title: Naloxone does not inhibit the attenuation of the response to severe haemorrhage seen after simulated injury in the anaesthetized rat.
abstract: Severe haemorrhage leads to a reflex bradycardia and hypotension. This is thought to be protective, but is attenuated by both concomitant musculoskeletal injury and exogenous morphine. The aim of this study was to determine whether the injury-induced attenuation of the response to severe haemorrhage could be blocked by naloxone. Male Wistar rats, terminally anaesthetized with alphadolone/alphaxalone (19-20 mg kg(-1) h(-1)I.V.), were randomly allocated to one of four groups. In groups I and IV, haemorrhage was simple [40% of estimated total blood volume (BV)], while in groups II and III it was initiated 10 min after the onset of bilateral hindlimb ischaemia (a model of musculoskeletal injury). Groups I and II received 20 microl of 0.9% saline intracerebroventricularly (I.C.V.) immediately before haemorrhage, while groups III and IV received 20 microg of naloxone I.C.V., in the same volume. In group I, the bradycardia reached its peak after the loss of 32.8 +/- 0.3% BV (mean +/- S.E.M.). Blood pressure did not fall significantly until the loss of 15.0 +/- 3.0% BV. The response in group IV was not significantly different from group I. By contrast, the bradycardia was absent after similar blood losses in groups II and III, while hypotension was attenuated. These results indicate that naloxone, at a dose known to be effective in blocking mu-opioid receptors and preventing other aspects of the response to injury, does not prevent the injury-induced attenuation of the response to severe haemorrhage. Thus the attenuation of the response to blood loss by injury is unlikely to be mediated via the mu-opioid receptors.
authors.affiliation: School of Medicine and Health, Durham University, Stockton-on-Tees, UK. marina.sawdon@durham.ac.uk
authors.forename: Marina
authors.initials: M
authors.lastname: Sawdon
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Little
authors.forename: Emrys
authors.initials: E
authors.lastname: Kirkman
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001810:Blood Volume / Q000502:physiology; D001919:Bradycardia / Q000209:etiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006470:Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D006614:Hindlimb; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D009141:Musculoskeletal System / Q000293:injuries / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone