Reversal of strophanthidin negative inotropy by metabolic substrates in cardiac Purkinje fibres

The action of substrates and metabolic inhibitors on strophanthidin inotropy was studied in canine cardiac Purkinje fibres perfused in vitro. Both membrane potentials and contractile force were recorded. The results show that: 1) pyruvate (1 to 10 mmol X litre-1) decreases and then increases contractile force in Tyrode solution or in the presence of a low concentration of strophanthidin without modifying the action potential magnitude or configuration; 2) during the decreasing (but not the increasing) phase of strophanthidin (2 to 5 X 10(-7) mol X litre-1) inotropy, pyruvate increases contractile force; 3) beta-hydroxybutyrate has effects similar to those of pyruvate; 4) glucose increases contractile force and more so during the descending phase of strophanthidin inotropy; 5) the positive inotropic effect of pyruvate during declining strophanthidin inotropy is not prevented by glucose-lack and/or by iodoacetate but is markedly reduced in a hypoxic solution; 6) in contrast, glucose under similar conditions has the usual effects in hypoxia but not in the presence of iodoacetate; 7) the combination of hypoxia and glucose-lack leads to a decline in contractile force and to contracture: strophanthidin increases both contractile and resting force whereas O2 and/or glucose relax the contracture; 8) pyruvate has a positive inotropic effect also in the presence of high (greater than 10 mmol X litre-1) calcium. It is concluded that the decline in contractile force during exposure to strophanthidin or high calcium can be reversed by providing suitable substrates and therefore may involve a deficit in the production of high energy phosphates.