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. Relative localization of 99mTc-labeled red blood cells (RBC) in the splanchnic or lung region was not significantly altered by
endotoxin (n = 7) or LY pretreatment (n = 6) compared to vehicle controls (n = 6). In additional studies, small intestinal
luminal content of
99mTc-HSA and 111Indium (In)-labeled RBC were determined after i.v. administration of the
isotopes, in a 4 cm segment of the upper small bowel. Radioactivity in the
luminal lavage was normalized to activity in blood of the same animal.
Endotoxin at 2 hr induced a 2.3-fold increase transluminal leakage of
99mTc-HSA (n = 5; P less than 0.03) compared to LY Veh (n = 5) or control (n = 5) rats.(ABSTRACT TRUNCATED AT 400 WORDS)