title: L-carnitine treatment improves cardiac performance and restores high-energy phosphate pools in cardiomyopathic Syrian hamster.
abstract: Hamsters with either the dilated (BIO 53.58) or hypertrophic (BIO 14.6) form of cardiomyopathy and an inbred control strain of hamster (F1B) were treated for 6 months with high-dose L-carnitine (1 g/kg/day i.p.). After treatment, the animals were killed and their hearts perfused by the isolated working technique. Mechanical performance (as indicated by the double product of heart rate and left ventricular [LV] peak systolic pressure) of both carnitine-treated cardiomyopathic groups was increased significantly above their respective sham-treated groups. Associated with these increases in mechanical performance were significant increases in both peak-positive LV dP/dt (index of contractility) and peak negative dP/dt (index of relaxation) in both carnitine-treated myopathic groups. Serum carnitine levels were increased 10-15 times within 2 hours after injection of L-carnitine in all 3 groups. Myocardial free-carnitine levels were increased twofold in both control and dilated myopathic hearts above their respective sham-treated groups, restoring the level in the dilated hearts comparable to those of controls. Myocardial carnitine levels in the hypertrophic group were not significantly affected by treatment. Total high-energy phosphate stores, i.e., ATP plus creatine phosphate, were restored to control levels by L-carnitine treatment in both cardiomyopathic groups. Levels of the breakdown products of ATP were maintained primarily in the more readily convertible adenosine diphosphate and adenosine monophosphate forms in all three treated groups. These changes resulted in significantly higher ratios of (ATP)/(ADP + AMP + adenosine) and (creatine phosphate)/(creatine) in the treated hearts. This is the first study demonstrating that high-dose L-carnitine treatment results in improved cardiac performance and increased myocardial total high-energy phosphate stores in the Syrian hamster model with one of two distinct forms of cardiomyopathy, i.e., dilated or hypertrophic. The mechanisms for these effects of exogenous L-carnitine treatment cannot be totally explained by changes in oxidative energy metabolism.
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D009202:Cardiomyopathies / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D002331:Carnitine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D003065:Coenzyme A / Q000031:analogs & derivatives / Q000378:metabolism; D006224:Cricetinae; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000227:Adenine Nucleotides; D010710:Phosphates; D010725:Phosphocreatine; D002331:Carnitine; D003065:Coenzyme A