Energy metabolism of the hypertrophied heart studied by 31P nuclear magnetic resonance.

Abstract

We report studies on the isolated hearts of rats treated with triiodothyronine (0.2 mg/kg daily) for 14 days, on spontaneously hypertensive rats (12 and 21 weeks old, Lyon strain) and on their respective controls. A 30% increase in cardiac weight was developed with triiodothyronine and a 40% increase in heart weight in the presence of spontaneous hypertension. The hearts were perfused in the presence of 2 mM pyruvate and the intracellular content of phosphocreatine, inorganic phosphate and ATP measured by nuclear magnetic resonance spectroscopy with 31P. The left ventricular developed pressure was measured with an intraventricular balloon. Changes in contractile strength were induced by stepwise modifications of the extracellular concentration of calcium from 0.5 mM to 1.0, 1.5 and 2.0 mM. In all experimental groups, each increase in the extracellular calcium induced an increase in the developed pressure, together with a decrease in phosphocreatine and an increase in inorganic phosphate; the ATP level remained unchanged. These metabolic changes increased progressively with the increase in developed pressure. In the hearts of animals treated with triiodothyronine and of the 21 weeks old hypertensive rats, the extent of changes in phosphocreatine and inorganic phosphate was the same as in the controls; but, in the hearts of 12 weeks old hypertensive rats, the changes were significantly greater than in their controls. These observations suggest that, during the development of cardiac hypertrophy from spontaneous hypertension, there is a transitory deficiency in the capacity for aerobic ATP production relative to the rate of hydrolysis of ATP induced by an inotropic effect.