Abstract
IntroductionIn 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.MethodsDiabetes 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.ResultsWhen 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.ConclusionsAcetyl-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.
Highlights
In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function
It has been established that diabetes results in a cardiomyopathy, and increasing evidence suggests that an altered substrate supply and utilization by cardiac myocytes could be the primary injury in the pathogenesis of this specific heart muscle disease [1,2]
All values are expressed as means 6 SE
Summary
In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function. Patients with diabetes have an impaired cardiac glucose oxidation shifted toward a greater uptake and usage of free fatty acids (FFA) with reduced metabolic efficiency [3]. These alterations in cardiac metabolism may be responsible for both the increased susceptibility of the diabetic heart to myocardial ischemia and a proportionally greater decrease of myocardial performance [4,5]. In the treatment of patients with diabetes, one objective is an improvement of cardiac carbohydrate metabolism to alleviate myocardial ischemia and left ventricular (LV) dysfunction [6]. An alternative approach to achieve a switch in energy substrate preference, away from FFA metabolism and toward glucose metabolism, is to inhibit FFA uptake by the mitochondria using CPT-1 inhibitors
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