Acetyl-l-Carnitine and Oxfenicine on Cardiac Pumping Mechanics in Streptozotocin-Induced Diabetes in Male Wistar Rats

INTRODUCTION: In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function. For this study, we compared the effects of acetyl-l-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship. METHODS: Diabetes was induced by a single tail vein injection of 55 mg kg(−1) streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L(−1) in drinking water) or oxfenicine (150 mg kg(−1) by oral gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (E (max)) and the theoretical maximum flow (Q (max)). Physically, E (max) reflects the contractility of the myocardium as an intact heart, whereas Q (max) has an inverse relationship with the LV internal resistance. RESULTS: When comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in E (max) associated with the unaltered Q (max). Acetyl-l-carnitine (but not oxfenicine) had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However, treating with acetyl-l-carnitine or oxfenicine resulted in an increase in E (max), which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Q (max) showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Q (max) corresponded to an increase in total vascular resistance when treated with oxfenicine. CONCLUSIONS: Acetyl-l-carnitine, but not oxfencine, optimizes the integrative nature of cardiac pumping mechanics by preventing the diabetes-induced deterioration in myocardial intrinsic contractility associated with unaltered LV internal resistance.