The influence of increasing left atrial pressures (0.5, 1.0, and 2.0 kPa) on the incidence of ventricular arrhythmias and the liberation of prelabeled norepinephrine (3H-NE) was investigated in the isolated working rat heart. Acute regional myocardial ischemia (30 min) was produced by ligature of the left main coronary artery with subsequent release of the ligature to achieve reperfusion, which consistently provoked ventricular arrhythmias. The magnitude of regional ischemia was measured by microspheres, and the efflux of 3H-labeled NE compounds was measured in the coronary effluent. Our data show that an increase in atrial pressure enhanced reperfusion arrhythmias, but the magnitude of NE release was not directly related to the occurrence of arrhythmias. It is proposed that increased heart work has an arrhythmogenic effect by enhancing the severity of regional ischemia.