Combined anticoagulants ameliorate acute lung injury in sheep after burn and smoke inhalation

Perenlei Enkhbaatar, Aimalohi Esechie, Jianpu Wang, Robert A. Cox, Yoshimitsu Nakano, Atsumori Hamahata, Matthias Lange, Lillian D. Traber, Donald S. Prough, David N. Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Burn and smoke inhalation-related multiple organ dysfunction is associated with a severe fall in the plasma concentration of antithrombin. Therefore the aim of the present study was to test the hypothesis that intravenous administration of recombinant human antithrombin in combination with aerosolized heparin will ameliorate acute lung injury in sheep exposed to cutaneous burn and smoke inhalation. Sheep were prepared operatively for study and, 7 days post-surgery, sheep were given a cutaneous burn (40% of total body surface area, third-degree burn) and insufflated with cotton smoke (48 breaths, <40°C) under halothane anaesthesia. After injury, sheep were placed on a ventilator and resuscitated with Ringer's lactate solution. The animals were divided into three groups: sham group (non-injured and non-treated; n = 6), saline group (injured and received saline; n = 6) and rhAT.iv. + Hep group [injured and treated with rhAT (recombinant human antithrombin) and heparin; n = 6]. In the rhAT.iv. + Hep group, rhAT was infused continuously for 48 h starting 1 h post-injury with a dose of 0.34 mg·h-1·kg-1 of body weight and heparin (10 000 units) was aerosolized every 4 h starting at 1 h post-injury. The experiment lasted 48 h. Haemodynamics were stable in sham group, whereas the saline-treated sheep developed multiple signs of acute lung injury, including decreased pulmonary gas exchange, increased inspiratory pressures, extensive airway obstruction and increased pulmonary oedema. These pathological changes were associated with a severe fall in plasma antithrombin concentration, lung tissue accumulation of leucocytes and excessive production of NO. Treatment of injured sheep with anticoagulants attenuated all of the pulmonary pathophysiology observed. In conclusion, the results provide definitive evidence that anticoagulant therapy may be a novel and effective treatment tool in the management of burn patients with concomitant smoke inhalation injury.

Original languageEnglish (US)
Pages (from-to)321-329
Number of pages9
JournalClinical Science
Volume114
Issue number3-4
DOIs
StatePublished - Feb 2008

Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome (ARDS)
  • Antithrombin
  • Burn
  • Heparin
  • Smoke inhalation

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Enkhbaatar, P., Esechie, A., Wang, J., Cox, R. A., Nakano, Y., Hamahata, A., Lange, M., Traber, L. D., Prough, D. S., Herndon, D. N., & Traber, D. L. (2008). Combined anticoagulants ameliorate acute lung injury in sheep after burn and smoke inhalation. Clinical Science, 114(3-4), 321-329. https://doi.org/10.1042/CS20070254