-reactive substances (TEARS) in cardiac tissue increased (TEARS from 0.6 +/- 0.04 to 3.1 +/- 0.4 nmol/g tissue after 10 min of H2O2 administration, p < 0.001). Addition of H290/51 (1 mu M, n = 12) from the start of H2O2 exposure, attenuated the H2O2-induced increase of LVEDP (9 +/- 3 mmHg at 20 min, p < 0.006) and reduced the release of LDH (p < 0.02 at 30 min). LVDP was not significantly influenced. Th e increase of TEARS was abolished by H290/51 (p < 0.001). In conclusio n, H290/51 inhibited lipid peroxidation, and attenuated functional and biochemical injury induced by H2O2 exposure.