Mechanism of Procainamide-Induced Prevention of Spontaneous Wave Break During Ventricular Fibrillation

Abstract

Background-Ventricular fibrillation (VF) is maintained by 2 mechanisms: first by reentry formation and second by spontaneous wave break or wave splitting. We hypothesized that spontaneous wave break results from a critical shortening of the action potential duration (APD) during VF and that its prevention by procainamide eliminates spontaneous wave break. Methods and Results-The endocardial surfaces of 7 isolated, perfused swine right ventricles were mapped with a 3.2ϫ3.8 cm plaque with 477 bipolar electrodes. Activation pattern during VF was visualized dynamically while simultaneously recording epicardial action potentials with a glass microelectrode. APD restitution curves were constructed during VF (dynamic) and during S 1 S 2 protocols. At baseline, VF was maintained by 5.3Ϯ1 wavelets. Procainamide (PA) at 10 g/mL decreased the number of wavelets to 3.5Ϯ1 (PϽ0.05). At baseline VF was maintained by spontaneous wave break and by new reentrant wave front formation. PA eliminated spontaneous wave break during VF while having no effect on reentry formation. PA increased the cycle length of the VF (148.5Ϯ41.2 ms vs 81Ϯ10 ms, PϽ0.01) and the core area of the reentry from 5.8 to 14.5 mm 2 (PϽ0.05). Dynamic APD restitution curve during VF showed that PA eliminated the initiation of activation with APDs shorter than 30 ms. The effects of PA on cellular properties and wave front dynamics were reversed during 60 minutes of drug-free perfusion. Conclusions-Critically

Rectification of the Background Potassium Current

“…Thus, the two papillary muscles in the LV of the guinea pig heart, which insert in the LV apex and anterior LV wall, may conceivably help to stabilize the rotor. However, in contrast to the experiments of Kim et al 24 in which reentry was often terminated by the other wavelets that existed during VF, we observed that the reentrant source remains stable within the field of view as long as 150 rotations, at least in one case (Figure 3). Nevertheless, as 3-dimensional scroll waves are predicted to align their filaments according to the myocardial fibers, 13 we cannot rule out the possibility that structures in the LV may somehow stabilize the reentrant circuit.…”

“…Kim et al 24 suggested that source-sink mismatch between a papillary muscle and the ventricular wall may serve to anchor the rotor. Thus, the two papillary muscles in the LV of the guinea pig heart, which insert in the LV apex and anterior LV wall, may conceivably help to stabilize the rotor.…”

Spiral Wave Attachment to Millimeter-Sized Obstacles

“…Its effects include decreased excitability, 28 slowing of conduction and formation of conduction block, 28 -30 increase in refractoriness or refractory gradient, 30 -32 and oscillation in RCL. 30 Sodium channel blockers have been shown to increase the core size [33][34][35] and pivoting radius 14 of the spiral wave, and the present results suggest that lidocaine facilitates the partial or complete detachment of waves anchored to small obstacles so that they are no longer stationary. Partial detachment results in an increase in tip path length that augments the slowing effect of lidocaine on CV to produce an increase in CL.…”

Mechanisms of Atrial Fibrillation Termination by Pure Sodium Channel Blockade in an Ionically-Realistic Mathematical Model

“…The effects of I Na inhibition on activation during VF are qualitatively similar to those on AF, including increased organization with slowing and enlargement of re-entrant rotors. 31,43 However, the ventricular mass is much greater than that of the atrium, potentially making it much more difficult to enlarge rotors beyond the spatial capacity of ventricular tissue. In addition, boundary conditions are much more plentiful in the atria than the ventricles, making spiral core drift to a boundary much more likely at the atrial level.…”