title: Hypertonic sodium bicarbonate partially reverses QRS prolongation due to flecainide in rats.
abstract: Hypertonic (1M) sodium bicarbonate can partially reverse the cardiac toxicity of some Class IA antiarrhythmic agents, presumably by antagonizing sodium channel inhibition. We studied the effects of 1M sodium bicarbonate on toxicity due to the Class IC drug flecainide. Anesthetized rats received i.v. loading and maintenance doses of flecainide to produce QRS prolongation of 76% that was stable over the 60 min study period. 20 min after the start of the maintenance infusion, groups of 8 rats received an i.v. infusion of 1M sodium bicarbonate (6 meq/kg) or an equal volume of 0.9% saline. QRS prolongation was reduced by 1M sodium bicarbonate but not only 0.9% saline (% change -12.2 +/- 10.0 v. +3.0 +/- 2.7, p = 0.001). Expressed as a percent of the flecainide-induced QRS prolongation, bicarbonate reduced this prolongation by 26.5%. The improvement in QRS duration persisted until sacrifice 30 min later. Compared to controls, the bicarbonate group had a significantly higher blood pH (7.55 +/- 0.06 v. 7.44 +/- 0.05) and serum sodium concentration (149 +/- 5 v. 137 +/- 2 meq/l). Serum flecainide concentrations were similar. These data suggest that 1M sodium bicarbonate can partially reverse flecainide-induced conduction delay in rats. This effect may be due to changes in the extracellular pH and sodium concentration. 1M sodium bicarbonate may be useful in assessing the role of sodium channel inhibition in mediating the toxicity of flecainide or other Class IC drugs.
authors.affiliation: Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota 55415.
authors.forename: D E
authors.initials: DE
authors.lastname: Keyler
authors.forename: P R
authors.initials: PR
authors.lastname: Pentel
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000517:prevention & control; D001639:Bicarbonates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography; D005424:Flecainide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006982:Hypertonic Solutions; D008297:Male; D051381:Rats; D012964:Sodium / Q000494:pharmacology*; D017693:Sodium Bicarbonate
chemical_list: D001639:Bicarbonates; D006982:Hypertonic Solutions; D017693:Sodium Bicarbonate; D012964:Sodium; D005424:Flecainide