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. Conclusion: Ghrelin treatment results in dose-dependent beneficial effects on body weight and body composition, but does not improve cardiac function. (C) 2008 Elsevier Ireland Ltd. All rights reserved.