Abstract 18389: Apamin Sensitive Current (IKCa ) Modulates Ventricular (but Not Atrial) Repolarization in Human Heart Failure
Altered myocyte electrophysiology in heart failure contributes to cardiac arrhythmias. In chronic human heart failure atrial repolarization is shortened while ventricular repolarization is prolonged. The calcium activated potassium (IKCa) current has been suggested as a novel atrial-selective pharmacologic target to modulate repolarization and arrhythmogenesis. We hypothesized that chamber-specific differences in IKCa current contribute to HF-induced repolarization changes.
Methods: End-stage failing hearts obtained at the time of transplant were used to isolate left ventricular (LV) midwall and left atrial appendage (LAA) myocytes. Action potential durations (APDs) were recorded at 0.5, 1 and 2 Hz before and after the application of 100nM apamin, an IKCa blocker.
Results: In LAA cells, apamin had no effect on APD50 or APD90 and no cellular arrhythmias (i.e. early afterdepolarizations, EADs) were observed. In the ventricular cells, apamin resulted in significant prolongation of the APD50 (p<0.05) and APD90 (p<0.05) at all rates; there was also a 40% increase in EADs, consistent with proarrhythmic potential.
Conclusions: In end-stage human HF, IKCa modulates LV repolarization and IKCa inhibition induces cellular arrhythmias. IKCa does not appear to modulate LAA myocyte electrophysiology in end-stage HF; our results do not support IKCa as a pharmacologic target for AF associated with heart failure. Potential explanations for the chamber-specific effects we observed include differential HF-induced alterations in APD, channel expression or calcium cycling. Thus, we suggest that inhibition of IKCa as a pharmacologic strategy in HF may be detrimental, as it may favor the initiation of triggered ventricular arrhythmias.
- © 2013 by American Heart Association, Inc.