title: Adrenal vein and arterial levels of catecholamines and immunoreactive metenkephalin in canine endotoxin shock and their response to naloxone.
abstract: The alterations in plasma levels of immunoreactive metenkephalin (ir-metenkephalin) and catecholamines in adrenal vein and arterial blood in response to endotoxin, as well as the effects of subsequent naloxone administration, have been investigated in a canine model. Animals were anaesthetised with alpha chloralose and allowed to breathe spontaneously. The left lumbar adrenal vein was cannulated and an intermittent choke allowed retrograde sampling of the adrenal effluent. Severe shock was produced by the administration of a large bolus of E. coli endotoxin (5 mg/kg) followed by a continuous infusion (2 mg/kg per hour). One hour after induction of shock the circulating volume was expanded using a colloidal gelatin solution. Thirty minutes later one group of five animals received a bolus of naloxone (2 mg/kg) followed by a continuous infusion of (1.5 mg/kg per hour), while a control group of five animals was given an equivalent volume of isotonic saline. The production of endotoxin shock was associated with marked increases in adrenal vein and systemic levels of adrenaline and noradrenaline. Naloxone administration transiently limited the fall in adrenal vein levels of adrenaline and noradrenaline (P less than 0.05) following volume replacement and was associated with a sustained increase in systemic adrenaline levels (P less than 0.05). Changes in mean arterial pressure confirmed a significant haemodynamic response to naloxone (P less than 0.05). Alterations in ir-metenkephalin levels in the adrenal vein closely followed the changes in catecholamines, whereas arterial levels rose progressively and were unaffected by naloxone. We conclude that in canine endotoxin shock the opiate antagonist naloxone can transiently increase catecholamine levels in the adrenal effluent and produce a more sustained rise in systemic adrenaline levels. Moreover, the adrenal medulla is not the only source of circulating ir-metenkephalin.
authors.affiliation: Anaesthetics Laboratory, St. Bartholomew's Hospital, London, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Watson
authors.forename: J G
authors.initials: JG
authors.lastname: Varley
authors.forename: P M
authors.initials: PM
authors.lastname: Bouloux
authors.forename: S J
authors.initials: SJ
authors.lastname: Tomlin
authors.forename: L H
authors.initials: LH
authors.lastname: Rees
authors.forename: G M
authors.initials: GM
authors.lastname: Besser
authors.forename: C J
authors.initials: CJ
authors.lastname: Hinds
mesh_terms: D000311:Adrenal Glands / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001158:Arteries; D004195:Disease Models, Animal; D004285:Dogs; D004731:Endotoxins; D004744:Enkephalin, Methionine / Q000097:blood / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D012016:Reference Values; D012772:Shock, Septic / Q000503:physiopathology*; D014680:Veins
chemical_list: D004731:Endotoxins; D009270:Naloxone; D004744:Enkephalin, Methionine; D009638:Norepinephrine; D004837:Epinephrine