Abstract 777: Increased Carbohydrate Metabolism in Early Stage Heart Failure Compensates for a Near Complete Loss in Endogenous Fatty Acid Oxidation
Left ventricular hypertrophy (LVH) is associated with a greater reliance on glucose. Recent studies show this increase is not necessarily balanced to changes in exogenous fatty acid oxidation. Whether altered carbohydrate use compensates for a change in oxidation of endogenous fatty acids (Endo FA) in LVH is unknown. This study employed kinetic 13C NMR analysis of the oxidation of exogenous palmitate (PALM), endogenous fatty acids (Endo FA), exogenous glucose (GLUC), and endogenous glucose from glycogen (GLY). Isolated hearts from 12 week aortic-banded (LVH, n=7) and sham (S, n=7) operated rats were perfused with buffer containing either 5 mM glucose + 0.4 mM 13C palmitate, or 13C glucose + unlabeled palmitate for 30 min in a 14 T NMR magnet. Studies were repeated during inotropic challenge (0.01 microM isoproterenol, n=14). At baseline workload, PALM oxidation rate (LVH= 1.0 ± 0.1 micromol/min/g dw, S= 1.7 ± 0.2; p<0.01) remained similarly coupled to workload in S and LVH (rate pressure product: LVH= 22 ± 6 K mmHg*bpm, S= 35 ± 12 K; p<0.05), as both PALM oxidation and RPP were 37% lower in LVH. Carbohydrate oxidation was 33% greater in LVH compared to S at baseline (contribution to MITO ATP production; LVH: GLUC 14%, GLY 13%, versus S: GLUC 10%, GLY 8%). Surprisingly, there was no evidence of endogenous fat oxidation in LVH (LVH: Endo FA 0%, PALM 72%; vs Sham: Endo FA 8%, PALM 74%). With inotropic challenge, RPP doubled in both groups, and PALM oxidation rate increased (LVH ISO= 1.5 ± 0.8 micromol/min/g vs. S ISO= 3.0 ± 0.5, p<0.05). MITO ATP production from Endo FA remained negligible in LVH (LVH ISO = 0%, S ISO = 8%), and the contribution from PALM dropped 18% from baseline (LVH ISO= 59%, S ISO = 70%). Reduced PALM oxidation was balanced by GLUC and GLY oxidation (LVH ISO: GLUC 20%, GLY 22%; S ISO: GLUC 11%, GLY 11%). These findings indicate that glucose use compensated for the lack of Endo FA oxidation in LVH. Low Endo FA oxidation cannot be attributed to workload differences between LVH and shams, because Endo FA was not recruited by inotropic challenge. These findings have implications on the progression of LVH, particularly lipotoxic effects, given emerging evidence to link disruption of myocardial substrate use to cardiomyopathy.