Control of energy production in cardiac muscle: effects of ischemia in acidosis

Abstract

Evidence is summarized indicating that mitochondrial respiration and citric acid cycle activity in the intact heart are controlled by the cytosolic phosphate potential and mitochondrial NAD oxidation-reduction state. Data are presented showing that the effect of respiratory acidosis is greater than that of metabolic acidosis in inhibiting left ventricular pressure development in the perfused rat heart, because of a greater fall of intracellular pH under the former conditions. Respiratory acidosis is shown to be readily associated with tissue hypoxia as a result of an increased vascular resistance and diminished flow rate through the coronary circulation. In nonischemic respiratory acidosis, the rate of ATP production is well balanced by the rate of ATP utilization, and tissue ATP and creatine-P levels remain approximately normal. Partially ischemic respiratory acidosis was associated with low tissue levels of ATP and creatine-P and high tissue levels of lactate and NADH. Ischemic areas with sharp border zones were visualized during and after an abrupt decrease of perfusion fluid pH by directly photographing NADH fluorescence from the surface of perfused hearts. Reversal of the hypodynamic state with partially ischemic respiratory acidosis could not be achieved by augmenting the coronary flow by means of an external pump. The demonstration of the existence of sharp zones of high pyridine nucleotide fluorescence adjacent to normal zones indicates a great heterogeneity of coronary perfusion and the existence of steep oxygen gradients in the intact heart.