Acute Electrophysiologic Elfects of Sodium Administration in Dogs Treated With O-Desmethyl Encainide

Conduction slowing is the major in vivo effect of sodium channel blocking drugs. Although this action may promote arrhythmia suppression, apparently paradoxical arrhythmia aggravation does occur. The latter outcome is most frequently seen during treatment with the class IC agents such as encainide or flecainide, which are potent depressors of conduction even at usual plasma concentrations and heart rates. Anecdotal reports in patients with such drug toxicity have suggested a beneficial effect of sodium lactate or NaHCO3 administration. The purpose of this study, therefore, was to examine the changes induced by sodium loading on the electrophysiologic properties of the canine ventricle pretreated with a class IC drug. Thirty dogs received loading and maintenance infusions of O-desmethyl encainide (ODE), an encainide metabolite that as a sodium channel blocker is approximately 10 times more potent than the parent drug. Interventions were administered during the maintenance phase when stable plasma ODE concentrations of 448±68 (SEM) ng/ml were present, and QRS was prolonged from 62±1 to 89+2 msec, and HV was prolonged from 28±1 to 50±1 msec. NaHCO3 (5 meq/kg during 1 minute) shortened QRS from 92±6 to 76±3 msec and shortened HV from 44±3 to 37±3 msec within 10 minutes (both p<0.01). NaHCO3 also significantly prolonged endocardial monophasic action potential duration from 231±22 to 272+33 msec and decreased serum [K+] from 3.8+0.2 to 3.0+±0.2 meq/l, but it did not alter plasma ODE concentration. Administration of a second sodium salt, NaCI (5 meq/kg during 1 minute), produced similar efects. Respiratory alkalosis did not alter QRS, HV, or monophasic action potential duration, whereas osmotic loading with mannitol increased QRS, HV, and monophasic action potential duration. Infusion of KCI to maintain serum [K'] constant during NaCI treatment blunted the changes in monophasic action potential duration but did not affect the QRS or HV shortening produced by NaCI alone. Short-term administration of NaHCO3 or NaCl can partially reverse ODE-induced conduction slowing, which may be an important factor in arrhythmia aggravation. This effect appears to be related to sodium loading itself rather than to concomitant changes in plasma drug concentration, pH, serum potassium concentration, or osmolality. (Circulation 1989;80:994-1002)