EFFECTS OF PROPRANOLOL PRETREATMENT ON CEREBRAL BLOOD-FLOW, OXYGEN-UPTAKE AND CATECHOLAMINES DURING METABOLIC-ACIDOSIS FOLLOWING ESCHERICHIA-COLI ENDOTOXIN IN DOGS

After an intravenous injection off. rob endotoxin in dogs a decrease in cerebral blood how (CBF) and an increase in cerebral metabolic rate of oxygen (CMRo(2)) have been shown to occur. In metabolic acidosis following endotoxin CMRo(2) increased with decreasing pH. A possible explanation for the increased CMRo(2) after endotoxin and metabolic acidosis seems to be a damage of the blood-brain barrier (BBB) by endotoxin. This gives possibilities for a leakage of hydrogen ions and circulating monoamines from the blood to the brain, thus affecting the cerebral blood flow and metabolism. The effects of an E. coli endotoxin injection on CBF and CMRo(2) during metabolic acidosis and beta-adrenoceptor blockade were studied in eight anaesthetized dogs. All the dogs were pretreated with propranolol (PPL), per os 12.5 mg . kg(-1) twice a day for one week. Metabolic acidosis (pH 7.01-7.30) was achieved by an intravenous infusion of hydrochloric acid. Endotoxin E. coli lipopolysaccharide O 111:B 4 was given as an intravenous injection of 1 mg . kg(-1) bodyweight over a 5 min period. Another five animals, published earlier, with the same experimental protocol but without PPL, constituted a control group. After endotoxin no increase in CMRo(2) or CBF was observed with increasing acidosis in the PPL-group. In the control group, after endotoxin, both CBF and CMRo(2) increased with decreasing pH. This resulted in a significant difference in both CBF and CMRo(2) between the groups in the pH range 7.01-7.15. The present results indicate that the increase in CMRo(2) and CBF with metabolic acidodis in endotoxinaemia is mediated via beta-adrenoceptors.