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

Wide-area low-energy surface stimulation of large mammalian ventricular tissue

The epicardial and endocardial surfaces of the heart are attractive targets to administer antiarrhythmic electrotherapies. Electrically stimulating wide areas of the surfaces of small mammalian ventricles is straightforward given the relatively small scale of their myocardial dimensions compared to the tissue space constant and electrical field. However, it has yet to be proven for larger mammalian hearts with tissue properties and ventricular dimensions closer to humans. Our goal was to address the feasibility and impact of wide-area electrical stimulation on the ventricular surfaces of large mammalian hearts at different stimulus strengths. This was accomplished by placing long line electrodes on the ventricular surfaces of pig hearts that span wide areas, and activating them individually. Stimulus efficacy was assessed and compared between surfaces, and tissue viability was evaluated. Activation time was dependent on stimulation strength and location, achieving uniform linear stimulation at 9x threshold strength. Endocardial stimulation activated more tissue transmurally than epicardial stimulation, which could be considered a potential target for future cardiac electrotherapies. Overall, our results indicate that electrically stimulating wide areas of the ventricular surfaces of large mammals is achievable with line electrodes, minimal tissue damage, and energies under the human pain threshold (100 mJ)