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Title: Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock

Abstract

Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock. In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat. Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.). Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization. Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle. In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5). Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold)more » by endotoxin compared to vehicle controls. Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin. LY reduced the mesenteric permeability index by 70%. Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment. Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds.« less

Authors:
; ; ; ;  [1]
  1. Medical Univ. of South Carolina, Charleston (USA)
Publication Date:
OSTI Identifier:
6247950
Resource Type:
Journal Article
Journal Name:
Circulatory Shock; (USA)
Additional Journal Information:
Journal Volume: 32:3; Journal ID: ISSN 0092-6213
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; BACTERIAL DISEASES; PATHOGENESIS; BLOOD VESSELS; PERMEABILITY; PEPTIDES; BIOLOGICAL FUNCTIONS; ABDOMEN; ALBUMINS; GAMMA CAMERAS; HEART; IMAGE PROCESSING; ISOMERIC NUCLEI; LUNGS; PROSTAGLANDINS; RATS; RECEPTORS; SALMONELLA; TECHNETIUM 99; ANIMALS; BACTERIA; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BODY; BODY AREAS; CAMERAS; CARDIOVASCULAR SYSTEM; DISEASES; FUNCTIONS; HOURS LIVING RADIOISOTOPES; INFECTIOUS DISEASES; INTERMEDIATE MASS NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; MAMMALS; MEMBRANE PROTEINS; MICROORGANISMS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; PROCESSING; PROTEINS; RADIOISOTOPES; RESPIRATORY SYSTEM; RODENTS; TECHNETIUM ISOTOPES; VERTEBRATES; YEARS LIVING RADIOISOTOPES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics; 550901 - Pathology- Tracer Techniques

Citation Formats

Cook, J A, Li, E J, Spicer, K M, Wise, W C, and Halushka, P V. Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock. United States: N. p., 1990. Web.
Cook, J A, Li, E J, Spicer, K M, Wise, W C, & Halushka, P V. Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock. United States.
Cook, J A, Li, E J, Spicer, K M, Wise, W C, and Halushka, P V. 1990. "Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock". United States.
@article{osti_6247950,
title = {Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock},
author = {Cook, J A and Li, E J and Spicer, K M and Wise, W C and Halushka, P V},
abstractNote = {Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock. In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat. Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.). Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization. Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle. In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5). Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold) by endotoxin compared to vehicle controls. Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin. LY reduced the mesenteric permeability index by 70%. Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment. Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds.},
doi = {},
url = {https://www.osti.gov/biblio/6247950}, journal = {Circulatory Shock; (USA)},
issn = {0092-6213},
number = ,
volume = 32:3,
place = {United States},
year = {Thu Nov 01 00:00:00 EST 1990},
month = {Thu Nov 01 00:00:00 EST 1990}
}