The time courses of the changes in contractile force and in transmembfane potentials induced by cardiac glycosides in guinea-pig papillary muscle.

1. The effects of ouabain, digoxin, digoxigenin monodigitoxoside, digoxigenin bisdigitoxoside and digitoxigenin bisdigitoxoside on the force of contraction and on the transmembrane action potential were compared in isolated papillary muscles of guinea-pigs.2. All cardiac glycosides studied had a dose-dependent positive inotropic effect and simultaneously shortened the duration of the action potential at all levels of repolarization from the start of drug action.3. In every instance, the reduction of the action potential duration developed more slowly than the increment in contractile force. However, the ratios between the two rates were independent of the concentrations used and seemed to be characteristic for the individual cardiac glycosides.4. All cardiac glycosides had a biphasic effect on the time-to-peak tension. An initial increase was followed by a dose-dependent decrease.5. The results are discussed with respect to the possible sites of action. Taking into account the different rates as well as the different ratios, it is proposed that more than one site of action is involved in producing the different effects of cardiac glycosides on heart muscle.