Previous studies have shown that nitroglycerin (TNG) exerts beneficial electrophysiological effects in the setting of acute myocardial ischemia. To investigate the basis for these actions, the effects of TNG during coronary occlusion were studied in 19 anesthetized mongrel dogs. Refractory periods (obtained by extrastimulus method) and conduction times measured from local electrograms were determined in potentially ischemic and nonischemic areas prior to and after varying periods of occlusion of the left anterior descending coronary artery and following administration of TNG (300-400 mug intravenous bolus followed by an infusion titrated to reduce systolic blood pressure by 20 mm Hg). Following 15 minutes of occlusion, refractory periods in the ischemic zones shortened to 83% of control (P less than 0.001) resulting in a difference between refractory periods in the nonischemic and ischemic zones of 17.7%. After TNG administration this difference was decreased to 10.0% (P less than 0.001). However, with periods of occlusion of 60-90 min TNG did not significantly affect the difference of refractory periods. TNG had no significant effects on conduction times in nonischemic or ischemic areas. In six dogs, the effects of coronary occlusion and TNG on ventricular automaticity were examined by induction of complete heart block. The idioventricular rate and ventricular escape intervals after cessation of ventricular overdrive were used as indices of automaticity. Control idioventricular rates (62.5 +/- 3.7 beats/min) remained unchanged following both coronary occlusion (62.0 +/- 3.9) and TNG administration (60.7 +/- 3.2). Similarly, mean control escape intervals (1.84 +/- 0.2 sec) did not change after occlusion (1.78 +/- 0.3 sec) or TNG administration (1.86 +/- 0.2 sec). In conclusion, these observations suggest that 1) TNG enhances the electrical stability of the acutely ischemic myocardium by decreasing the difference of refractory periods between nonischemic and ischemic areas in the immediate period following occlusion, 2) since TNG has no significant effects on ventricular automaticity, its beneficial effects might be limited in suppression of arrhythmias of re-entrant origin.