Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats.
BACKGROUND
Streptozotocin-induced diabetes (STZ-D) in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement.


OBJECTIVE
The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats.


METHODS
Wistar rats (48) were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24) were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA) were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks.


RESULTS
The heart rates for the STZ-D rats (290 +/- 19 bpm) were less than control rats (324 +/- 20 bpm) (p < 0.05). After 4 weeks of oral carnitine supplementation, the serum carnitine and heart rates of the STZ-D rats returned to normal. Dobutamine stress increased the heart rates of all study animals, but the increase in STZ-D rats (141 +/- 8 bpm) was greater than controls (79 +/- 8 bpm) (p < 0.05). The heart rates of STZ-D rats given oral carnitine, however, were no different than controls (94 +/- 9 bpm). The left ventricular mass/body weight ratio (LVM/BW) in the diabetic animals (2.7 +/- 0.5) was greater than control animals (2.2 +/- 0.3) (p < 0.05) after 18 weeks of diabetes. In contrast, the LVM/BW (2.3 +/- .2) of the STZ-D animals receiving supplemental carnitine was the same as the control animals at 18 weeks.


CONCLUSIONS
Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.
Malone
John I
JI
The Department of Pediatrics, University of South Florida, College of Medicine, Tampa, FL 33612, USA. jmalone@hsc.usf.edu
Cuthbertson
David D
DD
Malone
Michael A
MA
Schocken
Douglas D
DD
D000284:Administration, Oral; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002331:Carnitine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology; D004452:Echocardiography; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D002331:Carnitine; D004280:Dobutamine; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin