[Influence of heart work and substrate uptake on the regulation of pyruvate dehydrogenase activity in isolated guinea pig hearts (author's transl)].

In isolated guinea pig hearts performing a defined stroke work, the influence of heart work and substrate uptake on the interconversion of pyruvate dehydrogenase (PDH) was studied. When hearts from fasted animals are perfused with a salt solution containing 10mM glucose, an increase in cardiac output and aortic pressure effects an increase in active PDH from 50 to 74% of total PDH activity and a decrease in tissue content of energy-rich phosphates. Pyruvate turnover calculated from oxygen consumption corresponds with PDH activity. Under these experimental conditions, PDH activity might either represent the rate limiting step of oxidative glucose breakdown, or it might be adjusted to a flux rate controlled by other factors. In fed animals, PDH activity exceeds the pyruvate turnover. However, an increase of heart work raises the active PDH from 76 to 95%. Addition of 10 mM acetate to the perfusion medium decreases PDH activity and glucose uptake. In fed animals, an increase of heart work raises the active PDH from 43 to 59% only, whereas in fasted animals this effect is abolished. The effect of changes in heart work on PDH interconversion might be explained by changes in energy-rich phosphate concentrations. However, substrate uptake and nutritional state may interfere or even abolish this effect.