Circulation. 2001;104:1430-1435
doi: 10.1161/hc3601.095575
doi: 10.1161/hc3601.095575
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(Circulation. 2001;104:1430.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure
From the Department of Internal Medicine, National Cardiovascular Center (N.N., W.S.), the Department of Internal Medicine, Osaka Seamen’s Insurance Hospital (M.U.), the Department of Biochemistry, National Cardiovascular Center Research Institute (M.K., F.Y., H.H., K.K.), the Department of Pathology, National Cardiovascular Center (Y.I.), and the Department of Cardiac Physiology, National Cardiovascular Center Research Institute (H.M.), Osaka, and the Department of Physiology and Research Center for Genetic Engineering and Cell Transplantation, Tokai University, Kanagawa (Y.H., H.I.), Japan.
Reprint requests to Noritoshi Nagaya, MD, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail nagayann{at}hsp.ncvc.go.jp
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/dtmax (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.
Key Words: heart failure • hormones • growth substances • nutrition
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