EFFECTS OF ARTERIAL HYPOXIA AND BETA-ADRENOCEPTOR BLOCKADE ON CEREBRAL BLOOD-FLOW AND OXYGEN-UPTAKE FOLLOWING ESCHERICHIA-COLI ENDOTOXIN INDOGS

Earlier studies in normoxia have shown that an endotoxin injection in dogs leads to an increase in cerebral metabolic rate of oxygen (CMRo(2 )), a decrease in cerebral blood flow (CBF) and increased concentratio ns of monoamines in blood and cerebrospinal fluid (CSF). In animals pr etreated with propranolol (PPL) the CMRo(2) increase was abolished and thus P-adrenoceptor mediated. Arterial hypoxia normally increases CBF without any influence on CMRo(2). The aim of this study was to invest igate the effects of moderate arterial hypoxia on CBF, CMRo(2) and cat echolamine concentrations in blood and CSF after endotoxin with and wi thout pretreatment with PPL. Three groups of dogs were studied. Group 1: Six animals were subjected to arterial hypoxia without any other in tervention. Group 2: Six animals were given an endotoxin injection (E. coli lipopolysaccharide O 111:B 4), before the induction of hypoxia. Group 3: Eight animals were pretreated with PPL per os, 12.5 mg . kg(- 1) twice a day for one week before the experiments, and the effects of arterial hypoxia were studied both before and after an intravenous in jection of endotoxin. Two levels of hypoxia were studied; oxygen satur ation in arterial blood aiming at 75 and 50%. Endotoxin was given intr avenously in a dose of 1 mg . kg(-1) bodyweight over a 5 minute period . After an endotoxin injection, the response to arterial hypoxia was a n increase in CMRo(2), in contrast to the unchanged CMRo(2) without en dotoxin. After pretreatment with PPL the increase in CMRo(2) after end otoxin was prevented. The CBF reaction to hypoxia was uniformly an inc rease. Adrenaline and noradrenaline in blood and noradrenaline in CSF were high and similar in the different hypoxic situations. Indications of a disturbed blood-brain barrier function were found in uptake-rele ase of catecholamines. In conclusion an increase in CMRo(2) and CBF wa s found in moderate arterial hypoxia after an endotoxin injection in d ogs. The increase in CMRo(2) during hypoxia was abolished when the dog s were pretreated with PPL suggesting that it is beta-adrenoceptor med iated.