Background.The purpose of this study was to determine the impact of perfusion pressure on cerebral blood flow (CBF) and metabolism during normothermic cardiopulmonary bypass (CPB) and after weaning.Materials and methods.Two groups of mongrel dogs were studied (Group A, CPB perfusion at 50 mm Hg,n= 6; and Group B, CPB perfusion at 100 mm Hg,n= 6). All animals underwent 2 h of normothermic bypass at cardiac indexes >2.1 L/min/m2and were weaned from pump, maintained at pressures >75 mm Hg, and followed for an additional 2 h.Results.In both groups CBF increased over 85% from baseline, in proportion to the hemodilution during the initiation of CPB. Intracranial pressure increased moderately in both groups during CPB, compromising CBF at 1 h in Group A, but not in Group B. The Group A cerebral metabolic rate for oxygen (CMRO2), however, remained unchanged as the percentage of oxygen extraction increased to compensate for the decreased CBF. During recovery, temperature, mean arterial pressure, and cerebral perfusion pressure were not significantly different between the two groups. However, the CBF, percentage of oxygen extracted, and CMRO2were significantly lower in Group A.Conclusions.Normothermic CPB initiated with a crystalloid prime and performed at the lower end of a 50–70 mm Hg perfusion window resulted in a highly significant increase in CBF in order to compensate for hemodilution, while at the same time reduced the perfusion pressure available to supply the increased CBF. Together, these two events create a hemodynamic paradox of hyperperfusion in the face of hypotension. The reduction in CMRO2in Group A is yet to be explained but seems to remain coupled to CBF and could represent a previously undescribed protective mechanism of hibernating cerebral tissue, similar to the phenomena of ischemic preconditioning in the heart, where cerebral tissue is stimulated to lower metabolism in response to inadequate CBF.