Coronary perfusion pressure and its relation with the expired carbon dioxide concentration (end-tidal CO2) was examined in a rodent model of sustained ventricular fibrillation and subsequent cardiopulmonary resuscitation. Equipressor dosages of the pure alpha 1-agonist methoxamine, the mixed alpha/beta-agonists epinephrine and norepinephrine were randomly compared with 0.9% NaCl. Thirty two Sprague-Dawley rats were anesthetized and catheters were advanced into the aorta, right ventricle, right atrium and inferior vena cava. After 4 min of untreated ventricular fibrillation external chest compression was initiated and defibrillation was attempted after 8 min. Drugs were infused for 3 min during cardiopulmonary resuscitation into the inferior vena cava. A 60-min survival period followed methoxamine administration in 7 of 8 (P < 0.019 vs. NaCl), after epinephrine in 4 of 8, after norepinephrine in 5 of 8, and after NaCl in only 2 of 8 animals. Resuscitation success was determined by coronary perfusion and mean aortic pressures generated during cardiopulmonary resuscitation but not by arterial or venous blood gases. Adrenergic agents increased coronary perfusion and mean aortic pressures but decreased end-tidal CO2 which failed to correlate with these pressures. Accordingly, alpha-adrenergic agents mitigated the accuracy of end-tidal CO2 as a non-invasive hemodynamic monitor and predictor of survival after rodent cardiopulmonary resuscitation.