The influence of age and sex on disease development in a novel animal model of cardiac cachexia

Pre-clinical studies in cardiac cachexia have mostly been performed in young male rats. These models define cachexia only as a reduction in weight gain rather than weight loss. In this pilot study, we aimed to establish a model of genuine weight loss following chronic heart failure. Methods: Nine months old Sprague Dawley rats (10 male and 11 female) were kept under standard conditions. Weight was monitored weekly and body composition was assessed every 4 weeks over a period of 13 weeks prior to myocardial infarction (MI) surgery. After surgery, body weight was assessed twice weekly and body composition was analysed once weekly. Cardiac function was monitored before and after MI surgery. Results: Prior to MI surgery, all rats displayed stable body weight (male: 574 +/- 7 g, female: 294 +/- 6 g). Within the first week after surgery, male animals lost 43 +/- 9 g (p=0.001), but female rats remained weight stable (p > 0.5). Lean mass (male: 399 +/- 2 g; female: 222 +/- 3 g) and fat mass (male: 99 +/- 1 g; female: 46 +/- 2 g) were stable before surgery. MI induction led to a loss of -22.5 +/- 5.6 g lean mass (p=0.028) and 14.7 +/- 3.7 g fat mass (p=0.02) in males, while females showed no significant changes (both p > 0.5). Two weeks after surgery, male rats began to regain lean mass, but no change was observed for fat mass. Conclusion: Adult rats display a decline in body weight after MI and are therefore a better model for studies of cardiac cachexia. This effect is only seen in male rats, while females remain weight stable. The cause of this gender effect needs further investigation. (c) 2009 Published by Elsevier Ireland Ltd.