Abstract 273: Sildenafil and Beraprost Therapy Improve Arrhythmogenicity Through Connexin 43 Expression and Electrophysiological Property in Monocrotaline-Induced Rat Pulmonary Hypertension: Optical Mapping Analysis
Severe pulmonary hypertension (PH) is associated with sudden cardiac death (SCD). Optical mapping analysis (OMP) with electrophysiological study (EPS) and connexin-43 measures were performed weekly in Sprague-Dawley rat with monocrotaline (MCTi, 60 mg/kg) induced PH. Right ventricular pressure (RVP) and pulmonary vascular remodeling (PVR) were measured. EPS for ventricular fibrillation (VF) induction and RT-PCR for mRNA expression of connexin-43 (Conx-Ex) were performed. Daily administration of sildenafil (5 mg/kg) and beraprost (100 μg/kg) was initiated at 2 or 3 weeks after MCTi. OMP revealed abnormal RV conduction and action potential dispersion with high VF induction rate. Decreased Conx-Ex with high RVP at 3,4 and 5 weeks after MCTi were observed. Sildenafil with beraprost improved PVR, RV arrhythmogenicity, Conx-Ex, cardiac function (Table) and survival rates.
Conclusions: Sildenafil with beraprost therapy improves prognosis by preventing SCD and heart failure. These results give us further insights for understanding PH-induced SCD and therapeutic option for PH.
- © 2011 by American Heart Association, Inc.