No effects of human ghrelin on cardiac function despite profound effects on body composition in a rat model of heart failure.
BACKGROUND
Ghrelin, was observed to have treatment-potential for severe chronic heart failure (CHF) and cardiac cachexia based on anti-cachectic and cardio-protective effects.


METHODS
We performed two studies to assess the effects of human ghrelin on food intake, body weight and body composition, as well as heart function in a rat model of CHF. Study-1 (50 or 500 nmole/kg/d ghrelin by pump infusion) was focused on food intake and body composition, study-2 (50 or 100 nmole/kg/d ghrelin by subcutaneous injection (3-times daily) was focused on heart function due to a lack of cardiac effects observed in study-1. In both studies, myocardial infarction was induced by LAD ligation. On day 28 after surgery, rats were randomized and treated with ghrelin or placebo for 4 weeks. Food intake (study-1), body composition (NMR) cardiac function (echocardiography and invasive hemodynamics (study-2 only) were assessed.


RESULTS
In study-1, CHF rats treated with high dose ghrelin showed an increase in body weight (+25%, p<0.001), lean mass (+16%, p<0.01) and fat mass (+17%, p=0.001) vs placebo. In study-2, CHF rats treated with both low- and high dose ghrelin showed an increase in body weight (both +18%, p</=0.001), lean mass (both +25%, p<0.001) and fat mass (50 nmole/kg/d: +43%, p<0.05; 100 nmole/kg/d: +45%, p<0.01) vs placebo. However, no beneficial effect of ghrelin treatment on left ventricular ejection fraction or change of LV diameters was observed in either study.


CONCLUSIONS
Ghrelin treatment results in dose-dependent beneficial effects on body weight and body composition, but does not improve cardiac function.
Akashi
Yoshihiro J
YJ
Division of Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany.
Palus
Sandra
S
Datta
Rakesh
R
Halem
Heather
H
Taylor
John E
JE
Thoene-Reineke
Christa
C
Dong
Jesse
J
Thum
Thomas
T
Culler
Michael D
MD
Anker
Stefan D
SD
Springer
Jochen
J
D000704:Analysis of Variance; D000818:Animals; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004435:Eating; D004452:Echocardiography; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D054439:Ghrelin