| Objective To investigate the preventive and treatmental effects and the machanism of lung ischemia-reperfusion injury using retrograde pulmonary perfusion(RPP) during pulmonary embolectomy.Methods Twenty adult dogs were randomly assigned into the control group(Group A, n=10) and the retrograde pulmonary perfusion(RPP) group(Group B, n=10). All subjects were inserted autologous thrombus into outlet of right ventricle to establish models of acute massive pulmonary embolism(AMPE) under the general anaesthesia and median thoractomy. After the establishment of the AMPE model, all subjects were put on cardiopulmonary bypass(CPB) and cardiac arrest. To Group A, standard pulmonary embolectomy was implemented, and then pulmonary incision was closed. To Group B, after thrombotic material was extracted through a pulmonary arteriotomy, RPP was conducted by using crystal liquid through left atrium to trunk pulmonary artery. Make sure that there was no significant difference in the CPB time of all subjects during the operation. The changes of hemodynamics were recorded before, after the establishment of the AMPE model, and 2 hours after CPB ceasing. The activity of MPO, MDA, SOD and the protein concentration in bronchoalveolar lavage fluid were tested after the lung tissue was harvested. The ratio between wet weight and dry weight, the apoptosis index of alveolar epithelial cells were calculated, and the pathological changes of lung tissue were observed after the biopsy was made, too. All indicators were conducted to evaluate the protective and treatmental effects of RPP on lung ischemia-perfusion injury tissue.Results 1. The models of AMPE in all subjects were successfully established, and the hemodynamics reached to the standard of acute massive pulmonaryembolism(systolic blood pressure <90mm Hg or systolic blood pressure dropped more than 40 mm Hg for at least 15 minutes). Two subjects in Group A got shock, and two in Group B got in shock, too. Right ventricle expanded drasticly after the insertion of autologous thrombus. Various parts of pulmonary artery were occupied by the low-density lesions, which resulted in the defects of pulmonary artery in pulmonary angiography. There were no statistical differences between Group A and Group B in the indexes such as systolic pulmonary artery pressure(13.3 ± 2.36 mm Hg vs 13.2 ± 2.1mm Hg, P=0.758), mean pulmonary artery pressure(9.3 ± 1.49 mm Hg vs 9.4 ± 1.08 mm Hg, P=0.395), pulmonary vascular resistance(166.22 ± 28.49 dyn.s.cm-5 vs 163.4 ± 25.28 dyn.s.cm-5, P=0.712), cardiac index(6.02 ± 0.45 L.min-1.m-2 vs 6.19 ± 0.34 L.min-1.m-2, P=0.566) and Oxygenation index(311.73 ± 20.77 vs 308.8 ± 20.83, P=0.885) before embolism. After the insertion of autologous thrombus, the s PAP(60.5 ± 6.62 mm Hg vs 13.3 ± 2.36 mm Hg, P<0.001), m PAP(46.5 ± 6.13 mm Hg vs 9.3 ± 1.49 mm Hg, P<0.001), PVR(1541.45 ± 188.53 dyn.s.cm-5 vs 166.22 ± 28.49 dyn.s.cm-5, P<0.001), CI(3.22 ± 0.37 L.min-1.m-2 vs 6.02 ± 0.45 L.min-1.m-2, P<0.001) and Oxygenation index(169.77 ± 7.94 vs 311.73 ± 20.77, P<0.001) changed evidently in Group A. The s PAP(58.4±5.91 mm Hg vs 13.20±2.1mm Hg, P<0.001), m PAP(45.7 ± 5.29 mm Hg vs 9.4 ± 1.07 mm Hg, P=0.003), PVR(1426.49 ± 196.74 dyn.s.cm-5 vs 163.4 ± 25.28 dyn.s.cm-5, P<0.001), CI(3.45 ± 0.36 L.min-1.m-2 vs 6.19 ± 0.34 L.min-1.m-2, P<0.001) and Oxygenation index(170.78 ± 9.85 vs 308.80 ± 