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

Abstract

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.