Abstract | 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. CONCLUSION:
Ghrelin treatment results in dose-dependent beneficial effects on body weight and body composition, but does not improve cardiac function.
|
Authors | Yoshihiro J Akashi, Sandra Palus, Rakesh Datta, Heather Halem, John E Taylor, Christa Thoene-Reineke, Jesse Dong, Thomas Thum, Michael D Culler, Stefan D Anker, Jochen Springer |
Journal | International journal of cardiology
(Int J Cardiol)
Vol. 137
Issue 3
Pg. 267-75
(Nov 12 2009)
ISSN: 1874-1754 [Electronic] Netherlands |
PMID | 18723230
(Publication Type: Journal Article)
|
Chemical References |
|
Topics |
- Analysis of Variance
- Animals
- Body Composition
(drug effects)
- Body Weight
(drug effects)
- Disease Models, Animal
- Eating
- Echocardiography
- Ghrelin
(administration & dosage, pharmacology)
- Heart Failure
(drug therapy, physiopathology)
- Hemodynamics
- Humans
- Injections, Subcutaneous
- Male
- Random Allocation
- Rats
- Rats, Sprague-Dawley
|