This clinical and experimental investigation was designed to delineate and compare the relative effects of sodium nitroprusside (NP) and nitroglycerin (TNG) on electrocardiographic ischemic injury following acute myocardial infarction in patients and following coronary artery occlusion in dogs. Accordingly, in ten patients with anterior acute myocardial infarction and ST-segment elevation stable for 60 min, the effects of NP (average 95 mug/min i.v.) and TNG (average 0.48 mg sublingually) were studied. The hemodynamic actions of NP and TNG were directionally similar. However, NP increased average ST-segment elevation (ST) by 2.0 +/- 0.2 mm, while TNG reduced ST by 1.4 +/- 0.4 mm. In order to clarify this disparity, coronary artery occlusions were carried out in 14 open-chest dogs. During control, NP and TNG time periods, epicardial electrograms were recorded and regional myocardial blood flow (RMBF) determined by the microsphere technique. Nitropruside increased ST-segment elevation from 4.6 +/- 0.6 to 5.7 +/- 0.6 mV (P less than 0.05) and reduced RMBF from 35 +/- 3 to 27 +/- 2 ml/min/100 g (P less than 0.01) in the ischemic zones. In contrast, TNG reduced ST-segment elevation from 4.9 +/- 0.7 to 3.0 +/- 0.7 mV (P less than 0.05), while increasing RMBF TO 43 +/0 4 ml/min/100 G (P less than 0.05) and the endo/epicardial ratio from 0.57 +/- 0.06 to 0.69 +/- 0.07 (P less than 0.01). Although TNG and NP exhibit similar hemodynamic effects, TNG reduced electrocardiographic ischemic injury, at least in part, by increasing perfusion of the ischemic areas and redistributing it favorably, while NP increased electrocardiographic ischemic injury, at least in part, by reducing perfusion. Therefore, TNG seems preferable to NP for reducing preload and afterload in patients during the early phase of acute myocardial infarction.