Abstract 514: Metabolomic Analysis of the Transition from Cardiac Hypertrophy to Failure
Metabolomic analysis is an emerging tool for simultaneously measuring the amounts of metabolites of multiple metabolic pathways. Using capillary electrophoresis time-of-flight mass spectrometry, we profiled heart metabolites of rats that showed a distinct transition from compensated hypertrophy to heart failure. Dahl salt-sensitive rats fed a high-salt diet developed hypertension and left ventricular hypertrophy (LVH) at 11 weeks of age and congestive heart failure (CHF) at 17–19 weeks. We administered dichloroacetate (DCA, 80mg/kg/day) or vehicle beginning at 11 weeks. DCA is an activator of pyruvate dehydrogenase and increases glycolysis and glucose oxidation. DCA did not change the blood pressure or left ventricular weight in CHF rats. DCA preserved cardiac function (fractional shortening on echocardiography, CHF 29± 2.2% and DCA 42± 2.1%, p<0.05) and improved the survival of CHF rats (CHF 37% and DCA 65%, p<0.05). With metabolomic analyses of the hearts, 114 metabolites of multiple metabolic pathways were quantified. The amounts of 14 metabolites were different between a low-salt group (11 weeks of age fed a low-salt diet) and LVH, and the amounts of 19 metabolites were different between LVH and CHF. DCA treatment increased the reduced-form of glutathione and the NADPH/NADP+ ratio compared to CHF by 66% and 25%, which suggests that the pentose phosphate pathway is an effector of DCA since NADPH and glutathione reduce oxidative stress. In conclusion, the development of LVH and CHF was associated with distinct changes in the metabolomic profile. Metabolomics appears to be a useful tool for identifying biomarkers and future therapeutic targets in heart failure.