ANTIOXIDANT AND OXIDATIVE STRESS CHANGES DURING HEART-FAILURE SUBSEQUENT TO MYOCARDIAL-INFARCTION IN RATS

Antioxidant enzyme activities and oxidative stress were evaluated in t he myocardium in relation to hemodynamic function subsequent to myocar dial infarction in rats. One week after the coronary ligation, the lef t ventricular peak systolic pressure, left ventricular end-diastolic p ressure, and aortic pressures remained near control values and there w ere no differences in lung and liver wet/dry weight ratios between exp erimental and control animals. In the 4-, 8-, and 16-week experimental animals, there was a progressive drop in left ventricular peak systol ic pressure and an increase in left ventricular end- diastolic pressur e. Aortic systolic pressure was depressed at 8 and 16 weeks. In myocar dial infarct rats, there was a significant increase in wet/dry weight ratio of lungs at 8 weeks and at 16 weeks; this ratio was increased fo r lungs as well as liver. Based on the hemodynamic data as well as oth er observations, animals in the 1-, 4-, 8-, and 16-week, groups were a rbitrarily categorized into nonfailure and mild, moderate, and severe failure stages, respectively. In the nonfailure stage, there was a mar ginal increase in superoxide dismutase, glutathione peroxidase, and ca talase activities as well as vitamin E levels. The redox state in thes e hearts, assessed by the reduced/oxidized glutathione ratio, was sign ificantly increased. Superoxide dismutase activity was unchanged in mi ld and moderate failure stages but significantly depressed at 16 weeks . Glutathione peroxidase and catalase activities showed progressive de creases through mild, moderate, and severe failure stages. Vitamin E l evels were significantly depressed at moderate and severe failure stag es. There was a progressive increase in lipid peroxidation at mild, mo derate, and severe stages of heart failure and the redox ratio was sig nificantly depressed in the severe failure stage. These data suggest t hat heart failure subsequent to myocardial infarction may be associate d with an antioxidant deficit as well as increased myocardial oxidativ e stress.