Effects of changes in the concentrations of substrate and oxygen on the perfused rabbit heart

Rabbit hearts were perfused with bicarbonate-buffered fluid containing 1.0 mM glucose and 1.5 mM lactate. Pairs of redox substrates were measured in the perfusion fluid and the heart after perfusate concentrations of beta-hydroxybutyrate (beta-HB) and oxygen were varied. The perfusate lactate to pyruvate ratio was shown to accurately represent the tissue ratio. The intracellular redox state varied independently of changes in substrate uptake. Increasing perfusate beta-HB concentration caused increased beta-HB uptake, decreased lactate uptake, and unchanged glucose uptake. Decreased perfusate oxygen tension caused inhibition of lactate and beta-HB uptakes and, when exteme, caused increased glucose uptake. The combination of a modest reduction in oxygen tension and increased perfusate beta-HB concentration caused a more reduced environment in the tissue than either change by itself. This combination of changes may have additive deleterious effects as suggested by clinical observations.