Verapamil prolongs atrial fibrillation by evoking an intense sympathetic neurohumoral effect.
BACKGROUND: Verapamil is an effective drug to slow ventricular rate in atrial fibrillation (AF). Clinically, however, i.v. 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, i.v. 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.
Friedman, HS; Rodney, E; Sinha, B; Sharafkhaneh, A; Wattanasuwan, N; Win, M; Mallipeddi, D; Sinha, A; Hussain, A; Dai, CP
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