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

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.

Systolic aortic pressure-time area is a useful index describing arterial wave properties in rats with diabetes

“…Two-month-old male Wistar rats were randomly divided into 3 groups, as follows: (1) NC ( n = 27), (2) type 1 DM ( n = 25), and (3) type 2 DM ( n = 12). Type 1 DM was induced by using a single tail-vein injection with 55 mg kg −1 of STZ (Sigma, St. Louis, MO, USA) in a 0.1 M citrate buffer (pH 4.5) (Sigma, St. Louis, MO, USA) 13 . Type 2 DM was induced by administering intraperitoneally 180 mg kg −1 of NA (Sigma, St. Louis, MO, USA) 30 min before an intravenous injection of 50 mg kg −1 of STZ dissolved in 0.1 M citrate buffer (pH 4.5) 34 35 .…”

“…Diabetes mellitus (DM) is a complex metabolic disorder 8 9 , which is thought to be responsible for impaired hemodynamic load 10 11 and manifests the diabetic cardiomyopathy 12 13 . In this study, we investigated the possibility of systolic aortic pressure-time area ( PTAs ) acting as systolic LV workload in rats with diabetes.…”

Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats

“…We have previously described procedures for measuring MDA/TBARS (Wang et al, 2013 ). In brief, rat cardiac tissues were stored at −80°C until further analysis.…”

“…We have previously described procedures for characterizing the cardiac pumping mechanics from the elastance-resistance model (Wu et al, 2008 ; Wang et al, 2013 ). In brief, one can predicted the model-derived pressure of the left ventricle if the model parameters could be previously identified (Campbell et al, 1986 ; Shroff et al, 1992 ).…”

“…We have previously described procedures for defining the LV end-systolic equilibrium point (Wang et al, 2013 ). In brief, the time integration of aortic flow (red curve in Figure 2A ) and the measured LV pressure (red curve in Figure 2B ) were used to construct the pressure-ejected volume loop.…”