title: Morphine blocks the bradycardia associated with severe hemorrhage in the anesthetized rat.
abstract: Progressive hemorrhage in the absence of tissue injury produces a biphasic response: an initial tachycardia, vasoconstriction and maintenance of arterial blood pressure by the baroreflex, followed by bradycardia, vasodilatation and hypotension due to the activation of a second 'depressor' reflex. The present study has investigated the effect of morphine (a mu-opioid receptor agonist) on the cardiac chronotropic response to a progressive hemorrhage at 2% total estimated blood volume (BV) min(-1) in the anesthetized rat. In control rats (20 microl saline intracerebroventricularly, i.c.v.) heart period initially decreased significantly (P < 0.05) by a maximum of 5.4 +/- 0.8 ms from a baseline of 147.3 +/- 2.2 ms after a blood loss of 8.3 +/- 1.5% BV, and then increased significantly by a maximum of 43.0 +/- 5.5 ms above the baseline after the loss of 34.5 +/- 1.6% BV. Blood pressure was initially maintained and then fell during the hemorrhage. The increase in heart period was prevented by treatment with morphine (10 microg i.c.v.), and the fall in blood pressure delayed significantly. These effects of morphine were prevented by pretreatment with naloxone (20 microg i.c.v.). Intravenous (i.v.) administration of morphine (10 microg) had no effect on the response to hemorrhage. However, a clinically relevant dose of 0.5 mg x kg(-1) morphine (i.v.) abolished the bradycardia and delayed the fall in blood pressure associated with hemorrhage. These results indicate that morphine, acting on central nervous opioid receptors, can abolish the bradycardia and delay the hypotension associated with progressive hemorrhage, a pattern of response reminiscent of the effects of musculo-skeletal injury on the response to blood loss.
authors.affiliation: North Western Injury Research Centre, University of Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ohnishi
authors.forename: E
authors.initials: E
authors.lastname: Kirkman
authors.forename: H W
authors.initials: HW
authors.lastname: Marshall
authors.forename: R A
authors.initials: RA
authors.lastname: Little
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001919:Bradycardia / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology; D007022:Hypotension / Q000188:drug therapy; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009020:Morphine