Heterogeneity of ventricular fibrillation dominant frequency during global ischemia in isolated rabbit hearts

Introduction: Ventricular fibrillation (VF) studies show that ECG-dominant frequency (DF) decreases as ischernia develops. This study investigates the contribution of the principle ischernic metabolic components to this decline. Methods and Results: Rabbit hearts were Langendorff-perfused at 40 mL/min with Tyrode's solution and loaded with RH237. Epicardial optical action potentials were recorded with a photodiode array (256 sites, 15 x 15 mm). After 60 seconds of VF (induced by burst pacing), global ischernia was produced by low flow (6 mL/min), or the solution changed to impose hypoxia (95 % N-2/5% CO2), low pH(o) (6.7, 80 % O-2/20% CO2), or raised [K+](o) (8 mM). DF of the optical signals was determined at each site. Conduction velocity (CV), action potential duration (APD90), effective refractory period (ERP), activation threshold, dV/dt(max) and membrane potential were measured in separate experiments during ventricular pacing. During VF, ischernia decreased DF in the left ventricle (LV) (to [58 6] %, P < 0.001), but not the right (RV) ([93 5]%). Raised [K+]o reproduced this DF pattern (LV: [67 +/- 12]%, P < 0.001; RV: [95 91%). LV DF remained elevated in hypoxia or low pH,,. During ventricular pacing, ischernia decreased CV in LV but not RV. Raised [K+](o) did not change CV in either ventricle. Ischernia and raised [K+](o) shortened APD90 without altering ERP. LV activation threshold increased in both ischernia and raised [K+](o) and was associated with diastolic depolarization and decreased dV/dt(max),Conclusions: These results suggest that during VF, decreased ECG DF in global ischemia is largely due to elevated [K+](o) affecting the activation thresholds in the LV rather than RV.