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This study was designed to explore the mechanisms of previously shown enhanced bilirubin brain deposition in urea induced HO. 28 2-4 day old P were infused with bilirubin(B)to raise & maintain serum B(SB) to approximately 8mg/dl. 14 P served as isoosmotic controls(C),7 P received urea infusions to raise serum osmolality to 330mOsm//L(HO330)& 7 P to 375mOsm/L(HO375). During 60 min of HO, SB was similar among the 3 groups(7-9mg/dl). Serum unbound B(UB) was also similar between HO330&C. In contrast, UB was 2.7-fold higher in HO375 vs C(p<0.01). Microsphere measured regional brain blood flow(RBBF)was similar in cerebrum(CE), thalamus(TH),midbrain(MB),cerebellum(CB),& brainstem(BS)among the 3 groups. RBBD & brain albumin content(BA, 125-I-albumin) are:We conclude that marked HO(375mOsm/L) resulted in enhanced RBBD probably due to HO-related increase in UB & opening of the blood-brain barrier(BBB) to B. Furthermore, opening of the BBB to B may be more pronounced in the CE than in the other regions studied.

Asphyxia (A) and hypotension (H) may alter BBBP and cause cytotoxic edema in piglets (P). 2-4 day old spontaneously breathing P underwent A for 1 hour by exposure to 15% CO2, 12% O2and balanced nitrogen resulting in pH=6.6±0.2, PaO2=34±3mmHg and PaCO2=70±6mmHg, M±SD. During the last 20 min of A, superimposed hemorragic H by phlebotomy (blood removed=30±9 ml/kg), resulted in a fall in mean arterial blood pressure to 29±10 mmHg. BBBP to 24Na and 14C- mannitol was measured as the permeability X surface area product (PS). BBBP, brain water and brain electrolytes were determined 10 min (acute A&H) or 24 hours (post A&H) after A&H. Compared to age matched controls, A&H resulted in the following changes:M±SD, *p<0.05 compared to age matched C, ND:not determined Brain water & electrolytes were similar in all groups. PS for 24Na and M was decreased following acute A&H. Na/M values were similar in acute A & H vs C indicating a lack of change in the endothelial "pore" size. The decrease in PS may indicate a reduction in Na and M transport and/or more likely a reduction in brain endothelial capillary surface area.

Effects of fetal hyperinsulinemia were examined in six chronically catheterized ovine fetus (F), receiving 0.2 U/kg/hr of insulin (I) continuously for 24 hours, followed by 0.4 U/kg/hr of I for an additional 24 hours. Hemodynamic changes (microsphere method), fetal arterial levels of I, glucose (G), norepinephrine (NE) and O2content were determined at 2 and 24 hours of each infusion period. Data (M±SD) are shown below:Fetal hyperinsulinemia resulted in increased fetal O2consumption (FVO2) which in turn produced a surge in catecholamine (NE) release. The latter mediated an increase in CO, with a redistribution of CO providing a greater proportion distributed to the fetus at the expense of the placenta. We speculate that hemodynamic adjustments with a decrease in placental blood flow may occur in pregnancies complicated by fetal hyperinsulinemia.

Hypercarbia (HC) induced increases in regional brain blood flow (RBBF) may augment regional brain bilirubin deposition (RBBD) in piglets (P). 10 2-4 day old P were infused with bilirubin (BR) to raise & maintain a serum BR of approximately 8 mg/dl. HC (pCO2=76mmHg) was induced with 15% CO2. 14 control (C) P had similar BR levels without HC. Serum free bilirubin was similar in C & HC P. RBBF (by microspheres) & RBBD were as follows:(M±SEM) *p<0.05 vs C, +p<0.05 vs CE value within HC group, CE-cerebrum,TH-thalamus,MB-midbrain,CB-cerebellum,BS-brainstemRBBF was elevated in all regions during HC; the increases in the TH, MB & BS, were greater than for the CE. RBBD was increased following HC in MB & CB; and the increases in MB, CB, & BS were higher than for CE. Regional brain albumin deposition (125I-albumin) was similar in all brain regions. We conclude that deposition of unbound bilirubin in some brain regions is blood flow dependent.