Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure.
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).


RESULTS
Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, rat ghrelin (100 microg/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.
Nagaya
N
N
Department of Internal Medicine, National Cardiovascular Center, Fujishirodai, Suita, Osaka, Japan. nagayann@hsp.ncvc.go.jp
Uematsu
M
M
Kojima
M
M
Ikeda
Y
Y
Yoshihara
F
F
Shimizu
W
W
Hosoda
H
H
Hirota
Y
Y
Ishida
H
H
Mori
H
H
Kangawa
K
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000517:prevention & control*; D002469:Cell Separation; D002908:Chronic Disease; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004452:Echocardiography; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D036361:Peptide Hormones; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*
D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone