Hemolytic anemia does not increase entry into, nor alter rate of clearance of bilirubin from rat brain.

Abstract

The risk of bilirubin encephalopathy is believed to be increased in hemolytic relative to nonhemolytic jaundice. Young SPRD rats were injected with either acetylphenylhydrazine (APHZ, n = 22) 75 mg/kg or an equivalent volume of the solvent (control, n = 22) intraperitoneally for 3 successive days. One the 4th day, hyperbilirubinemia was induced by a 5-min intravenous infusion of 50 mg/kg bilirubin. After sacrifice (at 10 or 60 min) the brain vessels were flushed in situ with ice-cold saline. Serum bilirubin was 600 +/- 108 mumol/l (mean +/- SD) at 10 min, and 295 +/- 98 mumol/l at 60 min. Hematocrit was significantly reduced in the APHZ rats versus controls (26 +/- 3 vs. 41 +/- 3, p < 0.0001). The concentration of bilirubin in brain was determined by acid chloroform extraction and diazotization. The brain bilirubin values were 5.5 +/- 1.5 versus 5.4 +/- 2.1 mmol/g at 10 min (APHZ vs. control), and 1.3 +/- 0.6 versus 0.8 +/- 0.7 nmol/g at 60 min. The half-life of bilirubin in brain was calculated with an exponential fitting program. The half-life of bilirubin in brain for the two groups was 24.3 +/- 21.9 versus 18.5 +/- 28.3 min. There were no significant differences between the groups in either of these measures. We conclude that in young rats, hemolytic anemia does not increase the acute entry of bilirubin into brain, nor does it affect the clearance of bilirubin from brain.