Effects of propranolol pretreatment on cerebral blood flow, oxygen uptake and catecholamines during metabolic acidosis following E. coli endotoxin in dogs.
After an intravenous injection of E. coli endotoxin in dogs a decrease in cerebral blood flow (CBF) and an increase in cerebral metabolic rate of oxygen (CMRo2) have been shown to occur. In metabolic acidosis following endotoxin CMRo2 increased with decreasing pH. A possible explanation for the increased CMRo2 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 CMRo2 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 CMRo2 or CBF was observed with increasing acidosis in the PPL-group. In the control group, after endotoxin, both CBF and CMRo2 increased with decreasing pH. This resulted in a significant difference in both CBF and CMRo2 between the groups in the pH range 7.01-7.15. The present results indicate that the increase in CMRo2 and CBF with metabolic acidodis in endotoxinaemia is mediated via beta-adrenoceptors.
Westerlind
A
A
Department of Anaesthesiology, Sahlgren's Hospital, University of Göteborg, Sweden.
Larsson
L E
LE
Häggendal
J
J
Ekström-Jodal
B
B
D000138:Acidosis / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004285:Dogs; D004731:Endotoxins / Q000009:adverse effects* / Q000097:blood; D004837:Epinephrine / Q000097:blood / Q000134:cerebrospinal fluid; D004926:Escherichia coli; D006851:Hydrochloric Acid / Q000009:adverse effects; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000009:adverse effects*; D009638:Norepinephrine / Q000097:blood / Q000134:cerebrospinal fluid; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D002395:Catecholamines; D004731:Endotoxins; D008070:Lipopolysaccharides; D011943:Receptors, Adrenergic, beta; C044101:endotoxin, Escherichia coli; D011433:Propranolol; D006851:Hydrochloric Acid; D010100:Oxygen; D009638:Norepinephrine; D004837:Epinephrine