Dependence of myocardial redox systems on the concentration of exogenous substrate

Isolated rat hearts were perfused according to Langendorff at a range of perfusion pressures and the variations of intracellular oxygenation were studied under these conditions by optical methods. The oxygen consumption was directly related to left ventricular performance in all cases examined, the relationship being independent of both the substrate used (glucose, beta-OH-butyrate) and its concentration (2.5, 5.0, 10.0 mM). The changes in the respiratory rate were accompanied by modifications of the redox state of mitochondrial enzyme systems (reduced nicotinamide adenine dinucleotide (NADH), cytochromes) in presence of low concentration (2.5 mM) of substrate. At higher substrate concentrations (5.0, 10.0 mM), however, no change in the redox state of cytochromes and only inconsistent fluctuations of that of NADH were observed. These results suggest that the generally accepted relationship between the rate of electron transport and the degree of reduction of respiratory coenzymes exists only under special conditions (low substrate concentration). Other factors, such as the size of the pool of hydrogen available, should be considered. Furthermore, this work specifies the optimal experimental conditions for the study of mitochondrial respiratory transitions (low substrate) in the intact myocardium by means of direct optical techniques.