title: Acute electrophysiologic effects of intravenous amiodarone are independent of a sympatholytic action in humans.
abstract: Previous experiments in animals demonstrated a novel sympatholytic action of acute intravascular amiodarone (AM). It is not known if this action also occurs in humans. Twelve male volunteers performed handgrip for 10 min before and after 300 mg intravenous (IV) AM over 60 min. The effect of handgrip was determined from changes in blood pressure (BP), heart rate (HR), and cardiac noradrenaline (NA) spillover. Changes in cardiac spillover of dihydroxyphenylglycol (DHPG), the metabolite of NA, were measured during AM infusion. The electrophysiological effects of AM were determined from changes to the A-H intervals during right atrial stimulation (100 beats/min). Handgrip increased HR (63 +/- 2 to 84 +/- 5 beats/min and 65 +/- 3 to 84 +/- 4 beats/min), systolic BP (141 +/- 4 to 179 +/- 6 mm Hg and 140 +/- 4 to 179 +/- 7 mm Hg), and cardiac NA spillover (11.9 +/- 4 to 44.3 +/- 13 ng/min and 17.3 +/- 4 to 55.5 +/- 11 ng/min) before and after AM, respectively (P < 0.02 in all groups). There was good correlation between increases in cardiac NA spillover and HR (r2 = 0.86) and systolic BP (r2 = 0.87). AM increased the A-H interval (95.5 +/- 18 to 107.8 +/- 20 ms, P < 0.02). There was no difference in hemodynamic or NA response to handgrip before or after the AM infusion. There was also no change in DHPG cardiac spillover during AM infusion. Acute IV AM did not exert a sympatholytic action in humans, with no attenuation in hemodynamic or NA response to handgrip or increase in DHPG production, despite producing an electrophysiologic response.
authors.affiliation: Baker Heart Research Institute, Melbourne, Australia.
authors.forename: Deepak
authors.initials: D
authors.lastname: Haikerwal
authors.forename: Murray D
authors.initials: MD
authors.lastname: Esler
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dart
mesh_terms: D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000494:pharmacology*; D016275:Atrial Function / Q000502:physiology*; D002036:Bundle of His / Q000502:physiology; D004562:Electrocardiography; D004594:Electrophysiology; D005080:Exercise Test; D018737:Hand Strength; D006325:Heart Atria; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D013564:Sympathetic Nervous System / Q000502:physiology*; D013565:Sympatholytics / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D013565:Sympatholytics; D008734:Methoxyhydroxyphenylglycol; D000638:Amiodarone; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine