Several animal studies have demonstrated an improvement in cerebral blood flow (CBF) and myocardial blood flow (MBF) after the administration of epinephrine (E) 0.20 mg/kg during closed chest CPR. The administration of norepinephrine (NE) in doses of 0.12 and 0.16 mg/kg demonstrated a trend toward improved CBF and MBF during CPR over that seen with E 0.20 mg/kg in the same animal model. The purpose of this study was to compare the effects of a higher dose of NE 0.20 mg/kg to E 0.20 mg/kg to determine if increasing doses of NE would demonstrate further improvement in CBF and MBF during CPR. Fourteen immature swine were anesthetized and instrumented for regional blood flow and hemodynamic measurements. After 10 min of ventricular fibrillation (VF), CPR was begun using a mechanical thumper. After 3 min of CPR, the animals received either E 0.20 mg/kg (n = 7) or NE 0.20 mg/kg (n = 7) through a right atrial catheter. CPR was continued for an additional 3.5 min and defibrillation was then attempted. CBF (ml/min/100 g), MBF (ml/min/100 g), myocardial oxygen delivery (MDo2; ml O2/min/100 g), myocardial oxygen consumption (MVo2; ml O2/min/100 g), and myocardial oxygen extraction ratios (ER, MVo2/MDo2) were measured during normal sinus rhythm (NSR), during CPR, and during CPR following drug administration. Following drug administration, CBF, MBF, MDo2 and MVo2 rose while ER fell in both E and NE groups. There were no significant differences between groups in CBF, ER, or intravascular pressures following drug administration (P greater than or equal to 0.07). The NE group demonstrated significantly higher MBF (118.9 +/- 73.1 vs. 62.2 +/- 45.3, P = 0.04), MVo2 (14.2 +/- 7.7 vs. 7.0 +/- 3.8, P = 0.05), and MDo2 (19.9 +/- 13.4 versus 9.4 +/- 6.3, P = 0.05) compared to the E group following drug administration While NE improved MBF and MDo2 over E during CPR, there was a trend toward lower resuscitation rates with NE (57.1% vs. 85.7% P = 0.56). Any benefit of higher MBF and MDo2 with NE 0.20 mg/kg appears to be offset by proportionately high MVo2 and a trend toward lower resuscitation rates in the NE 0.20 mg/kg animals.