THE ROLE OF HISTAMINE IN MEDIATING THE DECOMPENSATORY PHASE OF HEMORRHAGIC-SHOCK IN THE RAT

Our laboratory has previously reported that plasma histamine levels ri se significantly and coincidentally with the onset oi the decompensato ry phase of isobaric hemorrhagic shock in rats. The histamine levels s een in shock were comparable to those that induce profound vasodilatat ion in many vascular beds under normovolemic conditions. We, therefore , sought to determine whether the elevation in plasma histamine contri butes to the cardiovascular collapse seen in the decompensatory phase of hemorrhagic shock. Sprague-Dawley rats were bled according to an is obaric bleeding protocol which maintained the mean arterial blood pres sure (MAP) at 40 mmHg until death. Selected H-1 (diphenhydramine) and/ or H-2 (cimetidine and famotidine) antagonists were administered at 75 % of the estimated peak shed blood volume (PSBV), a point preceding th e 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 histami ne administration on MAP before and after hemorrhage. In unbled animal s, bolus histamine in 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 the se two interventions, we conclude that histamine is not an important m ediator of the cardiovascular collapse seen in the decompensatory phas e of hemorrhagic shock in the rat.