Acetyl-l-carnitine and oxfenicine on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats.
BACKGROUND
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.
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Chih-Hsien
CH
Wang
Shoei-Shen
SS
Wang
Wen-Je
WJ
Ko
Yih-Sharng
YS
Chen
Chun-Yi
CY
Chang
Ru-Wen
RW
Chang
Kuo-Chu
KC
Chang
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D004791:Enzyme Inhibitors; D000108:Acetylcarnitine; C023010:4-hydroxyphenylglycine; D005998:Glycine