Objective: Previous studies have suggested that epinephrine reduces brain tissue O2 tension (PbtO2) after the return of spontaneous circulation (ROSC) via α1-adrenoceptor stimulation and that pralidoxime had α1-adrenoceptor inhibitory action together with non-adrenergic vasopressor action. We sought to investigate the effects of pralidoxime administered during cardiopulmonary resuscitation (CPR) as a sole vasopressor on PbtO2 after ROSC. We hypothesized that pralidoxime administration would lead to a comparable ROSC rate and a higher PbtO2 after ROSC when compared to epinephrine administration. Methods: After 7 minutes of ventricular fibrillation, 24 pigs randomly received either pralidoxime or epinephrine during CPR. Cerebral measurements, including PbtO2, were measured from the parietal cortices during the 60-minute post- ROSC period. Results: Coronary perfusion pressure (CPP) during CPR was significantly higher in the epinephrine group than in the pralidoxime group (P=0.012). All the animals in the epinephrine group achieved ROSC, while seven (58.3%) did so in the pralidoxime group (P=0.037). The area under the curves for PbtO2 during the post-ROSC period did not differ between the two groups. Conclusion: Pralidoxime alone was significantly inferior to epinephrine in increa...