Thrombin is involved in various inflammatory responses. In sepsis, coagulation abnormalities are major complications. Acute lung injury 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 (5×1011 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 1h after the insult, and was continued thereafter for 24h. The dose of heparin was adjusted by monitoring to target an activated clotting time of between 300 and 400s (baseline = approx. 150s). 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.
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March 06 2003
High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep
Kazunori MURAKAMI;
Kazunori MURAKAMI
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Perenlei ENKHBAATAR;
Perenlei ENKHBAATAR
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Katsumi SHIMODA;
Katsumi SHIMODA
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Akio MIZUTANI;
Akio MIZUTANI
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Robert A. COX;
Robert A. COX
†Department of Pathology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Frank C. SCHMALSTIEG;
Frank C. SCHMALSTIEG
‡Department of Pediatrics, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Jeffrey M. JODOIN;
Jeffrey M. JODOIN
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Hal K. HAWKINS;
Hal K. HAWKINS
†Department of Pathology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Lillian D. TRABER;
Lillian D. TRABER
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
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Daniel L. TRABER
*Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
Correspondence: Professor Daniel L. Traber, Department of Anesthesiology, The University of Texas Medical Branch, 610 Texas Avenue, Galveston, TX 77555-0833, U.S.A. (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
September 26 2002
Revision Received:
October 25 2002
Accepted:
January 03 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2003
2003
Clin Sci (Lond) (2003) 104 (4): 349–356.
Article history
Received:
September 26 2002
Revision Received:
October 25 2002
Accepted:
January 03 2003
Citation
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; High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep. Clin Sci (Lond) 1 April 2003; 104 (4): 349–356. doi: https://doi.org/10.1042/cs1040349
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