Nitroglycerin reduces ischemic injury during acute myocardial infarction (AMI) in dogs — an effect that is potentiated when drug-induced hypotension and tachycardia are prevented with phenylephrine. To determine the effectiveness of nitroglycerin, alone or with phenylephrine, during AMI in man, 12 patients (five of whom had left heart failure) were evaluated by summing ST-segment abnormalities (σST) from 35 precordial electrodes. The seven patients without heart failure did not benefit consistently from nitroglycerin alone; however, addition of phenylephrine to abolish nitroglycerin-induced arterial pressure reduction uniformly diminished σST(4.9 to 3.2 mv; P < 0.05). In patients with heart failure, nitroglycerin alone consistently reduced ischemia (5.8 to 4.4mv, P < 0.05); addition of phenylephrine often partially reversed this effect. Thus, administration of nitroglycerin, alone or with phenylephrine, can reduce myocardial ischemic injury during AMI in man; however, the response to phenylephrine depends on the presence or absence of left ventricular failure before treatment. (N Engl J Med 293:1008–1012,1975)