犬肺血栓栓塞后不同时间的血气、血液动力学及血栓的病理变化

目的建立犬肺血栓栓塞症(PTE)模型;观察栓塞后不同时间犬动脉血气、血液动力学、影像学及血栓病理的变化情况。方法健康成年杂种犬16只,其中栓塞左下肺动脉的15只按随机数字表法随机分为3组,每组5只:假手术组;1周组:5段血栓柱栓塞,观察1周;2周组:5段血栓柱栓塞,观察2周。另外1只将血栓柱栓塞至右下肺动脉以证实选择性栓塞的可行性,观察2周。观察指标为动脉血气、血液动力学参数及局部肺动脉造影影像学变化。实验犬经血栓栓塞制模后肌注氨甲环酸,1、2周后解剖观察栓塞情况;应用磷钨酸苏木精染色(PTAH)观察血栓的病理变化。结果犬肺血栓栓塞前,氧合指数(PaO_2/FiO_2)为(508±58)mm Hg(1 mm Hg=0.133 kPa),栓塞1 h 后为(395±100)mm Hg;栓塞前平均肺动脉压(MPAP)为(15±3)mm Hg,栓塞1 h后为(21±4)mm Hg;肺血管阻力(PVR)栓塞前为(178±114)mm Hg·s/L,栓塞1 h后为(404±260)mm Hg·s/L,差异均有统计学意义(均 P<0.05)。实验犬肺动脉栓塞后局部肺动脉造影可见截断征;1周时见栓塞近端肺动脉明显增粗,管壁僵硬样改变等。栓塞1、2周时解剖发现实验犬肺动脉内血栓表面不平滑;PTAH 染色见血栓表面机化,2周组见血栓内多处再通,肺动脉壁增生组织包绕、分割血栓。结论将血栓柱栓塞犬肺叶动脉,并用氨甲环酸抑制纤溶,可建立模拟慢性 PTE 部分病理改变的动物模型;栓塞不同时间,肺动脉造影表现不同;时间越长,血栓机化越明显。

Effects of different durations of thromboembolism on blood gases, hemodynamics,pulmonary arteriography and thrombo-pathology in a canine model with selective embolization of pulmonary lobar arteries

OBJECTIVE: To investigate the effects of different durations of thromboembolism on blood gases, hemodynamic parameters, pulmonary arteriography and thrombo-pathology in an animal model mimicking chronic pulmonary thromboembolism (PTE). METHODS: Sixteen dogs were embolized with five thrombi developed by autologous blood into the left lower pulmonary artery (n = 15) and the right lower pulmonary artery (n = 1, used to confirm the available method of selective embolization). The 15 dogs were divided into three groups: sham group (n = 5), one-week group (n = 5) and two-week group (n = 5) according to the different durations of embolization. Swan-Ganz catheter was used to guide a plastic duct, through which the thrombi were injected selectively into the left or right lower pulmonary artery by X-ray fluoroscopy. Local pulmonary arteriography of lower pulmonary arteries was taken. Blood pressure (BP), and blood gases were measured. Central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), pulmonary arteriole wedge pressure (PAWP), and cardiac output (CO) were recorded, and pulmonary vascular resistance (PVR) was calculated. Each dog underwent muscular injection with tranexamic acid for one or two weeks to prevent thrombolysis. The lower lung lobe was dissected to confirm the thromboembolism after one or two weeks. The lung sections were stained with phosphotungstic acid hematoxyclin (PTAH) to observe thromboemboli with optical microscopy. RESULTS: In the PTE group, PaO(2)/FiO(2), MPAP and PVR changed significantly as compared to baseline values (P < 0.05) after one hour of embolization, with MPAP increasing from (15 +/- 3) mm Hg to (21 +/- 4) mm Hg, PVR increasing from (178 +/- 114) mm Hg.s/L to (404 +/- 260) mm Hg.s/L, and PaO(2)/FiO(2) decreasing from (508 +/- 58) mm Hg to (395 +/- 100) mm Hg; these parameters returned to the baseline values one or two weeks later. After embolization, pulmonary arteriography demonstrated lower lobar artery cut-off perfusion defects. One week later, pulmonary arteriography demonstrated irregularities and stiffness of the arterial wall, enlarged proximal part of lower pulmonary artery and cut-off perfusion defects. Poor filling at embolus site was evident after embolization for two weeks. In the 1-week PTE group, organized tissue covered with the blue-purple fibrin nest was observed in the thrombus with PTAH stain. In the two-week group, the well organized thrombi were partially recanalized and surrounded and invaded by hyperplastic tissues from pulmonary artery wall. CONCLUSIONS: A canine model mimicking chronic PTE can be established by the use of fibrinolytic inhibitor tranexamic acid. Different manifestations on pulmonary arteriography and varied degree of organization of thrombi are evident at different times after embolizaion.