Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation

Perenlei Enkhbaatar, Robert A. Cox, Lillian D. Traber, Martin Westphal, Esechie Aimalohi, Naoki Morita, Donald Prough, David Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

OBJECTIVE: Acute lung injury is a detrimental complication for victims of burn accidents. Airway obstruction plays an important role in pulmonary dysfunction in these patients. In this study, we tested the hypothesis that aerosolized anticoagulants will reduce the degree of airway obstruction and improve pulmonary function in sheep with severe combined burn and smoke inhalation injury by preventing the formation of airway fibrin clots. DESIGN: Prospective, randomized, controlled, experimental animal study. SETTING: Investigational intensive care unit at a university hospital. SUBJECTS: Adult female sheep. INTERVENTIONS: After 7 days of surgical recovery, sheep were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, <40°C) under halothane anesthesia. After injury, sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Sheep were randomly divided into five groups: sham, noninjured and nontreated (n = 6); control, injured and aerosolized with saline (n = 6); recombinant human antithrombin (rhAT) + heparin, injured and aerosolized with rhAT (290 units for each) and heparin (10,000 units for each) (n = 6); rhAT, injured and aerosolized with rhAT alone (290 units for each; n = 5); and heparin, injured and aerosolized with heparin alone (10,000 units for each; n = 5). rhAT and heparin were aerosolized every 4 hrs, starting at 2 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary hemodynamics were monitored during a 48-hr experimental time period. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and extensive airway obstruction. These variables were stable in sham animals. The aerosolization of rhAT or heparin alone did not significantly improve deteriorated pulmonary gas exchange. However, aerosolization of these anticoagulants in combination significantly attenuated all the observed pulmonary pathophysiology. CONCLUSIONS: The results provide definitive evidence that aerosolized rhAT and heparin in combination may be a novel treatment strategy for pulmonary pathology in burn victims with smoke inhalation injury.

Original languageEnglish (US)
Pages (from-to)2805-2810
Number of pages6
JournalCritical Care Medicine
Volume35
Issue number12
DOIs
StatePublished - Dec 2007

Fingerprint

Inhalation Burns
Antithrombins
Acute Lung Injury
Smoke
Anticoagulants
Heparin
Sheep
Smoke Inhalation Injury
Airway Obstruction
Pulmonary Gas Exchange
Lung
Lung Compliance
Halothane
Pulmonary Edema
Mechanical Ventilators
Fibrin
Accidents
Intensive Care Units
Anesthesia
Hemodynamics

Keywords

  • Acute respiratory distress syndrome
  • Airway obstruction
  • Anticoagulant
  • Burn
  • Fibrin
  • Smoke

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation. / Enkhbaatar, Perenlei; Cox, Robert A.; Traber, Lillian D.; Westphal, Martin; Aimalohi, Esechie; Morita, Naoki; Prough, Donald; Herndon, David; Traber, Daniel L.

In: Critical Care Medicine, Vol. 35, No. 12, 12.2007, p. 2805-2810.

Research output: Contribution to journalArticle

Enkhbaatar, Perenlei ; Cox, Robert A. ; Traber, Lillian D. ; Westphal, Martin ; Aimalohi, Esechie ; Morita, Naoki ; Prough, Donald ; Herndon, David ; Traber, Daniel L. / Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation. In: Critical Care Medicine. 2007 ; Vol. 35, No. 12. pp. 2805-2810.
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AU - Morita, Naoki

AU - Prough, Donald

AU - Herndon, David

AU - Traber, Daniel L.

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N2 - OBJECTIVE: Acute lung injury is a detrimental complication for victims of burn accidents. Airway obstruction plays an important role in pulmonary dysfunction in these patients. In this study, we tested the hypothesis that aerosolized anticoagulants will reduce the degree of airway obstruction and improve pulmonary function in sheep with severe combined burn and smoke inhalation injury by preventing the formation of airway fibrin clots. DESIGN: Prospective, randomized, controlled, experimental animal study. SETTING: Investigational intensive care unit at a university hospital. SUBJECTS: Adult female sheep. INTERVENTIONS: After 7 days of surgical recovery, sheep were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, <40°C) under halothane anesthesia. After injury, sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Sheep were randomly divided into five groups: sham, noninjured and nontreated (n = 6); control, injured and aerosolized with saline (n = 6); recombinant human antithrombin (rhAT) + heparin, injured and aerosolized with rhAT (290 units for each) and heparin (10,000 units for each) (n = 6); rhAT, injured and aerosolized with rhAT alone (290 units for each; n = 5); and heparin, injured and aerosolized with heparin alone (10,000 units for each; n = 5). rhAT and heparin were aerosolized every 4 hrs, starting at 2 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary hemodynamics were monitored during a 48-hr experimental time period. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and extensive airway obstruction. These variables were stable in sham animals. The aerosolization of rhAT or heparin alone did not significantly improve deteriorated pulmonary gas exchange. However, aerosolization of these anticoagulants in combination significantly attenuated all the observed pulmonary pathophysiology. CONCLUSIONS: The results provide definitive evidence that aerosolized rhAT and heparin in combination may be a novel treatment strategy for pulmonary pathology in burn victims with smoke inhalation injury.

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