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Kinetics of endotoxin concentration and tumor necrosis factor-α, interleukin-1β, and interleukin-6 activities in the systemic and portal circulation during small intestinal ischemia and reperfusion in dogs
2002
Nezu, Yoshinori | Tagawa, Masahiro | Sakaue, Yoko | Hara, Yasushi | Tsuchida, Shuichi | Ogawa, Ryo
Objective-To determine whether small intestinal ischemia and reperfusion induces bacterial translocation and proinflammatory cytokine response in either the systemic or portal circulation in dogs. Animals-17 healthy adult Beagles. Procedure-The superior mesenteric artery (SMA) was occluded for 0 (group-3 dogs), 30 (group-1 dogs), or 60 (group-2 dogs) minutes, followed by reperfusion for 180 minutes; serum lactate and endotoxin concentrations and tumor necrosis factor-alpha (TNF-alpha), interleukin- 1beta (IL-1beta), and IL-6 activities in the systemic and portal circulation and intramucosal pH were measured at various time points. Results-In group-2 dogs, TNF-alpha activity was found to be significantly increased in the portal circulation, peaking at 60 minutes of reperfusion; TNF-alpha activity, in the systemic circulation, gradually increased from 60 minutes of reperfusion to the end of the experiment; however, the increase was not significant. In group-1 and -2 dogs, IL-6 activities significantly and gradually increased in the systemic and portal circulation during the reperfusion phase, and the magnitude of these increases was dependent on the duration of the ischemic phase. There were no significant changes in IL-1beta activity or endotoxin concentration in any dog group. Conclusions and Clinical Relevance-Results of the our study indicate that intestinal ischemia and reperfusion leads to significant increases of the circulating TNF-alpha and IL-6 activities, depending on the duration of the ischemia phase, in the absence of detectable endotoxin in the circulation. This finding suggests that intestinal ischemia and reperfusion induces a systemic proinflammatory cytokine response in dogs.
Show more [+] Less [-]Effect of administration of a phospholipid emulsion on the initial response of horses administered endotoxin
2002
Winchell, Wyatt W. | Hardy, Joanne | Levine, Daniel M. | Parker, Thomas S. | Gordon, Bruce R. | Saal, Stuart D.
Objective-To evaluate the effect of a phospholipid emulsion (PLE) on the initial response of horses to administration of endotoxin. Animals-12 healthy adult horses. Procedures-Horses were assigned to 2 treatment groups (6 horses/group). The control group was administered 1 L of saline (0.9% NaCl) solution, and the treated group was administered PLE (200 mg/kg, IV); treatments were administered during a period of 120 minutes. An infusion of endotoxin was initiated in both groups starting 1 hour after initiation of the saline or PLE solutions. Physical examination and hemodynamic variables were recorded, and blood samples were analyzed for concentrations of tumor necrosis factor (TNF)-α, interleukin-6, thromboxane B2 (TxB2), 6 keto-prostaglandin F (PGF)1α, total leukocyte count, and PLE concentrations. An ANOVA was used to detect significant differences. Results-Administration of PLE resulted in significantly lower rectal temperature, heart rate, cardiac output, right atrial pressure, and pulmonary artery pressure and higher total leukocyte counts in treated horses, compared with values for control horses. The TNF-α concentration was significantly less in treated horses than in control horses. The TxB2 and 6 keto- PGF1α concentrations were significantly different between treated and control horses at 30 minutes (TxB2) and at 30 and 60 minutes (6 keto-PGF1α). Conclusions and Clinical Relevance-Prior infusion of PLE in horses administered a low dose of endotoxin decreased rectal temperature, heart rate, pulmonary artery pressure, and TNF-α concentrations. Results of this study support further evaluation of PLE for use in the treatment of horses with endotoxemia.
Show more [+] Less [-]Effect of inhaled endotoxin on cardiopulmonary function and E-selectin expression in pigs
2002
Landolt, Gabrielle | Nemke, Brett W. | Darien, Benjamin J. | Kruse-Elliott, Kris T.
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.
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