sulindac and Cardiomyopathy--Hypertrophic

The aim of the present study was to investigate the cardioprotective activity of sulindac as an aldose reductase inhibitor in the development of cardiomyopathy by non-invasive techniques; M-mode and Doppler echocardiography. Diabetes was induced by streptozotocin (45 mg/kg, iv) in the Sprague-Dawley rats. Echocardiography, biochemical and histological studies were carried out in normal control, diabetic untreated, diabetic vehicle (sodium carboxy methyl cellulose, 1%, po) and sulindac (6 mg/kg and 20 mg/kg, po) treated animals at varying time intervals. In the diabetic untreated and vehicle treated rats at 12 weeks after induction of diabetes, there was a significant decrease in the E-wave, an increase in the A-wave and corresponding decrease in the E/A ratio was observed. Significant decrease in the Eat was found after 12 weeks (P < 0.05). Whereas systolic function variables; ejection fraction and fractional shortening were significantly decreased (P < 0.05) after 12 weeks compared to their baseline data. In the sulindac treated animals, there were no significant alterations in the systolic and diastolic parameters were found throughout the study period. Myocardial fructose levels were significantly increased in the diabetic untreated animals compared to normal control rats (P < 0.05), whereas these were significantly decreased in the sulindac (6 mg/kg and 20 mg/kg) treated animals (301.11+/-37.98, 214.11+/-25.31, vs. 914.88+/-56.01 nmol/g) compared to diabetic vehicle treated group (P < 0.05). Extensive focal ischemic myocyte degeneration was observed in the diabetic untreated and vehicle treated rats, whereas in the sulindac (6 mg/kg) treated rats, minimal necrosis was found, with no evidence of necrosis in sulindac (20 mg/kg) group. Our results show for the first time that sulindac has a cardioprotective activity as this agent prevented the development of left ventricular dysfunction in STZ-induced diabetic rats in the 12-week chronic study.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Blood Proteins; Body Weight; Carboxymethylcellulose Sodium; Cardiomyopathy, Hypertrophic; Cholesterol; Diabetes Mellitus, Experimental; Echocardiography, Doppler; Fructose; Heart; Male; Myocardium; Rats; Rats, Sprague-Dawley; Sulindac; Triglycerides; Ventricular Dysfunction, Left