AMIODARONE CAUSES ENDOTHELIUM-DEPENDENT VASODILATION IN HUMAN HAND VEINS IN-VIVO

Objective: Amiodarone, a class III antiarrhythmic agent, is a potent c oronary vasodilator. However, direct evidence for its vasodilatory eff ects in human vasculature in vivo is not available. The aim of the stu dy was to investigate the short-term effects of amiodarone in preconst ricted human hand veins and to explore the underlying mechanisms. Meth ods: Thirty-one healthy male volunteers were studied with use of the d orsal hand vein compliance technique. The hand veins of the subjects w ere preconstricted with the alpha(1)-adrenergic receptor agonist pheny lephrine, and amiodarone, inhibitors of nitric oxide formation (N-G-mo nomethyl-L-arginine, L-NMMA), and adenosine triphosphate-dependent pot assium channels (glyburide [INN, glibenclamide]) were infused in the p resence or absence of a cyclooxygenase inhibitor (acetylsalicylic acid ), and the venodilator effect was measured. Furthermore, amiodarone wa s infused in prostaglandin F-2 alpha (dinoprost)preconstricted hand ve ins. Results:Amiodarone produced dose-dependent venodilation (51% +/- 3% maximum). Maximum amiodarone-induced venodilation was lower in dino prost compared with phenylephrine-preconstricted veins. Pretreatment w ith acetylsalicylic acid reduced the amiodarone-induced venodilation b y 40% +/- 6%. L-NMMA reduced the amiodarone-induced venodilation after pretreatment with acetylsalicylic acid by 72% +/- 3%. Glyburide decre ased the venodilatory response of amiodarone by 31% +/- 11%, whereas o nly a slight but not statistically significant additional reduction in venodilation was detected after pretreatment with acetylsalicylic aci d. Infusion of the solvents of commercially available amiodarone (poly sorbate 80 and benzyl alcohol) did not cause vasodilation in phenyleph rine-preconstricted veins. Conclusions: Amiodarone dilates preconstric ted human hand veins in vivo and acts as a venodilator through the cyc looxygenase pathway, activation of nitric oxide synthase, and blockade of alpha-adrenergic mechanisms.