The effects of recombinant tissue-type plasminogen activator (rt-PA) on canine cadaver lung transplantation

The intrapulmonary thrombi that form after the cessation of circulation are thought to be one of the major causes of graft function failure. We evalua ted the effect of recombinant tissue-type plasminogen activator (rt-PA) in a canine cadaver lung transplant model. Donor dogs were killed by the intra venous administration of pancuronium bromide without heparinization, and le ft for 2h at room temperature. The donor lungs were then flushed with low p otassium dextran glucose (LPDG) solution, being subjected to a total ischem ic time of 3h. Following left lung transplantation, the contralateral pulmo nary artery of the recipient dogs was ligated. In group 1 (n = 6), chloride solution was administered from the main pulmonary artery for 90 min, comme ncing 15 min prior to reperfusion. In group 2 (it = 6), 2.5 mu g/kg per min of rt-PA, and in group 3 (n = 6), 5.0 mu g/kg per min of rt-PA, were conti nuously infused in the same manner as in group 1. Lung function, including arterial blood gases and pulmonary hemodynamics, was measured for 3h. The s ide effects of rt-PA were evaluated by measuring the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, alpha(2)-plasmin inhibitor (alpha(2)-PI), plasminogen, and fibrin/fibrinogen degradation pr oduct (FDP). All of the animals in the three groups survived throughout the observation period. The group 3 animals had significantly better gas excha nge than the group 1 animals, and the pulmonary hemodynamics were significa ntly better in the group 2 and 3 animals than in the group 1 animals. The F DP 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 impro ves early lung function, particularly pulmonary hemodynamics.