title: Flecainide augments muscle sympathetic nerve activity in humans.
abstract: The Cardiac Arrhythmia Suppression Trial has shown that treatment with flecainide is associated with an increased incidence of cardiac death in patients following myocardial infarction. It is believed that there is a complex mechanism involving an interaction between flecainide, sympathetic activation, and acute ischemia that is responsible for the increased risk of sudden death. The purpose of this study was to determine the effects of flecainide on muscle sympathetic nerve activity (MSNA) in humans. We measured MSNA using microneurography and cardiac output using the dye dilution method in 30 healthy individuals. Measurements were made at rest and after the oral administration of flecainide (200mg, n=12) or placebo (n=9), or intravenous administration of propranolol (0.2 mg/kg, n=9). Flecainide significantly increased heart rate and decreased the cardiac index (both p<0.01). Flecainide increased the burst rate from 16.7 +/- 3.5 to 23.3 +/- 4.1 bursts/min and the burst incidence from 26.6 +/- 5.1 to 34.7 +/ -5.6bursts/100 heartbeats (both p<0.01). For all of the hemodynamic parameters except heart rate, the effects of propranolol were similar to those of flecainide. Propranolol also increased the burst rate by 52 +/- 34% and the burst incidence by 106 +/- 39%. These results suggest that flecainide suppresses myocardial contractility and produces reflex-mediated increases in sympathetic nerve firing in humans.
authors.affiliation: Department of Cancer Gene Regulation, Gastroenterology and Nephrology, Graduate School of Medical Science, Kanazawa University, Japan. drnagata@nsknet.or.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nagata
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005424:Flecainide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013599:Systole / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D011433:Propranolol; D005424:Flecainide