CONCENTRATION AND FLOW RELATIONSHIPS FOR ENTRY OF UNBOUND BILIRUBIN (BR) IN RAT BRAIN

Abstract

To estimate the influence of concentration (C), time (t) and rate of flow (F) on unbound bilirubin (BR) uptake across the blood-brain barrier, we injected unbound BR into the carotid artery in 22 adult rats. BR concentrations were between 1 and 10mg%; injection rates were 4.4, 6.0, 8.6, and 12 ml/min.; and injection times were from 10-60 sec. Permeability of BR and capillary surface area were assumed constant. After saline perfusion of the carotid arteries, brain BR was measured by chloroform extraction and diazotization. At t≥20 sec, arterial unbound BR concentrations (C) ≥1mg% produced visible staining of the injected hemisphere. Values of (C × t) uncorrected for flow, were correlated with brain BR:r = 0.540, r2 = 0.29, p<0.01. Correction of (C × t) for relative flow changes (F) as determined by changes in injection rate improved the correlation of (C × t × F) with brain BR to r = 0.834, r2 = 0.70, p<0.001. (C × t) accounted for 29% of the variance in brain BR independent of flow, while correction of (C × t) for different injection rates (C × t × F) accounted for 70% of the variance in brain BR. We conclude that whole brain uptake of injected unbound BR in adult rats is related to carotid artery injection rate as well as to arterial concentration of unbound BR and time of exposure. These findings are consistent with rapid entry of unbound BR into the brain when blood flow and the blood-brain barrier are normal, and with the hypothesis that increased brain blood flow may increase brain deposition of BR.