The electrophysiological effects of hypoxia alone or combined with subtherapeutic concentrations of procainamide superfusion were investigated in guinea-pig ventricular muscle fibres in order to elucidate the procainamide activity on suffering myocardial cells. 2. A first 30 minute-long hypoxia depressed action potential characteristics but never induced cellular inexcitability. These alterations were entirely reversible. A second consecutive hypoxia period similarly affected cellular activity. 3. After a control hypoxia period, procainamide 0.15 microM and 1.5 microM further depressed or abolished the hypoxia-altered transmembrane potentials. 4. In procainamide 0.15 microM and 1.5 microM pretreated cells, hypoxia more extensively depressed or abolished the myocardial cell activity than in unpretreated cells. 5. It has been demonstrated that antiarrhythmic drugs only slowly and incompletely reached the ischaemic myocardium. The present results suggest that in clinical situations, such weak concentrations may be efficient for inducing pronounced modifications in ischaemic areas and rapid antiarrhythmic effects.
