A single stationary mother rotor, located in the fastest activating region and giving rise to activation fronts that propagate throughout the remainder of the myocardium, has been hypothesized to be responsible for the maintenance of ventricular fibrillation (VF). Others have reported a mother rotor in guinea pigs and rabbits. We wanted to see if a mother rotor exists in a larger heart, that is, pigs. Epicardial mapping studies have demonstrated that VF wavefronts in pigs tend to propagate from the posterior basal LV to the anterior LV and on to the anterior RV, raising the possibility of a mother rotor in the posterior LV. However, no sustained reentry consistent with a mother rotor was found on the posterior LV epicardium, even though an intramural mapping study showed that the fastest activating transmural layer was near the epicardium. Many wavefronts in the posterior LV entered the mapped region from the posterior boundary of the mapping array, adjacent to the posterior descending coronary artery, raising the possibility that a mother rotor is located in the right ventricle or septum. Since a previous study has shown that the RV activates more slowly than the LV during VF, the more likely site for a mother rotor was the septum. However, we then performed a study in which we recorded from the right side of the septum and found that reentry was uncommon there also and that the activation rate was slower than the posterobasal LV. Many of the VF wavefronts in the septum passed from the posterior septum toward the anterior septum. This fact coupled with the fact that many wavefronts passed from the posterior LV free wall toward the anterior LV free wall point to the region where the posterior free wall intersects with the septum, the region where the posterior papillary muscle is located, as the possible site of a mother rotor. Indeed, a recent abstract by others reports that, after propranolol, a stable reentrant circuit is present on the endocardium at the insertion of the posterior papillary muscle into the LV free wall in pigs.
DAD Inhibitor Improves Defibrillation. Introduction: Electrical and optical mapping studies of defibrillation have demonstrated that following shocks of strength near the defibrillation threshold (DFT), the first several postshock cycles always arise focally. No immediate postshock reentry was observed. Delayed afterdepolarizations (DADs) have been suggested as a possible cause of this rapid repetitive postshock activity. The aim of this study was to test the hypothesis that DFT is decreased by application of a DAD inhibitor. Methods and Results: Six pigs (30–35 kg) were studied. First, control DFT was determined using a three‐reversal up/down protocol. Each shock (RV‐SVC, biphasic, 6/4 msec) was delivered after 10 seconds of ventricular fibrillation (VF). Then, flunarizine (a DAD inhibitor) was injected intravenously (2 mg/kg bolus and 4 mg/kg/hour maintenance) and the DFT was again determined. A third DFT was determined 50 minutes after drug infusion was terminated to allow the drug to wash out. DFT after flunarizine application (520 ± 90 V, 14 ± 3 J) was significantly lower than control DFT (663 ± 133 V, 23 ± 4 J) . After the drug washed out, DFT (653 ± 107 V, 22 ± 4 J) returned to the control DFT value (P = 0.6) . Flunarizine reduced the DFT ∼22% by leading‐edge voltage and ∼40% by energy. Conclusion: Flunarizine, a DAD inhibitor, significantly improved defibrillation efficacy. This finding suggests that DADs could be the source of the rapid repetitive focal activation cycles arising after failed near‐DFT shocks before degeneration back into VF. Future studies are needed to investigate the cause of the earliest postshock activation and to determine if the DADs are responsible.
Introduction: The relative importance of nonuniform dispersion of refractoriness, steep restitution slopes, and anatomic heterogeneities in causing conduction block during ventricular fibrillation (VF) remains unknown. Methods and Results: In six open‐chest pigs, ventricular refractoriness and restitution curves were estimated from activation recovery intervals (ARIs) calculated from 504 (21 × 24) unipolar electrode recordings 2 mm apart in a plaque sutured to the left ventricular (LV) free wall. A steady‐state restitution protocol was performed twice at each of two pacing sites: the LV base and near the left anterior descending artery. VF was electrically induced four times and the incidence of conduction block at each electrode during the first 20 seconds was determined by an automated algorithm. The gradient of the ARI was calculated at each electrode to estimate the spatial dispersion of refractoriness. An exponential curve was fit to the restitution plots of ARIs versus the corresponding diastolic intervals (DIs) for all pacing cycle lengths at each electrode. The locations of epicardial blood vessels were noted after the study. Spatial patterns of conduction block were significantly correlated between the four VF episodes in the same animal (r = 0.66 ± 0.07, P < 0.05). At the shortest pacing cycle length, the spatial distribution of ARIs, ARI gradients, and restitution slopes was not random but formed clusters of similar values. However, none of these variables was significantly correlated with the incidence of conduction block, even though ARI gradients >2 msec/mm were present between many clusters and ∼90% of restitution slopes were >1. Instead, conduction block frequently appeared to cluster along epicardial vessels. Conclusion: Neither the dispersion of refractoriness nor action potential duration restitution determined during rapid pacing by itself is the major determinant of the location of conduction block during early VF in normal pigs. It may be that these factors interact synergistically with each other as well as with other factors, including anatomic heterogeneities such as those caused by blood vessels, which may be particularly important for the formation of conduction block and maintenance of VF.
The distribution of the transmembrane potential along an infinite strand of cardiac cells generated by a point source under steady-state conditions has been calculated using the asymptotic analysis method. With the intracellular conductivity changing periodically in space, the problem can be treated as dependent upon two variables: the large scale variable x covering the whole strand, and the small scale variable y defined on the unit cell. The solution is given as a two-scale expansion in powers of the period length. Each term of the expansion can be determined by solving the differential equations derived by decomposing the original problem. These equations do not have to be solved simultaneously; moreover, the linearity of the problem allows the separation of the x and y dependence in the higher order terms. The series converges quickly, and for all practical purposes, the solution containing zero-, first-, and second-order terms has a negligible truncation error. The subsequent terms of the solution have the following physiological interpretation: The zero-order term is the solution to the classical core-conductor model obtained by the homogenization of the periodic model, the first-order term acts as the dipole sources located at junctions, and finally, the second-order term resembles the monopole sources arising at junctions.
Background Understanding the mechanisms that drive ventricular fibrillation is essential for developing improved defibrillation techniques to terminate ventricular fibrillation (VF). Distinct organization patterns of chaotic, regular, and synchronized activity were previously demonstrated in VF that persisted over 1 to 2 minutes (long-duration VF [LDVF]). We hypothesized that activity on the endocardium may be driving these activation patterns in LDVF and that unsuccessful defibrillation shocks may alter activation patterns. Methods and Results The study was performed using a 64-electrode basket catheter on the left ventricle endocardium and 54 6-electrode plunge needles inserted into the left ventricles of 6 dogs. VF was induced electrically, and after short-duration VF (10 seconds) and LDVF (7 minutes), shocks of increasing strengths were delivered every 10 seconds until VF was terminated. Endocardial activation patterns were classified as chaotic (varying cycle lengths and nonsynchronous activations), regular (highly repeatable cycle lengths), and synchronized (activation that spreads rapidly over the endocardium with diastolic periods between activations). Conclusions The results showed that the chaotic pattern was predominant in early VF, but the regular pattern emerges as VF progressed. The synchronized pattern only emerged occasionally during late VF. Failed defibrillation shocks changed chaotic and regular activation patterns to synchronized patterns in LDVF but not in short-duration VF. The regular and synchronized patterns of activation were driven by rapid activations on the endocardial surface that blocked and broke up transmurally, leading to an endocardial to epicardial activation rate gradient as LDVF progressed.
