title: Acute electrophysiologic effects of sodium administration in dogs treated with O-desmethyl encainide.
abstract: 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors.forename: A K
authors.initials: AK
authors.lastname: Bajaj
authors.forename: R L
authors.initials: RL
authors.lastname: Woosley
authors.forename: D M
authors.initials: DM
authors.lastname: Roden
mesh_terms: D000472:Alkalosis, Respiratory / Q000503:physiopathology; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D004285:Dogs; D004569:Electroencephalography; D004594:Electrophysiology; D016700:Encainide / Q000031:analogs & derivatives*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate; D006985:Hyperventilation / Q000503:physiopathology; D008297:Male; D012964:Sodium / Q000494:pharmacology*; D017693:Sodium Bicarbonate; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000813:Anilides; D001639:Bicarbonates; C033635:O-demethylencainide; D012965:Sodium Chloride; D017693:Sodium Bicarbonate; D012964:Sodium; D016700:Encainide