Ventricular electrophysiology of quinidine-propranolol combinations in the dog heart

The effects of quinidine and propranolol, singly and in combination, on certain electrophysiological responses were studied in open-chest dogs. Parameters measured were the diastolic threshold, conduction time, excitability and functional refractory period of canine right ventricular muscle. Potentiation was judged to have occurred if the combination of a half-dose of quinidine plus a half-dose of propranolol produced a significantly greater response than the full dose of either quinidine or propranolol. Two combinations were employed in this study: combination I contained 2.5 mg/kg of quinidine plus 0.1 mg/kg of propranolol while combination II contained 5.0 mg/kg of quinidine plus 0.2 mg/kg of propranolol. Results of the study indicated that combination II potentiated the activity of quinidine and propranolol to depress excitability, increase conduction time and prolong refractoriness. However, combination I only potentiated the change in refractory state. Neither combination potentiated the individual drug action to increase the diastolic threshold. From the results of this study, it may be concluded that the combination was especially effective in prolonging ventricular refractoriness which may account to a significant degree for the enhanced therapeutic effectiveness of the combination in resistant ventricular arrhythmias.