An analysis of hypoxia in sheep brain using a mathematical model

Cerebral blood flow (CBF) increases as arterial oxygen content falls with hypoxic (low PO2), anemic (low hemoglobin) and carbon monoxide (CO) (high carboxyhemoglobin) hypoxia. Despite a higher arterial PO2, CO hypoxia provokes a greater increase in CBF than hypoxic hypoxia. We analyzed published data using a compartmental mathematical model to test the hypothesis that differences in PO2 in tissue, or a closely related vascular compartment, account for the greater response to CO hypoxia. Calculations showed that tissue, but not arteriolar, PO2 was lower in CO hypoxia because of the increased oxyhemoglobin affinity with CO hypoxia. Analysis of studies in which oxyhemoglobin affinity was changed independently of CO supports the conclusion that changes in tissue PO2 (or closely related capillary or venular PO2) are predictive of alterations in CBF. We then sought to determine the role of tissue PO2 in anemic hypoxia, with no change in arterial and little, if any, change in venous PO2. Calculations predict a small fall in tissue PO2 as hematocrit decreases from 55% to 20%. However, calculations show that changes in blood viscosity can account for the increase in CBF in anemic hypoxia over this range of hematocrits.