| Objectivea. To establish a canine model of acute submassive pulmonary embolism(SMPE) with the method of interventional embolization and to evaluate the feasibility and stability of the animal model.b. To study the efficacy and safety of intra-arterial thombolysis with different doses of urokinase(UK) for the treatment of acute SMPE.Materials and Methodsa. In 8 anaesthetized adult dogs, autologous thrombi were injected into the left inferior lobar artery by the means of interventional catheterization. Blood gases, coagulation tests, pulmonary artery pressure and angiographic blood flow were monitored before and 2 hours after the embolization. all animals were autopsied to assess the macro- and micro- change of the lung after the angiography..b. In 32 anaesthetized adult dogs, autologous thrombi were injected into the left inferior lobar artery by the means of interventional catheterization. The animals were randomly divided into four groups with equal numbers which received different treatment: Group A, for control; Group B, for thrombolysis (5000U/Kg UK), Group C, for thrombolysis (10,000U/Kg UK); Group D, for thrombolysis (20,000U/Kg UK). Blood gases, coagulation tests, pulmonary artery pressure and angiographic blood flow were registered at different timepoints during the study. animals of each group were autopsied to assess the macro- and micro- change of the lung before and after the thrombolysis.Resultsa. The SMPE models were successfully established in all animals. After embolization, the left inferior lobar artery was completely occluded in angiography. MPAP and D-dimer increased obviously, which showed statistical significance compared with the values before embolization(P<0.05). The autoposy confirmed that there was dark red thrombus in the left inferior lobar atery; under the microscope, a little exudation in the alveoli of lung and no obvious necrosis of cells were observed and the thickening of alveolar septum and infiltration of inflammatory cells were also noticed.b. The establishment of SMPE models was successfully performed in 32 dogs. The MPAP and PaO2 showed statistical significance compared with the values before embolization in the same group(P<0.01), while there is no statistical significance among the groups(P>0.05).â‘¡After thrombolysis, when compared with the control group, only the values of MPAP and PaO2 in Group C and Group D showed statistical significance (P<0.05). There was no statistical significance between Group C and Group D (P>0.05). PT and APTT prolonged at various degrees in the 3 treatment groups. Only the data in Group B showed no statistical significance compared with those in the control group (P>0.05). The PT and APTT in Group D were significantly longer than those in Group C (P<0.05). In angiography, the angiographic index before and after the embolization had statistical significance in all groups (P<0.05). After thrombolysis , the blood flow of the left inferior lobar artery improved significantly in Group C and Group D when compared with the control group (P<0.05), though there was no statistical significance between themselves (P>0.05). The result of the autopsy of Group A was similar to that of the SMPE animal model described above. In group B, there was full of dark red thrombus in the left inferior segmental arteries; under the microscope, alveolar atrophy and the thickening of alveolar septum were observed. In Group C and Group D, the left inferior lobar artery became patent and only a few thrombi could be seen in some segmental or sub-segmental vessels. In Group D, there was some hemorrhage areas in the lung, which had no regular rims and no obvious atrophy. The thickening of alveolar septum and intra-alveolar hemorrhage were noticed under microscope.ConclusionsUsing the interventional emoblization techniques to establish a canine model of acute SMPE has several advantages: easy in practice, minimally invasive, good control of the extent of embolization and etc. The model's successful establishment provides an ideal platform for the research of pulmonary embolism. The intra-aterial UK infusion within two hours after the onset of acute SMPE in canine is effective in lysing the clot and recanalising the involved pulmonary arteries when the dose of UK is appropriate. In our study, the dose of 10, 000U/kg is considered as the most rational which is quite effective with lower bleeding complications. |
