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Objective: To determine whether selective aortic arch perfusion (SAAP) using serial infusions of oxygenated perflubron emulsion combined with aortic epinephrine (AoE) administration is more effective than conventional therapy in treating cardiac arrest., Methods: An experimental cardiac arrest model (10 min ventricular fibrillation and 2 min CPR) was used with 12 mixed-breed canines, randomized into 2 groups: control (n = 6), CPR and IV epinephrine, 0.01 mg/kg, at 12 min and then every 3 min; or AoE-SAAP (n = 6), CPR and aortic epinephrine, 0.01 mg/kg, at 12 min and then every 3 min, and serial SAAP with oxygenated 60% weight/volume (w/v) perflubron emulsion as follows: 300 mL over 30 sec at 12 min as continuous SAAP without CPR; 150 mL over 20-30 sec at 15 min and 18 min as pulsed diastolic SAAP during CPR., Results: AoE-SAAP resulted in increased coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) compared with control. CPR-diastolic (release phase) CPP during pulsed diastolic SAAP was similar to or greater in magnitude than the CPP generated during the initial SAAP infusion without CPR. ROSC for control was 0/6 and for AoE-SAAP was 4/6 (p < 0.05, Fisher's exact test). Time from initiation of CPR to ROSC with a sustained systolic aortic pressure > 60 mm Hg was 8.0 +/- 1.2 min in the 4 resuscitated AoE-SAAP animals., Conclusion: The combination of AoE with SAAP infusions of oxygenated perflubron emulsion was more effective than conventional resuscitation therapy. Pulsed diastolic SAAP is a promising method for performing SAAP.