Aim: This study is to clarify whether sildenafil, which is a selective inhibitor of the isoform 5 of the enzyme phosphodiesterase, improves macrocirculation or/and microcirculation during ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR) so as to improve outcomes of resuscitation. Methods: Sixteen female pigs were used. After anesthesia, the abdominal cavity was opened to observe the mesenteric microcirculation. Following the guidelines, we determined microvascular flow index, perfused vessel density and proportion of perfused vessels both for large(diameter >20 mu m) and small (diameter <20 mu m) microvessels. Sildenafil (0.5 mg/kg) or saline was given at 30 minutes before inducing VF. After 8 min VF, 4 min CPR was started and then defibrillation was attempted. Results: Compared with saline, sildenafil reduced the shocks and duration of CPR (all P < .05), and improved coronary perfusion pressure (CPP) during CPR and 24-hour survival (all P < .05). Sildenafil significantly improved microcirculatory parameters in large microvessel and decreased the lactic acid level during VF and CPR (all P < .05), but the differences in small microvessel were not significant (all P > .05). Microvascular flow index in both large and small microvessels were closely correlated to each other (r = 0.91, P < .01), and to CPP during CPR ([r = .88, P < .01] and [r = .70, P < .05], respectively). Conclusion: Sildenafil increases the success of resuscitation through improving macrocirculation and microcirculation during VF and CPR. There is a close relationship between microvascular flow and CPP during CPR. (C) 2015 Elsevier Inc. All rights reserved.