title: Platelet-activating factor mediates pulmonary macromolecular leak following intestinal ischemia-reperfusion.
abstract: Platelet-activating factor (PAF) causes hypotension, cardiac dysfunction, increased vascular permeability, intestinal necrosis, and pulmonary microvascular injury when administered experimentally. Receptor antagonism attenuates or abolishes many of these effects in animal models of bacteremia, endotoxemia, and intestinal ischemia/reperfusion (I/R). The purpose of this study was to further examine the role of PAF in intestinal I/R-induced pulmonary injury using the PAF receptor antagonist WEB 2086. Sprague-Dawley rats were anesthetized and cannulated for measurement of mean arterial pressure, heart rate, and cardiac output. Laparotomy and thoracotomy were performed and the superior mesenteric artery was occluded for 45 min and reperfused for 120 min. Sham animals were treated similarly but without I/R. In the treatment groups, iv WEB 2086 (20 mg/kg/l cc NS) was administered as a bolus 15 min prior to reperfusion. Hemodynamic and videomicroscopic data were obtained before and during ischemia, and after reperfusion at 30-min intervals. Alveolar leak index was calculated offline via computer analysis of videomicroscopic images. Intestinal I/R caused pulmonary macromolecular leakage and hemodynamic instability. Treatment with WEB 2086 attenuated the pulmonary leak during the entire reperfusion period but improved cardiac output only during the first 30 min of reperfusion and had no effect on other hemodynamic variables. These data suggest that PAF is an important, but not the exclusive, mediator of pulmonary injury after intestinal I/R. PAF appears to play a minor role in the hemodynamic derangements observed after rat intestinal I/R.
authors.affiliation: Department of Surgery, University of Louisville, Kentucky 40292, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Carter
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
authors.forename: W B
authors.initials: WB
authors.lastname: Wead
authors.forename: R N
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002199:Capillary Permeability; D006439:Hemodynamics; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086