Protection of the ischemic dog myocardium with carnitine

In 25 open chest anestheslzed dogs, left anterior descending coronary arterial blood flow was measured with an electromagnetic flowmeter while aortic blood pressure and epicardlal electrocardiograms were recorded. Ischemia was produced in the left anterior descending arterial bed by decreasing mean flow to one third of control levels for a 5 minute period with a micrometer snare device. This produced an increase in S-T segment deviation greater than 4 mv in the ischemic bed. Control and ischemic left anterior descending arterial bed tissue samples were obtained by drill biopsy and were analyzed for adenosine triphosphate (ATP) and creatine phosphate levels and adenlne nucleotide translocase activity. The ATP levels decreased from 5.6 ± 1.2 to 3.6 ± 1.4 μmoles/g, and creatine phosphate decreased from 15.3 ± 4.6 to 5.8 ± 3.8 μmoles/liter. The adenine nucleotide translocase activity decreased from an average control value of 42,957 ± 9,480 to 29,100 ± 6,609 disintegrations per minute (dpm)/mg during the 5 minute period of ischemia. With the ischemia maintained, 100 mg/cc of L-carnitine was infused into the ischemic left anterior descending arterial bed at a rate of 1 cc/min for 5 minutes (17 dogs), and 80 mg/kg of D-L carnltine was given intravenously in 8 dogs. The epicardial S-T segment deviation decreased to approximately 2 mv after the carnltine infusion, with ischemia maintained. A third biopsy sample of the ischemic bed showed that the ATP level had increased to 5.2 ± 1.1 and the creatine phosphate to 10.8 ± 4.8 moles/g; the adenine nucleotide translocase activity had increased to 37,800 ± 7,210 dpm/mg. In 9 dogs ventricular fibrillation developed at this level of ischemia before infusion of carnitine, whereas only one dog had fibrillation at comparable levels of ischemia after infusion.

These results support the hypothesis that infusion of carnitine may benefit the ischemic myocardium by maintaining tissue levels of free carnitine, reversing inhibition of adenine nucleotide translocase by long chain acyl coenzyme A esters and in this manner restoring mitochondrial function.