title: Suppression of longitudinal versus transverse conduction by sodium channel block. Effects of sodium bolus.
abstract: BACKGROUND
  Arrhythmias resulting from treatment with sodium channel-blocking antiarrhythmic drugs have been successfully treated with sodium infusion, although the mechanism underlying this effect is uncertain.
  
  
  RESULTS
  In this study, we used a multielectrode array to examine the effects of O-desmethyl encainide (ODE), a potent sodium channel-blocking metabolite of encainide, on conduction in canine ventricle. ODE depressed both longitudinal and transverse conduction velocities in a plasma concentration-related fashion (r = -0.74, -0.60; p less than 0.001). At ODE concentrations less than or equal to 300 ng/ml (n = 34), conduction velocity was depressed to the same extent in the longitudinal (-21.9 +/- 8.4%, SD) and transverse orientations (-22.0 +/- 8.8%). However, at concentrations greater than 300 ng/ml (n = 17), conduction was significantly more impaired longitudinally than transversely (-44.5 +/- 11.7% versus -34.4 +/- 13.7%, p less than 0.02). In 12 animals with high concentrations (mean, 432 +/- 32 ng/ml), a 5-meq/kg bolus of sodium chloride over 1 minute immediately increased conduction velocity; this effect was significantly greater and longer lasting in the longitudinal orientation. In two animals, conduction block in the longitudinal orientation was documented at high plasma ODE and was immediately reversed by sodium bolus.
  
  
  CONCLUSIONS
  We conclude that the major effect of sodium in animals with excess sodium channel block is improvement of longitudinal propagation; this effect may underlie the antiarrhythmic action of sodium in the analogous clinical setting.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, Tenn. 37232-6602.
authors.forename: J
authors.initials: J
authors.lastname: Turgeon
authors.forename: T A
authors.initials: TA
authors.lastname: Wisialowski
authors.forename: W
authors.initials: W
authors.lastname: Wong
authors.forename: W A
authors.initials: WA
authors.lastname: Altemeier
authors.forename: J P
authors.initials: JP
authors.lastname: Wikswo
authors.forename: D M
authors.initials: DM
authors.lastname: Roden
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy; D004285:Dogs; D016700:Encainide / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; C033635:O-demethylencainide; D012965:Sodium Chloride; D016700:Encainide