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Effect of inhaled endotoxin on cardiopulmonary function and E-selectin expression in pigs

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  • 1 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706-1102.
  • | 2 Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706-1102.
  • | 3 Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706-1102.
  • | 4 Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706-1102.

Abstract

Objective—To evaluate the effect of controlled exposure to inhaled lipopolysaccharides (LPS) on the pulmonary inflammatory response of anesthetized pigs.

Animals—Forty-seven 8- to 12-week-old domestic pigs.

Procedure—Pigs were anesthetized with pentobarbital, instrumented for measurement of cardiopulmonary function, and randomly assigned to receive saline (0.9% NaCl) solution or 0.25, 0.5, or 1.0 µg of LPS/kg/h for 2 or 6 hours via nebulization through the endotracheal tube. Cardiopulmonary variables were measured, ex vivo neutrophil superoxide production determined, and postmortem assessment for pulmonary neutrophil influx and modulation of adhesion molecule (E-selectin) expression was done.

Results—Mild changes in cardiopulmonary function were observed in response to inhaled LPS in the 2- and 6-hour groups. In pigs inhaling LPS (0.5 or 1.0 µg/kg/h) for 6 hours, there was significant pulmonary neutrophil influx observed postmortem. An increase in expression of E-selectin on pulmonary endothelial cells after 6 hours of LPS inhalation (0.5 µg/kg/h) was also observed. In contrast, there was no significant influx of neutrophils or expression of E-selectin in lungs from pigs inhaling LPS for 2 hours.

Conclusion and Clinical Relevance—Inhalation of LPS resulted in localized pulmonary inflammation characterized by neutrophil influx and increased expression of the endothelial cell adhesion molecule, E-selectin. It may be possible to relate our experimental findings to the clinical consequences of airborne LPS exposure in swine confinement facilities. (Am J Vet Res 2002;63:1302–1308)

Abstract

Objective—To evaluate the effect of controlled exposure to inhaled lipopolysaccharides (LPS) on the pulmonary inflammatory response of anesthetized pigs.

Animals—Forty-seven 8- to 12-week-old domestic pigs.

Procedure—Pigs were anesthetized with pentobarbital, instrumented for measurement of cardiopulmonary function, and randomly assigned to receive saline (0.9% NaCl) solution or 0.25, 0.5, or 1.0 µg of LPS/kg/h for 2 or 6 hours via nebulization through the endotracheal tube. Cardiopulmonary variables were measured, ex vivo neutrophil superoxide production determined, and postmortem assessment for pulmonary neutrophil influx and modulation of adhesion molecule (E-selectin) expression was done.

Results—Mild changes in cardiopulmonary function were observed in response to inhaled LPS in the 2- and 6-hour groups. In pigs inhaling LPS (0.5 or 1.0 µg/kg/h) for 6 hours, there was significant pulmonary neutrophil influx observed postmortem. An increase in expression of E-selectin on pulmonary endothelial cells after 6 hours of LPS inhalation (0.5 µg/kg/h) was also observed. In contrast, there was no significant influx of neutrophils or expression of E-selectin in lungs from pigs inhaling LPS for 2 hours.

Conclusion and Clinical Relevance—Inhalation of LPS resulted in localized pulmonary inflammation characterized by neutrophil influx and increased expression of the endothelial cell adhesion molecule, E-selectin. It may be possible to relate our experimental findings to the clinical consequences of airborne LPS exposure in swine confinement facilities. (Am J Vet Res 2002;63:1302–1308)