title: LY171883 preserves mesenteric perfusion in porcine endotoxic shock.
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 (DO2) and consumption (VO2) 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 micrograms/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 DO2 were maintained in the LY171883 group, whereas, in controls, these parameters decreased significantly. Mesenteric VO2 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.
authors.affiliation: University of Massachusetts Medical Center, Worcester 01655.
authors.forename: S M
authors.initials: SM
authors.lastname: Cohn
authors.forename: M P
authors.initials: MP
authors.lastname: Fink
authors.forename: P C
authors.initials: PC
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: H R
authors.initials: HR
authors.lastname: Rothschild
authors.forename: Y F
authors.initials: YF
authors.lastname: Deniz
authors.forename: T
authors.initials: T
authors.lastname: Baum
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D012898:Autacoids / Q000037:antagonists & inhibitors*; D001393:Azoles / Q000494:pharmacology*; D004926:Escherichia coli; D006863:Hydrogen-Ion Concentration; D010101:Oxygen Consumption / Q000187:drug effects; D012772:Shock, Septic / Q000378:metabolism*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000098:Acetophenones; D012898:Autacoids; D001393:Azoles; D013777:Tetrazoles; C044660:LY 171883