965-53 Myocardial Glycolytic and Fatty Acid Metabolism During Progression of Adriamycin (ADR)-Induced Heart Failure in Rats

To investigate the changes in myocardial glycolytic and fatty acid metabolism during progression of ADR-induced heart failure, sixty five 8-weeks male S-D rats were injected intraperitoneally with ADR (15 mg/kg) or equivalent volume of saline, divided into 6 times for 2-weeks. Rats were sacrificed and the left ventricles were removed, at 1 day (ADR 10 group, Control 10 group), at 3 weeks (ADR 3W group, Control 3W group) and at 6 weeks (ADR 6W group, Control 6W group) after the last ADR or saline injection. By using proton-MRS, we measured myocardial metabolites (lactate and alanine as indices of glycolytic metabolism, and free carnitine as an index of fatty acid metabolism). As an index of energy production, high energy phosphate (ATP) in the myocardium was also measured by HPLC. Results The cumulative mortality rate was 0% in control groups and 48% in ADR-treated groups during observed period. The mortality rate was abruptly increased 3 weeks after the last injection. lactate alanine free carnitine ATP Control 1D (n = 6) 11.85 ± 0.98 1.12 ± 0.0 1.07 ± 0.08 8.52 ± 0.32 Control 3W In = 6) 11.22 ± 0.91 1.14 ± 0.09 1.12 ± 0.09 8.60 ± 0.38 Control 6W (n = 4) 13.10 ± 1.68 1.58 ± 0.23 1.05 ± 0.12 8.90 ± 0.19 lactate, alanine, free carnitine, μ mol/wet g, ATP, nmol/mg protein No significant changes in tissue levels of lactate, alanine, free carnitine and ATP were observed among Control groups lactate alanine free carnitine ATP ADR 10 (n = 6) 15.72 ± 1.38 2.10 ± 0.23 1.05 ± 0.07 7.23 ± 0.51 ADR 3W(n = 6) 3.47 ± 0.41 1.02 ± 0.24 0.83 ± 005 598 ± 0.16 ADR 6W(n = 6) 9.10 ± 0.76 1.28 ± 0.17 0.60 ± 007 4.70 ± 038 In ADR 1D, the tissue levels of lactate and alanine were significantly higher than those of Control 1D (p l 0.05), although the tissue levels of free carnitine and ATP were preserved. However, in ADR 3W, the tissue levels of free carnitine and ATP were significantly lower than those of Control 3W (p l 0.05). The tissue levels of free carnitine and ATP appeared to be further reduced in ADR 6W. Conclusion This study demonstrated that the impaired energy production had already occurred even at early stage of ADR-induced heart failure.