BACKGROUND Decreased erythrocyte deformability due to cardiopulmonary bypass (CPB) and/or hypothermia, may result in brain capillary beds that have decreased erythrocyte transit, resulting in a generalized impairment of brain oxygenation during CPB. Because brain capillary plasma flow continues even when erythrocyte flow is absent, the authors' hypothesized augmentation of plasma oxygen content with a non-erythrocyte-associated oxygen transport molecule would increase brain oxygen uptake during hypothermic CPB. METHODS Anesthetized New Zealand white rabbits, maintained on CPB at 27 degrees C, were randomized to one of three groups. In group 1 (n = 13), plasma oxygen content was increased by administration of alpha-alpha diaspirin cross-linked hemoglobin. In this group, pretreatment with 0.5 mg/kg verapamil was necessary to prevent hypertension. In group 2 (n = 13), alpha-alpha diaspirin cross-linked hemoglobin was not administered, but verapamil was given as before (control). In group 3 (n = 13), neither alpha-alpha diaspirin cross-linked hemoglobin nor verapamil was administered (control). At 60 min of CPB, cerebral blood flow (microspheres) and cerebral metabolic rate for oxygen (Fick) were determined. RESULTS Systemic physiologic variables did not differ among groups. Although total arterial oxygen content was equivalent in all groups (approximately 12.1 ml O2/dl), the alpha-alpha diaspirin cross-linked hemoglobin group had a much greater proportion of the total arterial oxygen content present in a non-erythrocyte-associated form, 29 +/- 5% versus 6 +/- 2% and 5 +/- 3%, in groups 2 and 3, respectively. Nevertheless, neither cerebral blood flow (approximately 34 ml.100g-1.min-1) nor cerebral metabolic rate for oxygen (approximately 1.2 ml O2.100g-1.min-1) differed among groups. CONCLUSIONS Because oxygen was equally available to the brain in all groups, independent of whether oxygen was associated with erythrocytes or not, it was concluded that erythrocyte/capillary interactions do not limit oxygen transfer from blood to brain during moderately hypothermic CPB. The hypertensive response to alpha-alpha diaspirin cross-linked hemoglobin during CPB is probably a result of nitric oxide scavenging.