High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep

Kazunori Murakami, Perenlei Enkhbaatar, Katsumi Shimoda, Akio Mizutani, Robert A. Cox, Frank C. Schmalstieg, Jeffrey M. Jodoin, Hal K. Hawkins, Lillian D. Traber, Daniel L. Traber

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Thrombin is involved in various inflammatory responses. In sepsis, coagulation abnormalities are major complications. Acute lung iniury is one of the most life-threatening problems that can result from sepsis. We hypothesized that high-dose heparin might be effective in attenuating acute lung injury in our sepsis model. Female sheep (n = 16) were surgically prepared for the study. After a tracheotomy, 48 breaths of cotton smoke (< 40°C) were insufflated into the airway. Afterwards, live Pseudomonas aeruginosa (5 x l011 colony-forming units) bacteria were instilled into the lung. All sheep were ventilated mechanically with 100% O2, and were divided into three groups: a heparin infusion group (n = 6), a Ringer's lactate infusion group (n = 6), and a sham-injury group (n = 4; surgically prepared in the same fashion but receiving no inhalation injury or bacteria). The treatment was started 1 h after the insult, and was continued thereafter for 24 h. The dose of heparin was adjusted by monitoring to target an activated clotting time of between 300 and 400 s (baseline = approx. 150 s). Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes, including an increased cardiac output and a fall in systemic vascular resistance. There was a decrease in the arterial partial pressure of O2. In conclusion, high-dose heparin did not prevent lung dysfunction in this model, in which acute lung injury was induced by combined smoke and septic challenge.

Original languageEnglish (US)
Pages (from-to)349-356
Number of pages8
JournalClinical Science
Issue number4
StatePublished - Apr 1 2003


  • Anticoagulant
  • Haemodynamics
  • Infection/inflammation
  • Pseudomonas aeruginosa
  • Septic shock
  • Thrombosis

ASJC Scopus subject areas

  • General Medicine


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