To improve the efficiency of standard cardiopulmonary resuscitation (CPR), we evaluated the potential value of impeding respiratory gas exchange selectively during the decompression phase of standard CPR in a porcine model of ventricular fibrillation. After 6 min of untreated cardiac arrest, anesthetized farm pigs weighing 30 kg were randomized to be treated with either standard CPR with a sham valve (n = 11) or standard CPR plus a functional inspiratory impedance threshold valve (ITV(TM)) (n = 11). Coronary perfusion pressure (CPP) (diastolic aortic minus right atrial pressure) was the primary endpoint. Vital organ blood flow was assessed with radiolabeled microspheres after 6 min of CPR, and defibrillation was attempted 11 min after starting CPR. After 2 min of CPR, mean +/- SEM CPP was 14 +/- 2 mm Hg with the sham valve versus 20 +/- 2 mm Hg in the ITV group (P < 0.006). Significantly higher CPPs were maintained throughout the study when the ITV was used. After 6 min of CPR, mean +/- SEM left ventricular and global cerebral blood flows were 0.10 +/- 0.03 and 0.19 +/- 0.03 mL. min(-1). g(-1) in the Control group versus 0.19 +/- 0.03 and 0.26 +/- 0.03 mL. min(-1). g(-1) in the ITV group, respectively (P < 0.05). Fifteen minutes after successful defibrillation, 2 of 11 animals were alive in the Control group versus 6 of 11 in the ITV group (not significant). In conclusion, use of an inspiratory impedance valve during standard CPR resulted in a marked increase in CPP and vital organ blood flow after 6 min of cardiac arrest.