Clin Res Cardiol 101, Suppl 1, April 2012

P699 - Ranolazine suppresses atrial fibrillation in an experimental model of chronic heart failure due to development of atrial postrepolarization refractoriness and slowing of conduction velocity
P. Milberg1, G. Frommeyer2, M. Schmidt2, L. Eckardt1
1Department für Kardiologie und Angiologie, Universitätsklinikum Münster, Münster; 2Department für Kardiologie und Angiologie, Abteilung für Rhythmologie, Universitätsklinikum Münster, Münster;
Background: In a recent study, ranolazine (RAN) was reported to be effective and safe in converting atrial fibrillation (AF) to sinus rhythm by intake of a single dose (“pill in the pocket”) in patients with structural cardiac abnormalities. The apparent electrophysiologic safety and the ability to use it in patients where other Na+ channel blockers are contraindicated could have enormous economic implications. This is the first experimental study that identifies possible underlying mechanisms for the antiarrhythmic benefit of RAN application in chronic heart failure (CHF).
Methods and results: In 7 female rabbits CHF was induced by 4 weeks of rapid ventricular pacing leading to a significant decrease in ejection fraction. 12 rabbits were sham-operated and served as controls. Isolated failing and sham hearts were perfused using the Langendorff method and were paced with cycle lengths from 350 to 150ms in the atrium. In addition, burst pacing was used to induce atrial fibrillation. Two monophasic action potential recordings on the left- and two on the right epicardium showed an increase of atrial action potential duration (aAPD) and effective refractory period (aERP) in CHF hearts as compared with controls. Additional infusion of acetycholine (1µM) and isoproterenol (1µM) led to AF in all failing- and in 11 sham hearts. Simultaneous infusion of RAN (10µM) suppressed AF in 55% of sham- and 57% of failing hearts. RAN had no effect on aAPD but led to a significant increase of aERP (sham: +28ms; CHF: +24ms) leading to marked increase of atrial postrepolarization refractoriness (aPRR; ), defined as the difference of aERP and aAPD. Moreover, RAN application significantly increased conduction velocity in sham (+14ms) - and failing (+16ms) hearts, respectively.
In the present study, administration of RAN has been shown to be effective in suppressing AF not only in sham- but also in failing hearts. The antiarrhytmic effect is due to development of aPRR and a marked effect on conduction velocity. RAN might be a new safe option to reduce the burden of AF in CHF, where other antiarrhythmic drugs are contraindicated. The described electrophysiologic mechanism should be adopted as a fascinating novel antiarrhythmic option in heart failure.
Clin Res Cardiol 101, Suppl 1, April 2012
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-012-1100-6