Relaxin Suppresses Atrial Fibrillation by Reversing Fibrosis and Myocyte Hypertrophy and Increasing Conduction Velocity and Sodium Current in Spontaneously Hypertensive Rat Hearts

RATIONALE:Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly and hypertensive patients and has been correlated to enhanced atrial fibrosis. Despite a lack of direct evidence that fibrosis causes AF, reversal of fibrosis is considered a plausible therapy. OBJECTIVE:To evaluate the efficacy of the antifibrotic hormone relaxin (RLX) in suppressing AF in spontaneously hypertensive rats (SHR). METHODS AND RESULTS:Normotensive Wistar-Kyoto (WKY) and SHR were treated for 2 weeks with vehicle (WKY+V and SHR+V) or RLX (0.4 mg/kg per day, SHR+RLX) using implantable mini-pumps. Hearts were perfused, mapped optically to analyze action potential durations, intracellular Ca transients, and restitution kinetics, and tested for AF vulnerability. SHR hearts had slower conduction velocity (CV; P