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 2h at room temperature. The donor lungs were then flushed with low potassium dextran glucose (LPDG) solution, being subjected to a total ischemic time of 3h. 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 μg/kg per min of rt-PA, and in group 3 (n=6), 5.0 μg/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 3h. The side effects of rt-PA were evaluated by measuring the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, alpha₂-plasmin inhibitor (α₂-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.