Abstract 187: Reduced Rapid Delayed Rectifier (IKr) and Inward Rectifier Current (IK1) Contribute Action Potential Prolongation and Diastolic Depolarization in a Chronic Canine Heart Failure Model
Heart Failure (HF) produces prolongation of the action potential duration (APD). Since human HF is a chronic syndrome, we used a chronic canine HF model to study HF-induced changes in K+ currents and action potentials (APs). METHODS: Right ventricular tachypacing (5–24 months) was used to induce heart failure with increases in QRS Amplitude, QRS widening, Left Ventricular (LV) Mass, and LV dimensions. LV myocytes were isolated from lateral mid-myocardial wall; perforated whole cell patch clamp was done at 36°C. RESULTS: The AP duration was significantly prolonged in the HF dogs compared to controls (Panel A). Chronic HF produced a large reduction in the transient outward K+ current (Ito) (10.7±1pA/pF (Control) vs. 1.8±0.7pA/pF (HF)). Inward rectifier K+ current (IK1) inward conductance and peak outward IK1 were significantly reduced in HF (p<0.05). The rapid component of the delayed rectifier (IKr) was significantly reduced with chronic HF (Panel B). Chronic HF did not alter the slow component of the delayed rectifier current (IKs, p=NS). CONCLUSIONS: In chronic canine non-ischemic cardiomyopathy, the large reductions in IK1, Ito and IKr cause diastolic depolarization and AP prolongation. These alterations may contribute to ventricular tachyarrhythmias during chronic nonischemic HF.