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Clinical Science (2003) 104, (313–321) (Printed in Great Britain)

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P-selectin blockade fails to improve acute lung injury in sheep

Abhijit CHANDRA*, Jiro KATAHIRA*, Frank C. SCHMALSTIEG†, Kazunori MURAKAMI*, Perenlei ENKHBAATAR*, Robert A. COX‡, Hal K. HAWKINS‡, Lillian D. TRABER*, David N. HERNDON§ and Daniel L. TRABER*

*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A., †Department of Pediatrics, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A., ‡Department of Pathology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A., and §Department of Surgery, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77550, U.S.A.

Key words: acute respiratory distress syndrome (ARDS), burn, P-selectin, smoke.

Abbreviations: ARDS, acute respiratory distress syndrome; CI, cardiac index; F_iO₂, inspired fraction of O₂; MPO, myeloperoxidase; NOx, nitrate/nitrite; PaO₂, arterial partial pressure of O₂; PAP, pulmonary arterial pressure; Q_s/Q_t, intrapulmonary shunt fraction; TBSA, total body surface area.

Correspondence: Professor Daniel L. Traber (e-mail dltraber@utmb.edu).

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 ('F_iO₂') 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.

Received 17 September 2002/23 October 2002; accepted 13 December 2002

The Biochemical Society and the Medical Research Society © 2003