Cerebral blood flow (CBF), cerebral oxygen uptake (CMRO2) and central haemodynamics in anaesthetized dogs with controlled ventilation were studied at intervals for 2 h following an intravenous injection of E. coli endotoxin, 1.0-1.5 mg/kg. CBF showed a 30% decrease within 15 min after the endotoxin administration, while the arterial blood pressure was still not markedly depressed. Autoregulation to arterial blood pressure changes was maintained during endotoxinaemia and the cerebrovascular reaction to changes in arterial carbon dioxide tension (PaCO2) depressed. Normocapnic animals (PaCO2) greater than or equal to 4.0 kPa) showed an increase in CMRO2 of over 40%, that was obvious 1 h after the administration of endotoxin. The intracranial pressure was decreased with 5 min of the administration of endotoxin irrespective of the prevailing arterial blood pressure. Thereafter, it was raised above the control level. Two hours after endotoxin increased protein concentrations in cerebrospinal fluid were seen, results compatible with blood-brain barrier damage and penetration of other substances; e.g. monoamines released during endotoxinaemia could thus be expected to have a direct influence on both cerebral blood flow and metabolism.

In an earlier study in dogs we found a reduced cerebral blood flow measured intermittently during the first hours after an intravenous injection of E. coli endotoxin. Within 5 min after the endotoxin injection, a temporarily reduced cerebrospinal fluid pressure was seen irrespective of changes in arterial blood pressure. One possible explanation for this could be an early reduction of the blood flow in the brain. To test this hypothesis, the initial flow reaction was evaluated by measurement of the blood flow in the superior sagittal sinus using an electromagnetic probe around the intact sinus. In five animals following E. coli endotoxin 1.0-1.5 mg/kg intravenously, the superior sagittal sinus blood flow decreased within 2 min, followed by increasing flows within 15 min and thereafter continuously decreasing values up to 60 min, thus giving a two-phase vascular reaction. In all animals there was a marked initial increase in cerebrovascular resistance and the fall in blood flow was thus not a mere consequence of blood pressure changes. In three other animals pretreated with methysergide, a serotonin antagonist, no increase in cerebrovascular resistance was seen during the initial phase. Later, the reaction was similar in all eight animals.