Epinephrine is routinely used during treatment of cardiac arrest. Administration may improve immediate resuscitation at the cost of long term survival. We hypothesized that epinephrine transiently increases aortic pressure, but decreases blood flow to the brain during cardiopulmonary resuscitation (CPR). Methods: Six anesthetized Yorkshire pigs (31±4 kg) underwent 1 minute of untreated ventricular fibrillation (VF), followed by 9 minutes of guideline based CPR with mechanical compressions, then defibrillation. Epinephrine (1 mg IV) was administered 1-3 times per pig (median 2.5) at ≥3 minute intervals. Hemodynamic parameters were measured continuously with a micromanometer in the abdominal aorta and a perivascular flow probe around the carotid artery. Results: After 10 minutes of VF, 5 of 6 pigs were successfully defibrillated, but all 5 became asystolic or lacked pulsatile aortic pressure 30 minutes after defibrillation. During CPR prior to epinephrine injection, aortic systolic and diastolic pressures were 72±26 and 17±3 mmHg respectively, coronary perfusion pressure was 15±5 mmHg and antegrade carotid blood flow was 141±77 mL/min. Epinephrine produced a repeatable, transient effect on both aortic pressure and carotid blood flow (see Table). Aortic systolic and diastolic pressures increased above pre-injection values with peak pressures reached approximately 80 seconds after injection and stabilizing after 180 seconds. Carotid flow decreased below pre-injection values with nadir flow reached approximately 80 seconds after injection, and remained below baseline for 100 additional seconds or longer. Conclusions: The effect of epinephrine on hemodynamics during CPR is not consistent over time. Epinephrine produces differential effects on aortic pressure and carotid flow. Although epinephrine may transiently improve coronary perfusion, it may do so at the cost of brain perfusion.