title: The effects of recombinant tissue-type plasminogen activator (rt-PA) on canine cadaver lung transplantation.
abstract: The intrapulmonary thrombi that form after the cessation of circulation are thought to be one of the major causes of graft function failure. We evaluated the effect of recombinant tissue-type plasminogen activator (rt-PA) in a canine cadaver lung transplant model. Donor dogs were killed by the intravenous administration of pancuronium bromide without heparinization, and left for 2 h at room temperature. The donor lungs were then flushed with low potassium dextran glucose (LPDG) solution, being subjected to a total ischemic time of 3 h. Following left lung transplantation, the contralateral pulmonary artery of the recipient dogs was ligated. In group 1 (n = 6), chloride solution was administered from the main pulmonary artery for 90 min, commencing 15 min prior to reperfusion. In group 2 (n = 6), 2.5 microg/kg per min of rt-PA, and in group 3 (n = 6), 5.0 microg/kg per min of rt-PA, were continuously infused in the same manner as in group 1. Lung function, including arterial blood gases and pulmonary hemodynamics, was measured for 3 h. The side effects of rt-PA were evaluated by measuring the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, alpha2-plasmin inhibitor (alpha2-PI), plasminogen, and fibrin/fibrinogen degradation product (FDP). All of the animals in the three groups survived throughout the observation period. The group 3 animals had significantly better gas exchange than the group 1 animals, and the pulmonary hemodynamics were significantly better in the group 2 and 3 animals than in the group 1 animals. The FDP levels in the group 2 and 3 animals were significantly higher than those in the group 1 animals, while the PT and APTT were significantly prolonged in the group 3 animals. These findings led us to conclude that rt-PA improves early lung function, particularly pulmonary hemodynamics.
authors.affiliation: Department of Surgery II, Okayama University Medical School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Akasaka
authors.forename: H
authors.initials: H
authors.lastname: Nishi
authors.forename: M
authors.initials: M
authors.lastname: Aoe
authors.forename: H
authors.initials: H
authors.lastname: Date
authors.forename: A
authors.initials: A
authors.lastname: Andou
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002102:Cadaver; D004285:Dogs; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007511:Ischemia; D016040:Lung Transplantation / Q000379:methods*; D010314:Partial Thromboplastin Time; D010958:Plasminogen / Q000032:analysis; D011517:Prothrombin Time; D011655:Pulmonary Embolism / Q000517:prevention & control*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D000979:alpha-2-Antiplasmin / Q000032:analysis
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D000979:alpha-2-Antiplasmin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator