Ventricular arrhythmias are primarily responsible for sudden cardiac death early after the onset of acute myocardial ischemia. We designed an experimental model to simultaneously characterize regional myocardial function, myocardial blood flow, and electrophysiological parameters, and to determine predisposing factors for the development of early ventricular arrhythmias (EVA). The left circumflex coronary artery was occluded in six anesthetized (n = 2 piritramide/N2O, n = 4 chloralose/urethane) mongrel dogs. Systolic wall thickening (%WT) in a control zone and in the central ischemic zone was measured with sonomicrometry and regional myocardial blood flow (RMBF) with colored microspheres. Excitability and relative refractory period at the stimulus electrode and conduction times to all other electrodes were determined with a three-dimensional transmural multi(16)-electrode assay using a computer algorithm. In three of six dogs spontaneous EVA occurred 4 to 6 min after coronary occlusion, degenerating to ventricular fibrillation in two of these dogs. The three dogs developing EVA were not distinguished from those not developing EVA, neither by the kind of anesthesia nor by ischemic % WT (-6.6 +/- 3.8 [SD] vs -7.8 +/- 1.6, ns). Also, dogs with and without EVA did not differ significantly in excitability and relative refractory period. In contrast, dogs with EVA were characterized by a greater mass of severely ischemic myocardium, i.e., exhibiting a RMBF reduction to less than 0.1 ml/(min.g) (18 +/- 3 g vs 7 +/- 4 g, p less than 0.05), and by an increase in subendocardial conduction times of greater than 100% above the respective pre-ischemic values (120 +/- 18% vs 66 +/- 9%, p less than 0.05). Dogs with and without EVA were not as clearly distinguished by the increases in subepicardial (81 +/- 22% vs 46 +/- 15%, ns) and transmural (98 +/- 31% vs 67 +/- 14%, ns) conduction times. The development of EVA is associated with a greater mass of severely ischemic myocardium and a greater increase in subendocardial conduction times.