Abstract 18452: IKca Current Contributes to Ventricular Repolarization During Chronic, Not Short-term, Heart Failure
Heart failure (HF) is a chronic disease that develops over months to years. In HF, ventricular repolarization is prolonged. We tested the hypothesis that IKCa modulates repolarization only when ventricular repolarization reserve is reduced as occurs in chronic HF, but not short term HF.
Methods: A tachypacing - induced HF canine model was used, and LV midwall myocytes were isolated from 1 and 4 month HF groups, and compared to normal controls. Action potential duration at 50 (APD50) and 90% (APD90) repolarization was measured before and after the application of 100nM apamin (IKCa blocker, n=5-9 per group). Adjacent tissue (n=4 per group) was collected to measure the proteins encoding cardiac IKCa (SK2 and SK3).
Results: One and 4 month HF had similar severity of HF (LVFS: 19.00 ± 1.36 vs. 15.9 ± 2.45, respectively P=NS). APD50 or APD90 in 1 month HF was no different from controls. 4 Mo HF resulted in a significant (P<0.05) APD90 prolongation compared to both control and 1 Mo HF groups, consistent with reduced repolarization reserve. Apamin significantly increased (P<0.05) APD50 and APD90 only in the 4 Mo HF group. Similarly proarrhythmic repolarization instability (beat-to-beat variability) was evident after apamin in the 4 month, but not the 1 month HF group (p<0.05).
SK2 expression was unchanged between groups; SK3 was increased ~ 4 fold in both 1 month and 4 month HF group (P<0.05 vs control).
Conclusions: Changes in SK protein expression do not fully explain IKCa -induced repolarization modulation. Rather, IKCa inhibition prolongs repolarization only when repolarization reserve is decreased, as occurs in chronic HF. The safety of targeting IKCa in chronic HF needs to be carefully evaluated as IKCa inhibition may increase susceptibility to ventricular arrhythmias.
- © 2013 by American Heart Association, Inc.