title: 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 degrees C) were insufflated into the airway. Afterwards, live Pseudomonas aeruginosa (5 x 10(11) colony-forming units) bacteria were instilled into the lung. All sheep were ventilated mechanically with 100% O(2), 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 O(2). 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.
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, TX 77555, U.S.A.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Murakami
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shimoda
authors.forename: Akio
authors.initials: A
authors.lastname: Mizutani
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cox
authors.forename: Frank C
authors.initials: FC
authors.lastname: Schmalstieg
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jodoin
authors.forename: Hal K
authors.initials: HK
authors.lastname: Hawkins
authors.forename: Lillian D
authors.initials: LD
authors.lastname: Traber
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006400:Hematocrit; D006493:Heparin / Q000008:administration & dosage*; D023421:Models, Animal; D009569:Nitric Oxide / Q000097:blood; D018410:Pneumonia, Bacterial / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D017211:Treatment Failure; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000991:Antithrombins; D005338:Fibrin Fibrinogen Degradation Products; D009569:Nitric Oxide; D006493:Heparin