title: The role of histamine in mediating the decompensatory phase of hemorrhagic shock in the rat.
abstract: Our laboratory has previously reported that plasma histamine levels rise significantly and coincidentally with the onset of the decompensatory phase of isobaric hemorrhagic shock in rats. The histamine levels seen in shock were comparable to those that induce profound vasodilatation in many vascular beds under normovolemic conditions. We, therefore, sought to determine whether the elevation in plasma histamine contributes to the cardiovascular collapse seen in the decompensatory phase of hemorrhagic shock. Sprague-Dawley rats were bled according to an isobaric bleeding protocol which maintained the mean arterial blood pressure (MAP) at 40 mmHg until death. Selected H1 (diphenhydramine) and/or H2 (cimetidine and famotidine) antagonists were administered at 75% of the estimated peak shed blood volume (PSBV), a point preceding the rise in plasma histamine. Plasma histamine levels in all groups were similar throughout the time course of hemorrhagic shock. None of the histamine receptor antagonists affected the time of onset or the rate of decompensation. Suspecting that hypotension may alter the animal's response to histamine, we investigated the effect of exogenous histamine administration on MAP before and after hemorrhage. In unbled animals, bolus histamine infusions (.6 mg/kg) dropped the MAP by 62.0 +/- 2.7 mmHg, however, in animals bled to 40 mmHg, histamine dropped the MAP by 7.2 +/- 2.7 mmHg (p = .002). On the basis of the results of these two interventions, we conclude that histamine is not an important mediator of the cardiovascular collapse seen in the decompensatory phase of hemorrhagic shock in the rat.
authors.affiliation: Division of Surgery, Walter Reed Army Institute of Research, Washington DC 20307-5100, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Johnson
authors.forename: R V
authors.initials: RV
authors.lastname: Charya
authors.forename: J L
authors.initials: JL
authors.lastname: Atkins
authors.forename: W P
authors.initials: WP
authors.lastname: Wiesmann
authors.forename: F J
authors.initials: FJ
authors.lastname: Pearce
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D006633:Histamine Antagonists; D011968:Receptors, Histamine; D006632:Histamine