OBJECTIVE To describe a new method of CPR that optimizes vital organ perfusion pressures and carotid blood flow. We tested the hypothesis that a combination of high dose sodium nitroprusside (SNP) as well as non-invasive devices and techniques known independently to enhance circulation would significantly improve carotid blood flow (CBF) and return of spontaneous circulation (ROSC) rates in a porcine model of cardiac arrest. METHODS 15 isofluorane anesthetized pigs (30±1 kg), after 6 min of untreated ventricular fibrillation, were subsequently randomized to receive either 15 min of standard CPR (S-CPR) (8 animals) or 5 min epochs of S-CPR followed by active compression-decompression (ACD)+inspiratory impedance threshold device (ITD) CPR followed by ACD+ITD+abdominal binding (AB) with 1mg of SNP administered at minutes 2, 7, 12 of CPR (7 animals). Primary endpoints were CBF and ROSC rates. ANOVA and Fisher's exact test were used for comparisons. CONCLUSIONS There was significant improvement in the hemodynamic parameters in the SNP animals. ROSC was achieved in 7/7 animals that received SNP and in 2/8 in the S-CPR (p=0.007). CBF and end tidal CO(2) (ETCO(2)) were significantly higher in the ACD+ITD+AB+SNP (SNPeCPR) animals during CPR. Bolus doses of SNP, when used in conjunction with ACD+ITD+AB CPR, significantly improve CBF and ROSC rates compared to S-CPR.