Abstract 3080: Cardiac Resynchronization Therapy For Chronic Heart Failure Restores Action Potential Duration, Resting Potential And Inward Rectifier Current.
BACKGROUND: Cardiac resynchronization therapy (CRT) is non-pharmacologic treatment known to reduce morbidity and mortality in heart failure (HF) patients. The cellular mechanisms for the efficacy of CRT are poorly defined.
METHODS: We used a canine model of chronic HF (15 months of RV tachypacing to induce heart failure followed by 9 months of CRT, n=3) to study reverse remodeling of in vivo and myocyte function. An untreated group of HF (24 months HF, n=4), and a group of 3 normal dogs served as controls. Left ventricular midmyocardial myocytes were studied using perforated patch whole cell recordings at 36°C.
RESULTS: CRT reduced LV mass and improved functional capacity compared to the untreated HF group (p< 0.05), and normalized the Action Potential Duration (APD) at 50% (APD50) and 90% (APD90) repolarization (p<0.05). HF induced a depolarization of the resting membrane potential (RMP, p<0.03); CRT restored the RMP toward control values (Figure⇓). The changes in RMP are attributable to decreased inward IK1 in the HF group; inward IK1 was restored by CRT (Figure⇓). We observed the well-known HF-induced decrement in the transient outward K+ current (Ito); CRT had no effect of the HF-induced decrease in Ito.
CONCLUSIONS: These data suggest that Ito has no role in determining APD in canines. In our chronic HF model, CRT produces myocyte reverse remodeling, including restoration of the APD, the RMP, and inward IK1.