Abstract
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 language | English (US) |
|---|---|
| Pages (from-to) | 349-356 |
| Number of pages | 8 |
| Journal | Clinical Science |
| Volume | 104 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2003 |
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Keywords
- Anticoagulant
- Haemodynamics
- Infection/inflammation
- Pseudomonas aeruginosa
- Septic shock
- Thrombosis
ASJC Scopus subject areas
- Medicine(all)
Cite this
High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep. / Murakami, Kazunori; Enkhbaatar, Perenlei; Shimoda, Katsumi; Mizutani, Akio; Cox, Robert A.; Schmalstieg, Frank C.; Jodoin, Jeffrey M.; Hawkins, Hal K.; Traber, Lillian D.; Traber, Daniel L.
In: Clinical Science, Vol. 104, No. 4, 01.04.2003, p. 349-356.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep
AU - Murakami, Kazunori
AU - Enkhbaatar, Perenlei
AU - Shimoda, Katsumi
AU - Mizutani, Akio
AU - Cox, Robert A.
AU - Schmalstieg, Frank C.
AU - Jodoin, Jeffrey M.
AU - Hawkins, Hal K.
AU - Traber, Lillian D.
AU - Traber, Daniel L.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
KW - Anticoagulant
KW - Haemodynamics
KW - Infection/inflammation
KW - Pseudomonas aeruginosa
KW - Septic shock
KW - Thrombosis
UR - http://www.scopus.com/inward/record.url?scp=0037392865&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037392865&partnerID=8YFLogxK
U2 - 10.1042/CS20020258
DO - 10.1042/CS20020258
M3 - Article
C2 - 12653676
AN - SCOPUS:0037392865
VL - 104
SP - 349
EP - 356
JO - Clinical Science
JF - Clinical Science
SN - 0143-5221
IS - 4
ER -