Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure

Abstract

Background — Ghrelin is a novel growth hormone (GH)–releasing peptide that may also induce vasodilation and stimulate feeding through GH-independent mechanisms. We investigated whether ghrelin improves left ventricular (LV) dysfunction and attenuates cardiac cachexia in rats with chronic heart failure (CHF). Methods and Results — Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, rat ghrelin (100 μg/kg SC BID) or saline was administered for 3 weeks. Echocardiography and cardiac catheterization were performed. Serum GH and insulin-like growth factor-1 were significantly higher in both CHF and sham rats treated with ghrelin than in those given placebo ( P <0.05 for both). CHF rats given placebo showed an impaired increase in body weight compared with sham rats given placebo ( P <0.05). CHF rats treated with ghrelin, however, showed a significantly greater increase in body weight than those given placebo (+10% versus +3%, P <0.05). They showed significantly higher cardiac output (315±49 versus 266±31 mL · min −1 · kg −1 , P <0.05) and LV dP/dt max (5738±908 versus 4363±973 mm Hg/s, P <0.05) than CHF rats given placebo. Ghrelin increased diastolic thickness of the noninfarcted posterior wall, inhibited LV enlargement, and increased LV fractional shortening in CHF rats (from 15±3% to 19±3%, P <0.05). Conclusions — Chronic subcutaneous administration of ghrelin improved LV dysfunction and attenuated the development of LV remodeling and cardiac cachexia in rats with CHF.