Relation between cellular repolarization characteristics and critical mass for human ventricular fibrillation

Introduction: The critical mass for human ventricular fibrillation (VF) and its electrical determinants are unclear. The goal of this study was to evaluate the relationship between repolarization characteristics and critical mass for VF in diseased human cardiac tissues. Methods and Results: Eight native hearts from transplant recipients were studied. The right ventricle was immediately excised, then perfused (n = 6) or superfused (n = 2) with Tyrode's solution at 36°C. The action potential duration (APD) restitution curve was determined by an S₁-S₂ method. Programmed stimulation and burst pacing were used to induce VF. In 3 of 8 tissues, 10 μM cromakalim, an ATP- sensitive potassium channel opener, was added to the perfusate and the stimulation protocol repeated. Results show that, at baseline, VF did not occur either spontaneously or during rewarming, and it could not be induced by aggressive electrical stimulation in any tissue. The mean APD at 90% depolarization (APD₉₀) at a cycle length of 600 msec was 227 ± 49 msec, and the mean slope of the APD restitution curve was 0.22 ± 0.08. Among the six tissues perfused, five were not treated with any antiarrhythmic agent. The weight of these five heart samples averaged 111 ± 23 g (range 85 to 138). However, after cromakalim infusion, sustained VF (> 30 min in duration) was consistently induced. As compared with baseline in the same tissues, cromakalim shortened the APD₉₀ from 243 ± 32 msec to 55 ± 18 msec (P < 0.001) and increased the maximum slope of the APD restitution curve from 0.24 ± 0.11 to 1.43 ± 0.10 (P < 0.01). Conclusion: At baseline, the critical mass for VF in diseased human hearts in vitro is >111 g. However, the critical mass for VF can vary, as it can be reduced by shortening APD and increasing the slope of the APD restitution curve.