Figure 1: Schematic Representation of the Randomized 2 × 2 Protocol Including Epi and ECMO Randomization

Each experiment began with endovascular balloon occlusion of the ostial left anterior descending artery (LAD). If ventricular fibrillation (VF) did not occur spontaneously, it was induced electrically after 5 min. Ventilations were then halted and no treatment was provided for 5 min. High-quality cardiopulmonary resuscitation (CPR) was then initiated for 10 min of basic life support (BLS), representing first-responder CPR. Animals were then randomized to receive epinephrine (Epi) 0.5 mg intravenous or saline placebo every 5 min for the 35 min of advanced life support (ACLS). At minute 45 of CPR, the animals were again randomized into the CPR-facilitated group (no extracorporeal membrane oxygenation [NO ECMO]) or the ECMO+ group. In the NO ECMO group, the LAD balloon was deflated and resuscitation continued for up to 15 more min. If no return of spontaneous circulation (ROSC) was achieved, the animal was declared dead. If ROSC was achieved, the animal was maintained for 4 h. ECMO+ animals were cannulated for venoarterial ECMO followed by LAD balloon deflation and resuscitation continued. If ROSC was not achieved within 15 min, the animal was declared dead. If ROSC was achieved, the animal was maintained for 4 h, at which time it was assessed for suitability for decannulation. ECMO+ pigs meeting criteria for decannulation were maintained for 1 more hour, assessed again for decannulation criteria, and then sacrificed at hour 5.