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: S M Cohn, M P Fink, P C Lee, H Wang, H R Rothschild, Y F Deniz, T Baum
• Journal: The Journal of surgical research (J Surg Res) Vol. 49 Issue 1 Pg. 37-44 (Jul 1990) ISSN: 0022-4804 [Print] United States
• PMID: 1972768 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Acetophenones
• Autacoids
• Azoles
• Tetrazoles
• LY 171883

Topics

• Acetophenones (pharmacology)
• Animals
• Autacoids (antagonists & inhibitors)
• Azoles (pharmacology)
• Escherichia coli
• Hydrogen-Ion Concentration
• Oxygen Consumption (drug effects)
• Shock, Septic (metabolism)
• Splanchnic Circulation (drug effects)
• Swine
• Tetrazoles (pharmacology)