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

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 concentrations of monoamines in blood and cerebrospinal fluid (CSF). In animals pretreated 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 investigate the effects of moderate arterial hypoxia on CBF, CMRo(2) and catecholamine concentrations in blood and CSF after endotoxin with and without pretreatment with PPL. Three groups of dogs were studied. Group 1: Six animals were subjected to arterial hypoxia without any other intervention. 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 injection of endotoxin. Two levels of hypoxia were studied; oxygen saturation in arterial blood aiming at 75 and 50%. Endotoxin was given intravenously in a dose of 1 mg . kg(-1) bodyweight over a 5 minute period. After an endotoxin injection, the response to arterial hypoxia was an increase in CMRo(2), in contrast to the unchanged CMRo(2) without endotoxin. After pretreatment with PPL the increase in CMRo(2) after endotoxin was prevented. The CBF reaction to hypoxia was uniformly an increase. 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-release of catecholamines. In conclusion an increase in CMRo(2) and CBF was found in moderate arterial hypoxia after an endotoxin injection in dogs. The increase in CMRo(2) during hypoxia was abolished when the dogs were pretreated with PPL suggesting that it is beta-adrenoceptor mediated.