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Positive atrial inotropic effect of dofetilide after cardioversion of atrial fibrillation or flutter

2000; Elsevier BV; Volume: 86; Issue: 6 Linguagem: Inglês

10.1016/s0002-9149(00)01044-4

1879-1913

Jeanne M. DeCara, Arthur Pollak, Simon W Dubrey, Rodney H. Falk,

Atrial Fibrillation Management and Outcomes

Dofetilide is a class III antiarrhythmic agent that selectively blocks the rapid component of the delayed rectifier current (Ikr). Blockade of Ikr prolongs the action potential, thereby lengthening the effective refractory period of cardiac tissue. 1 Gwilt M Arrowsmith J.E Blackburn K.J Burges R.A Cross P.E Dalrymple H.W Higgins A.J UK-68,798 a novel, potent and highly selective class III antiarrhythmic agent which blocks potassium channels in cardiac cells. J Pharmacol Exp Ther. 1991; 256: 318-324 PubMed Google Scholar It has been postulated that dofetilide’s drug-induced action potential prolongation alters intracellular calcium concentration, resulting in increased cardiac contractility. 2 Tande P.M Bjornstad H Yang T Refsum H Rate-dependent class III antiarryhthmic action, negative chronotropy, and positive inotropy of a novel Ik blocking drug, UK-68,798 potent in guinea pig but no effect in rat myocardium. J Cardiovasc Pharmacol. 1990; 16: 401-409 Crossref PubMed Scopus (168) Google Scholar Hemodynamic studies of dofetilide in animals demonstrate a modest positive inotropic effect in ventricular myocardium, and studies in humans suggest a similar trend. 2 Tande P.M Bjornstad H Yang T Refsum H Rate-dependent class III antiarryhthmic action, negative chronotropy, and positive inotropy of a novel Ik blocking drug, UK-68,798 potent in guinea pig but no effect in rat myocardium. J Cardiovasc Pharmacol. 1990; 16: 401-409 Crossref PubMed Scopus (168) Google Scholar , 3 Baskin E.P Serik C.M Wallace A.A Brookes L.M Selnick H.G Claremon D.A Lynch Jr, J.J Effects of new and potent methanesulfonanilide class III antiarrhythmic agents on myocardial refractoriness and contractility in isolated cardiac muscle. J Cardiovasc Pharmacol. 1991; 18: 406-414 Crossref PubMed Scopus (54) Google Scholar , 4 Wallace A.A Stupienski R.F Brookes L.M Selnick H.G Claremon D.A Lynch Jr, J.J Cardiac electrophysiologic and inotropic actions of new and potent methanesulfonanilide class III antiarrhythmic agents in anesthetized dogs. J Cardiovasc Pharmacol. 1991; 18: 687-695 Crossref PubMed Scopus (58) Google Scholar , 5 Hoffmeister H.M Beyer M.E Seipel L Hemodynamic effects of antiarrhythmic compounds intrinsic effects and autonomic modulation. Am J Cardiol. 1997; 80: 24G-30G Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Atrial systolic dysfunction frequently exists after cardioversion of atrial arrhythmias. d-l-Sotalol, a drug that exerts a negative inotropic effect on the ventricle, also aggravates postcardioversion atrial dysfunction. 6 Pollak A Falk R.H Aggravation of postcardioversion atrial dysfunction by sotalol. J Am Coll Cardiol. 1995; 25: 665-671 Abstract Full Text PDF PubMed Scopus (40) Google Scholar Beause of dofetilide’s potential for a positive inotropic effect, we sought to evaluate whether this drug could have a positive effect on the human atrium in the postcardioversion state.