Abstract 211: Blockade of Na+-Sensitive K+ Channels Alleviates Frequency-Dependent Electrical Failure in an Ex-Vivo Model of VF-Induced Cardiac Arrest
Ventricular fibrillation (VF), global ischemia and beta-adrenergic stimulation form the common context of sudden cardiac arrest. Regional and global loss of excitability under these conditions sets the stage of resuscitation failure due to either asystole or post-reperfusion VF recurrence. We hypothesized that Na+-sensitive K+ current (IKNa) significantly contributes to electrical failure under combined conditions of ischemia, high excitation frequency, and beta-adrenergic stimulation. We performed optical mapping of voltage-sensitive dye RH237 in the anterior right and left ventricle (RV and LV) of Langendorff-perfused rabbit hearts subjected to normothermic global no-flow ischemia, isoproterenol (30 nM) and pacing at the cycle length (CL) of either 300 ms or 200 ms. 2,3-butanedione monoxime (20 mM) was used to reduce motion artifact. Excitable area was measured in optical maps based on the criterion of the minimum time-derivative of the upstroke of the optical action potential. Decrease of the pacing CL from 300 to 200 ms dramatically accelerated loss of excitability in both RV and LV (Figure, p<0.0001). Treatment with IKNa blocker R56865 significantly postponed frequency-dependent electrical failure (p<0.0001), the protective effect being larger in RV than in LV (see Figure). After 5 min of reperfusion, R56865 treatment group also showed better recovery of excitability, effect being predominant in the LV in comparison to 200 ms CL group. This is the first study to show that IKNa activation can promote electrical failure under conditions mimicking VF-induced cardiac arrest.
- © 2013 by American Heart Association, Inc.