Functional and biochemical effects of a K(+)-ionophore on the isolated perfused rat heart

Valinomycin, a K(+)-specific ionophore, influenced function and metabolism of isolated perfused rat hearts in a dose-dependent fashion. At a concentration of 0.05 micrograms ml-1 in perfusion fluid a 50% reduction of heart rate (HR) and a 90% reduction in max dP/dt were observed. These effects were paralleled by a substantial decrease of myocardial energy charge from about 0.80 to 0.20. A 2.5 fold increase in tissue lactate concentration indicated an increased rate of glycolytic activity. Low ATP combined with high ADP and AMP levels as found in these valinomycin-treated hearts is known to promote phosphofructokinase activity and may explain the elevated lactate levels. A significant increase in the concentrations of adenosine, IMP and inosine was observed as well.