Verapamil prolongs atrial fibrillation by evoking an intense sympathetic neurohumoral effect

Howard S. Friedman, Evans Rodney, Bindeshwari Sinha, Amir Sharafkhaneh, Norrapol Wattanasuwan, Moethu Win, Dayaker Mallipeddi, Anjan Sinha, Akhtar Hussain, Chen Pu Dai

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18 Scopus citations


Background: Verapamil is an effective drug to slow ventricular rate in atrial fibrillation (AF). Clinically, however, IV verapamil enhances AF despite experimental evidence suggesting favorable effects of the drug on AF-induced electrical remodeling of the atria. Methods and Results: To clarify this controversy, IV verapamil's effects were determined in 41 anesthetized dogs, including 6 after beta-blockade. Intravenous verapamil (0.20 mg/kg, bolus, and 0.20 mg/kg/h, infusion) increased the duration of AF (induced by a single extrastimulus), from 19 ± 6 to 130 ± 24 s, P<0.001, and slowed its ventricular response, from 246 ± 25 to 110 ± 15 min-1, P<0.001. Mean aortic pressure, P=0.002, and systemic vascular resistance, P<0.035, decreased, and mean right atrial pressure increased, P<0.001. Plasma norepinephrine concentration increased by 502 ± 83 pg/mL, P<0.001, plasma epinephrine concentration by 804 ± 206 pg/mL, P=0.002, and plasma total catecholamine concentration by 1606 ± 366 pg/mL, P=0.001. Prolongation of AF was related to an increase in mean right atrial pressure, R=0.49, P=0.014, right atrial wall tension, R=0.45, P=0.044, and plasma norepinephrine concentration, R=0.83, P<0.001, with plasma norepinephrine concentration remaining as an independent predictor of AF lengthening on multivariable analysis. In the presence of beta-blockade, verapamil produced comparable or more exaggerated hemodynamic effects, but it did not promote AF. Conclusion: The prolongation of AF by verapamil can be related directly to the intense sympathetic neurohumoral effect that occurs following the drug's administration.

Original languageEnglish (US)
Pages (from-to)293-303
Number of pages11
JournalJournal of Investigative Medicine
Issue number6
StatePublished - Jul 1999
Externally publishedYes


  • Antiarrhythmia agents
  • Atrial fibrillation
  • Calcium channel antagonist
  • Catecholamines
  • Electrophysiology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Friedman, H. S., Rodney, E., Sinha, B., Sharafkhaneh, A., Wattanasuwan, N., Win, M., Mallipeddi, D., Sinha, A., Hussain, A., & Dai, C. P. (1999). Verapamil prolongs atrial fibrillation by evoking an intense sympathetic neurohumoral effect. Journal of Investigative Medicine, 47(6), 293-303.