Effects of Acetyl-L-Carnitine and Oxfenicine on the Cardiac Pumping Mechanics in Streptozotocin-Induced Diabetic Rats

• Main Authors: Chih-Hsien Wang, 王植賢
• Other Authors: 張國柱
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/79971152709057721800

博士 === 國立臺灣大學 === 生理學研究所 === 102 === 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 (Emax) and the theoretical maximum flow (Qmax). Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax 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 Emax associated with the unaltered Qmax. 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 Emax, which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Qmax showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Qmax 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.