Effect of L-carnitine on mitochondrial acyl CoA esters in the ischemic dog heart.
Many studies have shown that L-carnitine has a positive effect on ischemic myocardium, probably by reducing accumulation of long-chain acyl coenzyme A (CoA) esters. Previous studies have involved whole-heart extracts and have not assessed changes of CoA ester levels in mitochondria, the site of translocase inhibition. To more precisely assess L-carnitine effects, we measured long-chain acyl CoA ester levels in cytosol and in mitochondria in the ischemic canine heart. Dogs were divided into four groups: a sham-operated control group; an untreated group; and high- and low-dose L-carnitine-treated groups (30 mg/kg and 100 mg/kg). After 60 min of ischemia, the heart was excised, and the cytosolic and mitochondrial fractions were isolated. CoA esters and the activity of carnitine palmitoylcarnitine transferase (CPT) I and II were measured in both compartments. Approximately 89% of cellular free CoA. 90% of cellular acetyl CoA, 97% of cellular shot-chain acyl CoA, and 92% of cellular long-chain acyl CoA were located in the mitochondrial space under the normal condition. Under the ischemic condition, mitochondrial free CoA was significantly decreased. Conversely, mitochondrial acetyl CoA and long-chain acyl CoA were significantly increased. Treatment with L-carnitine significantly decreased acetyl CoA and long-chain acyl CoA in the ischemic mitochondrial space in a dose-dependent manner. These results support the hypothesis that L-carnitine reduces accumulation of long-chain acyl CoA within the ischemic mitochondrial space and thereby improves mitochondrial function and adenine nucleotide translocation.
Kobayashi
A
A
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Fujisawa
S
S
D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D003065:Coenzyme A / Q000032:analysis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions
D004952:Esters; D002331:Carnitine; D003065:Coenzyme A