Lack of direct antiarrhythmic electrophysiological effects of salicylate on isolated guinea-pig myocardium

Conventional microelectrode techniques were used to study the influence of Na-salicylate, Na-benzoate, Na-2,6-dihydroxybenzoate and 2,4-dinitrophenol (2,4-DNP) on the action potential (AP) of guinea-pig papillary muscles and atria. In papillary muscles, Na-salicylate (0.19-1.87 mmol/l) concentration-dependently shortened the AP duration and the functional refractory period. The AP amplitude decreased slightly with the largest concentration, while the resting potential and the maximum depolarisation velocity (Vmax) were not affected. A concentration-dependent negative inotropic effect was also seen. All drug effects were reversible after washout. In atria, 6.24 mmol/l Na-salicylate induced a slight shortening of the AP duration, a decrease of the AP amplitude and Vmax, but no decrease of the contractile force. The effects of the uncoupling agent, 2,4-DNP (10 mumol/l), were similar to those of the largest concentration of Na-salicylate in papillary muscles and in atria. Na-benzoate and Na-2,6-dihydroxybenzoate had no significant influence on AP duration, AP amplitude, resting potential, Vmax, refractory period or force of contraction of either papillary muscles or atria. These results suggest that Na-salicylate exerts its effects on isolated guinea-pig myocardium by uncoupling the oxidative phosphorylation, whereas two other possible mechanisms of action, namely an increase of membrane surface charge and an inhibition of prostaglandin synthesis, seem to be of minor importance.