Simulated interactions between a Class III antiarrhythmic drug and a figure 8 reentry.

Ventricular Fibrillation is responsible for a majority of sudden cardiac death, but little is known about how ventricular tachycardia (VT) degenerates into ventricular fibrillation. Several clinical studies focused only on preventing VT with a class III antiarrhythmic drug resulted in many deaths. Our simulations investigate the interactions between an antiarrhythmic drug likely to suppress a VT and a Figure 8 reentry. A parameter AAR is introduced to increase the action potential duration and therefore simulate various Class III drugs. Simulations are ran under several conditions (phases of the reentry, values of AAR, durations). They show that a VT can be suppressed whatever the phase of the reentry but it strongly depends on the duration of the effect. It confirms that a drug which can suppress a reentry can also worsen it. It also shows a great variety of activation patterns and thus the complexity of antiarrhythmic drugs effects. Simulations also demonstrate that suppressing VT is an increasing function of AAR.

Role of the dispersion of refractoriness on cardiac reentries.

We used computer simulation to study the possible role of the dispersion of cellular coupling, refractoriness or both, in the mechanisms underlying cardiac arrhythmias. Local ischemia was first assumed to induce cell to cell dispersion of the coupling resistance (case 1), refractory period (case 2), or both (case 3). Our numerical experiments based on the van Capelle and Durrer model showed that vortices could not be induced. On the other hand, with cellular properties dispersed in a patchy way within the ischemic zone, a single activation wave could give rise to abnormal activities. This demonstrates the stability of the wave front under small inhomogeneities. Probabilities of reentry, estimated for the three cases cited above showed that a severe alteration of the coupling resistance may be an important factor in the genesis of reentry. Moreover, use of isochronal maps revealed that vortices were both stable and sustained with an alteration of the coupling alone or along with a reduction of the action potential duration. Conversely, simulations with reduction of the refractoriness alone, inducing only transient patterns, could exhibit functionally determined reentries.

Incidence of dispersion of refractoriness and cellular coupling resistance on cardiac reentries and ventricular fibrillation.

We used computer simulations to study the possible role of the dispersion of cellular coupling, refractoriness or both, in the mechanisms underlying cardiac arrhythmias. Local ischemia was first assumed to induce cell to cell dispersion of the coupling resistance (Case 1), refractory period (Case 2), or both of them (Case 3). Our numerical experiments based on the van Capelle and Durrer model showed that vortices could not be induced by cell to cell variations. With cellular properties dispersed in a patchy way within the ischemic zone, a single activation wave could give rise to abnormal activities. This demonstrates the stability of the wave front under small inhomogeneities. Probabilities of reentry, estimated for the three cases cited above showed that a severe alteration of the coupling resistance may be an important factor in the genesis of reentry. Moreover, use of isochronal maps revealed that vortices were both stable and sustained with an alteration of the coupling alone or combined with a reduction of the action potential duration. Conversely, simulations with reduction of the refractoriness alone, inducing only transient patterns, could exhibit functionally determined reentries.