The events resulting in the hepatic coma which follows this massive hepatic necrosis or hepatectomy have never been adequately defined. This study was directed at the possibility that part of the abnormality might be at the level of the blood-brain barrier. Bloodless two-stage hepatectomies were performed on Wistar rats and the animals were maintained with intravenous glucose infusions. When the animals were in late stage 3 or stage 4 hepatic coma the functional integrity of the blood-brain barrier was assessed by means of the sudden arterial injection-15-sec decapitation-Oldendorf tissue residue technique, and by the intravenous injection of trypan blue. The former showed that the barrier had become permeable to D-sucrose, inulin, and L-glucose, substances which usually do not cross the barrier; the latter showed that the barrier had also become permeable to trypan blue, so that the brains of the comatose animals stained blue whereas normal brains did not. The brains of comatose animals uniformly showed cerebral edema on gross examination (their water contents were increased); and on electron microscopic examination their astrocytes were swollen, especially in pericapillary locations. The break in the barrier appears to be associated with the formation of cerebral edema, and implies both that substances which usually do not gain access to the brain parenchyma can now do so and that substances usually conserved, such as neurotransmitters, can now escape.
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