Abstract 16206: Chronic Treatment with Long Acting Phosphodiesterase-5 Inhibitor Tadalafil Protects Against Diastolic Dysfunction in Type 1 Diabetic Cardiomyopathy
Background: Diabetic patients exhibit generalized endothelial and cardiac dysfunction with decreased nitric oxide (NO) production and bioavailability. Since phosphodiesterase-5 (PDE-5) inhibitors generate NO and protect against ischemia/reperfusion (I/R) injury, we tested the hypothesis whether chronic treatment with long acting PDE-5 inhibitor tadalafil (TAD) could improve diastolic dysfunction associated with streptozotocin (STZ)-induced Type 1 diabetic cardiomyopathy.
Methods and Results: Adult male CF-1 mice (n=6/group) were randomized to receive: DMSO (10%, 0.2 ml, i.p.), TAD (1 mg/kg, i.p for 28 days), STZ (150 mg/kg, i.p.) or STZ+TAD (1 mg/kg, i.p for 28 days). The mice were subjected to 30 min regional ischemia followed by 60 min reperfusion after 28 days. Infarct size was measured using computer morphometry of tetrazolium stained sections. Body weights and fasting blood glucose levels were monitored weekly. Cardiac function was assessed by transthoracic echocardiography. As summarized in Table, body weights were decreased and fasting blood glucose levels were increased significantly in the STZ-treated groups. The increased blood glucose levels were significantly reduced in the STZ+TAD group. STZ treatment caused a reduction in E/A ratio which was enhanced upon TAD treatment indicating an improvement in diastolic dysfunction, which often precedes impairments in systolic function in diabetic cardiomyopathy. Left ventricular systolic dysfunction was not evident among the groups during the 28 days period. Infarct size was significantly reduced in the TAD, STZ and STZ+TAD groups demonstrating cardioprotection against ischemia/reperfusion injury in STZ as well as TAD-treated diabetic and non-diabetic mice.
Conclusions: Chronic treatment with TAD could have beneficial effect in reducing blood glucose levels and in protection against diastolic dysfunction in Type I diabetic patients.
- © 2010 by American Heart Association, Inc.