Effect of application route of the ghrelin analog BIM-28131 (RM-131) on body weight and body composition in a rat heart failure model.

ABSTRACT

Chronic heart failure (CHF) remains one of the most challenging diseases in terms of numbers and disease management, particularly so, if the CHF patient develops cardiac cachexia. Ghrelin and its analogs have been suggested to improve body weight and cardiac function in heart failure models and exploratory human clinical studies. However, most ghrelin compounds are peptides and need to be injected several times per day, which affects the quality of life of patients. Here, we compared two application routes, three times daily subcutaneous (sc) injections to continuous infusion using osmotic mini-pumps in a rat model of CHF. Moreover, the effects were also compared to three times daily sc injections of growth hormone (GH). Rats were treated for 28 d. The results show that treatment with 50 or 100 nmol/kg/d BIM-28131 (RM-131) potently induces body weight gain, fat and lean mass compared to placebo. The gain of lean mass was equal to the gain of lean mass in the 2mg/kg/d GH group and superior to 250 µg/kg/d GH. Both GH and BIM-28131 increased levels of insulin-like growth factor-1 to a similar extent. Little effect was seen on cardiac function; only cardiac output was improved by either high dose BIM-28131 or GH. Overall the effects of BIM-28131 were similar in both application routes.