Ventricular activation during sympathetic imbalance and its computational reconstruction

We characterized the epicardial activation sequence during a norepinephrine (NE)-induced ventricular arrhythmia in anesthetized pigs and studied facto rs that modulated it. Subepicardial NE infusion caused the QRS complex to i nvert within a single beat (n = 35 animals, 101 observations), and the earl iest epicardial activation consistently shifted to the randomly located inf usion site (n = 14). This preceded right atrial activation, whereas the tot al ventricular epicardial activation time increased from 20 +/- 4 to 50 +/- 9 ms (P < 0.01). These events were accompanied by a ventricular tachycardi a and a drop in left ventricular pressure, which were fully reversed after the infusion was stopped. Epicardial pacing at the infusion site mimicked a ll electrical and hemodynamic changes induced by NE. The arrhythmia was pre vented by propranolol and abolished by cardiac sympathetic or vagal nerve s timulation. Focal automaticity was computationally reconstructed using a tw o-dimensional sheet of 256 x 256 resistively coupled ventricular cells, whe re calcium handling was abnormally high in the central region. We conclude that adrenergic stimulation to a small region of the ventricle elicits trig gered automaticity and that computational reconstruction implicates calcium overload. Interventions that reduce spatial inhomogeneities of intracellul ar calcium may prevent this type of arrhythmia.