BILIRUBIN ENTRY INTO AND CLEARANCE FROM RAT-BRAIN DURING HYPERCARBIA AND HYPEROSMOLALITY

Brain bilirubin concentrations are increased by hyperosmolality and hy percarbia, but the mechanism is not known. The same applies to the mec hanism for preferential localization of bilirubin to basal ganglia. Yo ung Sprague-Dawley rats were used. Groups were: control (n = 15), hype rcarbia (n = 16, pH approximate to 6.95), and hyperosmolality (n = 13, serum osmolality approximate to 390 mosm/L). Hyperbilirubinemia was i nduced by a 5-min infusion of 50 mg/kg bilrubin, containing approximat e to 20 mu Ci [H-3]bilirubin. Rats were killed at 15-min intervals up to 60 min, and the brains were flushed in situ, dissected into seven r egions, weighed, and dissolved. Brain bilirubin was determined by scin tillation counting. The half-life of bilirubin in brain was calculated by exponential fitting, which also allowed an estimation of brain bil irubin at the end of the bilirubin bolus. The kinetics of bilirubin cl earance from brain were first order. The half-life of bilirubin in bra in was significantly prolonged in hyperosmolality (38.2 +/- 28.8 min [ mean +/- SD]) compared with control (16.1 +/- 7.7 min) and hypercarbia (11.6 +/- 8.6 min) (F = 12.6, p < 0.0001 after log transformation) re sults, The estimated acute entry of bilirubin into brain was significa ntly increased in hypercarbia (13.9 +/- 7.4 nmol/g) compared with cont rol(5.6 +/- 3.1 nmol/g) and hyperosmolality (6.5 +/- 2.1 nmol/g) (F = 19.2, p < 0.0001 after log transformation) results. There were no sign ificant differences between brain regions in acute entry or clearance of bilirubin. The kinetics of increased brain bilirubin differ between hypercarbia (increased acute entry) and hyperosmolality (delayed clea rance). Preferential localization of bilirubin to basal ganglia is not produced under, and may not be explained by, the conditions investiga ted.