Although vasopressin increases vital organ blood flow during cardiopulmonary resuscitation (CPR), endocardial perfusion remains suboptimal. This study was designed to assess the effects of vasopressin versus a combination of vasopressin and nitroglycerin on vital organ blood flow in a porcine model of CPR. After 4 min of cardiac arrest, and 3 min of closed-chest compressions, 14 animals were randomly treated with either 0.4 U/kg vasopressin (n = 7) or 0.4 U/kg vasopressin combined with 5 microg/kg nitroglycerin (n = 7). Coronary and cerebral perfusion pressure as well as left ventricular myocardial blood flow was comparable between groups throughout the experiment. Ninety seconds after drug administration, vasopressin combined with nitroglycerin resulted in comparison with vasopressin alone in significantly higher mean (+/- standard error of the mean) left ventricular endocardial blood flow (78+/-7 vs 51+/-5 ml x min(-1) x 100 g(-1); P < 0.05), and a significantly higher endocardial/epicardial perfusion ratio (0.93+/-0.09 vs 0.57+/-0.06; P < 0.05). Seven of seven animals in the vasopressin group, and four of seven animals in the vasopressin and nitroglycerin group (NS) were resuscitated successfully and survived the 2-h observation period. We conclude that, when compared with vasopressin therapy alone, combined vasopressin and nitroglycerin improved endocardial perfusion significantly immediately after drug administration during CPR.