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 Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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) 1 h 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 48 h 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 48 h, whereas the lung lymph flow increased to an average of 46±9 ml/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 48 h of burn and smoke, it decreased some aspects of injury in the peripheral microcirculation.

Original languageEnglish (US)
Pages (from-to)313-321
Number of pages9
JournalClinical Science
Volume104
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

P-Selectin
Acute Lung Injury
Sheep
Antibodies
Lung
Lymph
Wounds and Injuries
Smoke
Neutrophil Infiltration
Partial Pressure
Body Surface Area
Adult Respiratory Distress Syndrome
Lung Injury
Microcirculation
Nitrites
Microvessels
Burns
Nitrates
Peroxidase
Arterial Pressure

Keywords

  • Acute respiratory distress syndrome (ARDS)
  • Burn
  • P-selectin
  • Smoke

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chandra, A., Katahira, J., Schmalstieg, F. C., Murakami, K., Enkhbaatar, P., Cox, R. A., ... Traber, D. L. (2003). P-selectin blockade fails to improve acute lung injury in sheep. Clinical Science, 104(3), 313-321. https://doi.org/10.1042/CS20020244

P-selectin blockade fails to improve acute lung injury in sheep. / Chandra, Abhijit; Katahira, Jiro; Schmalstieg, Frank C.; Murakami, Kazunori; Enkhbaatar, Perenlei; Cox, Robert A.; Hawkins, Hal K.; Traber, Lillian D.; Herndon, David; Traber, Daniel L.

In: Clinical Science, Vol. 104, No. 3, 01.03.2003, p. 313-321.

Research output: Contribution to journalArticle

Chandra, A, Katahira, J, Schmalstieg, FC, Murakami, K, Enkhbaatar, P, Cox, RA, Hawkins, HK, Traber, LD, Herndon, D & Traber, DL 2003, 'P-selectin blockade fails to improve acute lung injury in sheep', Clinical Science, vol. 104, no. 3, pp. 313-321. https://doi.org/10.1042/CS20020244
Chandra A, Katahira J, Schmalstieg FC, Murakami K, Enkhbaatar P, Cox RA et al. P-selectin blockade fails to improve acute lung injury in sheep. Clinical Science. 2003 Mar 1;104(3):313-321. https://doi.org/10.1042/CS20020244
Chandra, Abhijit ; Katahira, Jiro ; Schmalstieg, Frank C. ; Murakami, Kazunori ; Enkhbaatar, Perenlei ; Cox, Robert A. ; Hawkins, Hal K. ; Traber, Lillian D. ; Herndon, David ; Traber, Daniel L. / P-selectin blockade fails to improve acute lung injury in sheep. In: Clinical Science. 2003 ; Vol. 104, No. 3. pp. 313-321.
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