title: Aerosolized tissue plasminogen inhibitor improves pulmonary function in sheep with burn and smoke inhalation.
abstract: Acute respiratory distress syndrome is a major complication in patients with thermal injury. The obstruction of the airway by cast material, composed in part of fibrin, contributes to deterioration of pulmonary gas exchange. We tested the effect of aerosol administration of tissue plasminogen activator, which lyses fibrin clots, on acute lung injury in sheep that had undergone combined burn/smoke inhalation injury. Anesthetized sheep were given a 40% total body surface, third degree burn and were insufflated with cotton smoke. Tissue plasminogen activator (TPA) was nebulized every 4 h at 1 or 2 mg for each nebulization, beginning 4 h after injury. Injured but untreated control sheep developed multiple symptoms of acute respiratory distress syndrome: decreased pulmonary gas exchange, increased pulmonary edema, and extensive airway obstruction. These control animals also showed increased pulmonary transvascular fluid flux and increased airway pressures. These variables were all stable in sham animals. Nebulization of saline or 1 mg of TPA only slightly improved measures of pulmonary function. Treatment of injured sheep with 2 mg of TPA attenuated all the pulmonary abnormalities noted above. The results provide evidence that clearance of airway obstructive cast material is crucial in managing acute respiratory distress syndrome resulting from combined burn and smoke inhalation injury.
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.forename: Kazunori
authors.initials: K
authors.lastname: Murakami
authors.forename: Robert
authors.initials: R
authors.lastname: Cox
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
authors.forename: Naoki
authors.initials: N
authors.lastname: Morita
authors.forename: Kimberly
authors.initials: K
authors.lastname: Brantley
authors.forename: Ann
authors.initials: A
authors.lastname: Burke
authors.forename: Hal
authors.initials: H
authors.lastname: Hawkins
authors.forename: Frank
authors.initials: F
authors.lastname: Schmalstieg
authors.forename: Lillian
authors.initials: L
authors.lastname: Traber
authors.forename: David
authors.initials: D
authors.lastname: Herndon
authors.forename: Daniel
authors.initials: D
authors.lastname: Traber
mesh_terms: D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D002056:Burns / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015849:Plasminogen Inactivators / Q000008:administration & dosage / Q000627:therapeutic use*; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000336:Aerosols; D015849:Plasminogen Inactivators