BACKGROUND: The purpose of this paper was to evaluate myocardial and pulmonary effects of aqueous oxygen (AO) delivered directly into the pulmonary circulation in acute hypoxia. METHODS: Six calves (2 months old, 68.0 +/- 2.2 kg) after general anesthesia, mechanical ventilation, and median sternotomy underwent total right heart bypass using fixed flow with continuous pressure and blood gas measurements in carotid and femoral arteries, left atrium, the coronary sinus and PA. Measurements of systemic and PA pressures and O2 saturations; myocardial O2 atrioventricular (AV) differences; and O2 extraction were made. After base line measurements, hypoxic ventilation reducing the mean arterial PO2 from 277 +/- 102 mm Hg to 47 +/- 4 mm Hg (p < 0.0005) was maintained for 30 minutes. Without changes in the hypoxic ventilation (mean arterial PO2 = 49 +/- 11 mm Hg) 3 ml/min of hyperbaric aqueous oxygen (AO = oxygen diluted in saline solution) was administered into the PA for 30 minutes. Pulmonary blood flow was maintained during the entire experiment (3.7 +/- 0.3 L/min). RESULTS: Hypoxic ventilation significantly raised (p < 0.05) the systolic (30 +/- 7 vs 21 +/- 4 mm Hg), diastolic (20 +/- 6 vs 12 +/- 3 mm Hg), and mean (23 +/- 7 vs 15 +/- 3 mm Hg) PA pressure; PA/systemic pressure ratio for systolic (0.37 +/- 0.08 vs 0.25 +/- 0.06) and mean (0.56 +/- 0.19 vs 0.29 +/- 0.11) pressures; and pulmonary vascular resistance (PVR) (5.63 +/- 1.06 vs 3.53 +/- 0.75 U). Aqueous oxygen (AO) infusion significantly reduced (p < 0.05) the values obtained with hypoxic ventilation; systolic (23 +/- 5 vs 30 +/- 7 mm Hg), diastolic (11 +/- 4 vs 20 +/- 6 mm Hg), and mean (14 +/- 3 vs 23 +/- 7 mm Hg) PA pressure; PA/systemic pressure ratio for systolic (0.25 +/- 0.05 vs 0.37 +/- 0.08) and mean pressures (0.29 +/- 0.12 vs 0.56 +/- 0.19); and PVR (3.41 +/- 1.01 vs 5.63 +/- 1.06 U). AO infusion in the pulmonary circulation did not influence the myocardial O2 atrioventricular (AV) difference or the O2 extraction. CONCLUSIONS: Infusion of hyperbaric AO solution into the PA can completely reverse the negative effects of acute hypoxia on the pulmonary circulation without affecting the myocardial metabolism.