LY171883 preserves mesenteric perfusion in porcine endotoxic shock

Stephen M. Cohn, Mitchell P. Fink, Patrick C. Lee, Hailong Wang, Heidie R. Rothschild, Yamo F. Deniz, Tad Baum

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14 Scopus citations

Abstract

Superior mesenteric arterial perfusion ( Q ̇) decreases and gut intramucosal hydrogen ion concentration, [H+], increases in resuscitated normodynamic endotoxic pigs. The present study tested the hypothesis that these adverse phenomena can be prevented by pretreatment with LY171883, a specific leukotriene (LT) D4/E4 receptor antagonist. Pentobarbital-anesthetized pigs (14-18 kg) were instrumented to permit measurement of Q ̇ (ultrasonic flow probe) and [H+] (tonometer). Mesenteric O2 delivery (ḊO2) and consumption (V̇O2) were calculated from the O2 contents of arterial and superior mesenteric venous blood. At t = -20 min, groups (N = 6) of pigs were pretreated with LY171883 (10 mg/kg) or vehicle. At t = 0 min, the pigs were infused over 20 min with lipopolysaccharide (LPS; 150 μg/kg) and resuscitated for 2 hr with saline (1.2 ml/kg min). Irrespective of treatment group, mean arterial pressure and systemic vascular resistance index decreased significantly after infusion of LPS. In general, cardiac index (CI) was well preserved, although in controls at t = 20, 100, and 120 min, CI decreased significantly with respect to the t = 0 min value. Normal mesenteric Q ̇ and ḊO2 were maintained in the LY171883 group, whereas, in controls, these parameters decreased significantly. Mesenteric V̇O2 increased transiently but significantly in controls; this phenomenon was abrograted by the LT receptor antagonist. In controls, intramucosal [H+] increased by almost threefold; this adverse effect was significantly ameliorated by LY171883. These data suggest that decreased mesenteric Q ̇ and increased intramucosal [H+] may be mediated by LT in this porcine endotoxic shock model.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalJournal of Surgical Research
Volume49
Issue number1
DOIs
StatePublished - Jul 1990

ASJC Scopus subject areas

  • Surgery

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    Cohn, S. M., Fink, M. P., Lee, P. C., Wang, H., Rothschild, H. R., Deniz, Y. F., & Baum, T. (1990). LY171883 preserves mesenteric perfusion in porcine endotoxic shock. Journal of Surgical Research, 49(1), 37-44. https://doi.org/10.1016/0022-4804(90)90108-E