Recombinant antithrombin attenuates pulmonary inflammation following smoke inhalation and pneumonia in sheep

Kazunori Murakami, Roy McGuire, Robert A. Cox, Jeffrey M. Jodoin, Frank C. Schmalstieg, Lillian D. Traber, Hal K. Hawkins, David Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Objective: The interaction between coagulation and inflammation has become one of the major topics in critical care medicine. In the present study, we investigated the effect of posttreatment of sepsis with recombinant human antithrombin. Design: Experimental laboratory in a university hospital. Setting: University laboratory. Subjects: Female merino ewes (n = 16). Interventions: After 1 wk of recovery from the surgical preparation, a tracheotomy was performed followed by insufflation of 48 breaths of cotton smoke (<40°C). Afterward, a stock solution of live Pseudomonas aeruginosa (5 × 1011 colony-forming units) was instilled in the both lung lobes through a bronchoscope. All sheep were mechanically ventilated employing 100% oxygen. An infusion of recombinant human antithrombin (100 units·kg-1·24 hrs-1, intravenously; n = 6) or saline (n = 6) was started 1 hr after injury. Sham control animals (n = 4) were surgically prepared but not insufflated with smoke and bacteria. Lung histologic changes were evaluated by a scoring system. Measurements and Main Results: The infusion of recombinant human antithrombin maintained the baseline antithrombin activity throughout the study; in the saline-treated group, antithrombin activity decreased significantly. The lung wet/dry weight ratio and the histology score (combined scores for congestion, edema, inflammation, and hemorrhage) were significantly increased by the insult, but recombinant human antithrombin attenuated these responses. More than 30% of both bronchi and bronchioles were obstructed by cast formation after smoke inhalation and pneumonia. The cast was composed of epithelial cells, neutrophils, mucus, and fibrin. The obstruction was significantly improved by recombinant human antithrombin infusion. Arterial pressure and urine output were also attenuated in recombinant human antithrombin-treated animals. The increases in plasma nitrate/nitrite concentrations and pulmonary shunt fraction after the injury were not attenuated by recombinant human antithrombin. Conclusion: Posttreatment by recombinant human antithrombin was effective in treating acute lung injury after smoke inhalation and pneumonia in sheep. We hypothesize that the decrease in antithrombin activity during sepsis might induce severe airway obstruction and that supplementation with antithrombin inhibits this decrease.

Original languageEnglish (US)
Pages (from-to)577-583
Number of pages7
JournalCritical Care Medicine
Volume31
Issue number2
DOIs
StatePublished - Feb 1 2003

Fingerprint

Antithrombins
Smoke
Inhalation
Sheep
Pneumonia
Lung
Sepsis
Inflammation
Bronchioles
Bronchoscopes
Tracheotomy
Insufflation
Acute Lung Injury
Wounds and Injuries
Pulmonary Edema
Airway Obstruction
Bronchi
Mucus
Critical Care
Nitrites

Keywords

  • Acute lung injury
  • Adult respiratory distress syndrome
  • Cardiovascular
  • Histology
  • Pseudomonas
  • Pulmonary
  • Recombinant antithrombin
  • Sepsis
  • Smoke inhalation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Murakami, K., McGuire, R., Cox, R. A., Jodoin, J. M., Schmalstieg, F. C., Traber, L. D., ... Traber, D. L. (2003). Recombinant antithrombin attenuates pulmonary inflammation following smoke inhalation and pneumonia in sheep. Critical Care Medicine, 31(2), 577-583. https://doi.org/10.1097/01.CCM.0000050444.52531.08

Recombinant antithrombin attenuates pulmonary inflammation following smoke inhalation and pneumonia in sheep. / Murakami, Kazunori; McGuire, Roy; Cox, Robert A.; Jodoin, Jeffrey M.; Schmalstieg, Frank C.; Traber, Lillian D.; Hawkins, Hal K.; Herndon, David; Traber, Daniel L.

In: Critical Care Medicine, Vol. 31, No. 2, 01.02.2003, p. 577-583.

Research output: Contribution to journalArticle

Murakami, K, McGuire, R, Cox, RA, Jodoin, JM, Schmalstieg, FC, Traber, LD, Hawkins, HK, Herndon, D & Traber, DL 2003, 'Recombinant antithrombin attenuates pulmonary inflammation following smoke inhalation and pneumonia in sheep', Critical Care Medicine, vol. 31, no. 2, pp. 577-583. https://doi.org/10.1097/01.CCM.0000050444.52531.08
Murakami, Kazunori ; McGuire, Roy ; Cox, Robert A. ; Jodoin, Jeffrey M. ; Schmalstieg, Frank C. ; Traber, Lillian D. ; Hawkins, Hal K. ; Herndon, David ; Traber, Daniel L. / Recombinant antithrombin attenuates pulmonary inflammation following smoke inhalation and pneumonia in sheep. In: Critical Care Medicine. 2003 ; Vol. 31, No. 2. pp. 577-583.
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N2 - Objective: The interaction between coagulation and inflammation has become one of the major topics in critical care medicine. In the present study, we investigated the effect of posttreatment of sepsis with recombinant human antithrombin. Design: Experimental laboratory in a university hospital. Setting: University laboratory. Subjects: Female merino ewes (n = 16). Interventions: After 1 wk of recovery from the surgical preparation, a tracheotomy was performed followed by insufflation of 48 breaths of cotton smoke (<40°C). Afterward, a stock solution of live Pseudomonas aeruginosa (5 × 1011 colony-forming units) was instilled in the both lung lobes through a bronchoscope. All sheep were mechanically ventilated employing 100% oxygen. An infusion of recombinant human antithrombin (100 units·kg-1·24 hrs-1, intravenously; n = 6) or saline (n = 6) was started 1 hr after injury. Sham control animals (n = 4) were surgically prepared but not insufflated with smoke and bacteria. Lung histologic changes were evaluated by a scoring system. Measurements and Main Results: The infusion of recombinant human antithrombin maintained the baseline antithrombin activity throughout the study; in the saline-treated group, antithrombin activity decreased significantly. The lung wet/dry weight ratio and the histology score (combined scores for congestion, edema, inflammation, and hemorrhage) were significantly increased by the insult, but recombinant human antithrombin attenuated these responses. More than 30% of both bronchi and bronchioles were obstructed by cast formation after smoke inhalation and pneumonia. The cast was composed of epithelial cells, neutrophils, mucus, and fibrin. The obstruction was significantly improved by recombinant human antithrombin infusion. Arterial pressure and urine output were also attenuated in recombinant human antithrombin-treated animals. The increases in plasma nitrate/nitrite concentrations and pulmonary shunt fraction after the injury were not attenuated by recombinant human antithrombin. Conclusion: Posttreatment by recombinant human antithrombin was effective in treating acute lung injury after smoke inhalation and pneumonia in sheep. We hypothesize that the decrease in antithrombin activity during sepsis might induce severe airway obstruction and that supplementation with antithrombin inhibits this decrease.

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KW - Adult respiratory distress syndrome

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