We continue to apply 13C NMR methods for analysis of metabolism in the isolated rat heart. Over the last year one target has been analysis of metabolism in hypertrophied heart tissue. Earlier studies indicated that energy production from exogenous fatty acids or carbohydrates and from endogenous energy stores may be substantially disrupted in left ventricular hypertrophy. The contribution of long chain fatty acids (0.35 mM), lactate (1.2 mM), pyruvate (0.09 mM), glucose (5.5 mM), acetoacetate (0.12 mM), a-hydroxybutyrate (0.05 mM), and endogenous sources to energy production was determined by 13C NMR isotopomer analysis in two standard models of left ventricular hypertrophy, the spontaneously hypertensive rat and the aortic banded Sprague-Dawley rat. The fraction of acetyl-CoA derived from various sources was not different between the two control groups: fatty acids, 0.46-0.56; lactate plus pyruvate, 0.25-0.32; ketones, 0.11-0.12; glucose, 0.03-0.05; and endogenous sources, 0.03-0.06. However, oxidation of fatty acids was significantly decreased in spontaneously hypertensive rats (0.20 q 0.02 of acetyl-CoA production, mean q s.d.) or in banded Sprague-Dawley rats (0.24 q 0.04 of acetyl-CoA production). Ketone and octanoate oxidation was unaffected by hypertrophy. Oxidation of glucose and glycolysis was increased in both models of pressure overload, but the overall contribution of glucose to oxidative energy production remained modest. In contrast, oxidation of lactate and pyruvate was stimulated by hypertrophy to the extent that their metabolism provided most of the energy production even at physiological concentrations. (Service 9) REPORT PERIOD: (09/01/97-08/31/98)
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