Abstract 11307: A Direct Renin Inhibitor Significantly Improves Survival and Cardiac Remodeling after Myocardial Infarction in the Condition of Renal Failure
Background: The activity of renin angiotensin system (RAS) is known to be a key factor in the pathophysiology of heart failure and renal disease. Aliskiren, a direct renin inhibitor (DRI), is broadly used as an anti-hypertension drug. However, the cardioprotective effect of aliskiren has not yet been elucidated in the condition of renal failure.
Hypothesis: We assessed the hypothesis that a renin inhibition could attenuate LV remodeling after myocardial infarction in the condition of renal failure.
Methods: The murine model of subtotal nephrectomy was made by a two-step surgical procedure. Four weeks after nephrectomy, myocardial ischemia was induced by the left anterior descending coronary artery ligation and this continued for 28 days. The animals were assigned randomly into four treatment groups, and were administrated a subcutaneous injection of aliskiren (low dose 2.5mg/kg, or high dose 25mg/kg), hydralazine hydrochloride (30mg/kg), or vehicle.
Results: Blood pressure decline was observed in the group of high-dose aliskiren, while the low-dose aliskiren did not suppress blood pressure. The hydralazine declined blood pressure; the effect was comparable to high-dose aliskiren treatment. Although many mice in the vehicle-treated group died during this observation period (77.3% survival, n=23), aliskiren treatment significantly improved the survival rate (low-dose, 100% (n=19); high dose, 92.3% (n=26), p<0.05 vs. vehicle). However, hydralazine treated mice showed comparable survival rate (76.9%, n=13) to vehicle treated mice. Echocardiogram demonstrated that both doses of aliskiren treatment significantly improved left ventricular ejection fraction (high dose, 65.4±2.4%, low dose 54.1±6.1%, p<0.05 vs. vehicle) in comparison to the vehicle-treated group (36.4±2.2%). Pathologically, high-dose aliskiren significantly suppressed the infarction-induced LV thinning (0.75±0.1 vs. 0.43±0.1 mm) and enlarged LV circumference (8.9±0.6 vs. 12.1±0.9 mm) in comparison to the vehicle treated group.
Conclusions: Aliskiren offers significant potential for survival and cardiac protection after myocardial infarction in the condition of renal failure.
- © 2010 by American Heart Association, Inc.