Accumulation of neutrophils in the lung contributes to the endothelial damage in the tissue associated with acute respiratory distress syndrome. This initial recruitment of neutrophils within the pulmonary microvasculature may involve P-selectin. Thus we hypothesized that an antibody against P-selectin would reduce pulmonary damage. Sheep were chronically instrumented and prepared. The first group received 40% body surface area third-degree burns with 48 breaths of cotton smoke and 1 mg/kg of anti-(P-selectin) antibody (termed 3D4) 1h post injury (n = 5). The second group (non-treated) received the same injury but no antibody treatment (n = 6). The third group comprised of sham animals without any injury or antibody treatment (n = 6). Sheep were studied for 48h during which they were uniformly resuscitated with Ringer's lactate solution by following the Parkland formula. All the animals were mechanically ventilated. In the non-treated injured group, the arterial partial pressure of O2 (‘PaO2’)/inspired fraction of O2 (‘FiO2’) ratio dropped to 168±30 at 48h, whereas the lung lymph flow increased to an average of 46±9ml/h (10-fold of baseline). These changes were not prevented by an anti-(P-selectin) antibody. The plasma and lymph nitrate/nitrite levels were lower in the antibody-treated group than in the non-treated group. The lymph conjugated dienes were significantly lower in the treated animals. However, lung myeloperoxidase activity and lung tissue conjugated dienes were significantly increased in the treated animals compared with the non-treated injured controls. In conclusion, although the anti-(P-selectin) antibody did not protect against lung injury during the initial 48h of burn and smoke, it decreased some aspects of injury in the peripheral microcirculation.
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February 17 2003
P-selectin blockade fails to improve acute lung injury in sheep
Abhijit CHANDRA;
Abhijit CHANDRA
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Jiro KATAHIRA;
Jiro KATAHIRA
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Frank C. SCHMALSTIEG;
Frank C. SCHMALSTIEG
†Department of Pediatrics, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Kazunori MURAKAMI;
Kazunori MURAKAMI
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Perenlei ENKHBAATAR;
Perenlei ENKHBAATAR
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Robert A. COX;
Robert A. COX
‡Department of Pathology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Hal K. HAWKINS;
Hal K. HAWKINS
‡Department of Pathology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Lillian D. TRABER;
Lillian D. TRABER
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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David N. HERNDON;
David N. HERNDON
§Department of Surgery, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77550, U.S.A.
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Daniel L. TRABER
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
Correspondence: Professor Daniel L. Traber (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
September 17 2002
Revision Received:
October 23 2002
Accepted:
December 13 2002
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2003
2003
Clin Sci (Lond) (2003) 104 (3): 313–321.
Article history
Received:
September 17 2002
Revision Received:
October 23 2002
Accepted:
December 13 2002
Citation
Abhijit CHANDRA, Jiro KATAHIRA, Frank C. SCHMALSTIEG, Kazunori MURAKAMI, Perenlei ENKHBAATAR, Robert A. COX, Hal K. HAWKINS, Lillian D. TRABER, David N. HERNDON, Daniel L. TRABER; P-selectin blockade fails to improve acute lung injury in sheep. Clin Sci (Lond) 1 March 2003; 104 (3): 313–321. doi: https://doi.org/10.1042/cs1040313
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