20.83, P=0.008) changed distinctly in Group B, too. The indexes of all subjects,such as s PAP(59.45 ± 5.82 mm Hg vs 13.25 ± 2.23 mm Hg, P<0.001), m PAP(46.1 ± 5.59 mm Hg vs 9.35 ± 1.27 mm Hg, P<0.001), PVR(1483.97 ± 192.31 dyn.s.cm-5 vs 164.81 ± 26.86 dyn.s.cm-5, P<0.001), CI(3.34 ± 0.36 L.min-1.m-2 vs 6.11 ± 0.37 L.min-1.m-2, P<0.001) and Oxygenation index(170.28 ± 8.72 vs 310.27 ± 20.3, P<0.001) changed obviously. There were no differences between Group A and Group B in the indexes such as s PAP(60.5 ± 6.62 mm Hg vs 58.40 ± 1.87 mm Hg, P=0.865), m PAP(46.5±6.13 mm Hg vs 45.7 ± 5.29 mm Hg, P=0.486), PVR(1541.45±188.53 dyn.s.cm-5 vs 1426.49 ± 196.74 dyn.s.cm-5, P=0.889), CI(3.22 ± 0.37 L.min-1.m-2 vs 3.45 ± 0.36 L.min-1.m-2, P=0.899) and Oxygenation index(169.77± 7.94 vs 170.78 ± 9.85, P=0.449) after the insertion of autologous thrombus.2. Two hours after CPB ceasing, the hemodynamics and Oxygenation index were monitored. In Group A, s PAP(27.3 ± 1.95 mm Hg vs 60.5 ± 6.62 mm Hg, P<0.01), m PAP(23.2 ± 1.81 mm Hg vs 46.5 ± 6.13 mm Hg, P<0.01), PVR(565.32 ± 60.18 dyn.s.cm-5 vs 1541.45 ± 188.53 dyn.s.cm-5, P<0.01), CI(4.41 ± 0.43 L.min-1.m-2 vs 3.22 ± 0.37 L.min-1.m-2, P<0.01) and Oxygenation index(209.39 ± 8.86 vs 169.77 ± 7.94, P=0.021) changed evidently. The s PAP(19.1 ± 1.79 mm Hg vs 58.4 ± 1.87 mm Hg, P<0.01), m PAP(13.8 ± 1.23 mm Hg vs 45.7 ± 5.29 mm Hg, P<0.01), PVR(269.32 ± 24.67 dyn.s.cm-5 vs 1426.49 ± 196.74 dyn.s.cm-5, P<0.01), CI(5.48 ± 0.22 L.min-1.m-2 vs 3.45 ± 0.36 L.min-1.m-2, P<0.01) and Oxygenation index(237.45 ± 18.36 vs 170.78 ± 9.85, P=0.038) changed distinctly in Group B, too. There were no differences between the Group A and Group B in the indexes such as s PAP(27.3 ± 1.95 mm Hg vs 19.1 ± 1.79 mm Hg, P=0.652), m PAP(23.2±1.81 mm Hg vs 13.8 ± 1.23 mm Hg, P=0.352), but with differences in PVR(565.32 ± 60.18 dyn.s.cm-5 vs 269.32 ± 24.67 dyn.s.cm-5, P<0.01), CI(4.41 ± 0.43 L.min-1.m-2 vs 5.48 ± 0.22 L.min-1.m-2, P=0.046) and Oxygenation Index(209.39 ± 8.86 vs 237.45 ± 18.36, P=0.034).3. Six hours after trachea cannula extraction, the lung tissue was obtained and tested. There were statistical differences between Group A and Group B in the activity of MPO(0.944 ± 0.067U/g vs 0.811 ± 0.062U/g, P=0.005), MDA(7.318 ± 0.327nmol/mg prot vs 6.765 ± 0.18nmol/mg prot, P=0.005), SOD(139.199 ± 2.51U/mg prot vs 154.912 ± 3.882U/mg prot, P=0.007), and the protein concentration in bronchoalveolar lavage fluid(1991.87 ± 85.95pg/ml vs 1877.85 ± 59.11pg/ml, P=0.005). The ratio between wet weight and dry weight had significant difference between Group A and Group B(2.2 ± 0.2 vs 3.2 ± 0.7, P=0.008).4. Six hours after trachea cannula extraction, lung tissue was harvested. The pathological sections of samples indicated that more neutrophile granulocyte accumulated and more apoptosis of alveolar epithelial cells occured in Group A than Group B. There was significant difference between Group A and Group B in the apoptosis index of alveolar epithelial cells(8.67 ± 0.61 vs 6.98 ± 0.74, P<0.001).Conclusion 1. It is practical and effective to establish the model of acute massive pulmonary embolism by inserting autologous clots into outlet of right ventricle directly using self-made device under the general anaesthesia and median thoractomy. This method to build AMPE model is invented by us, and it is the first time to be reported.2. Adopting retrograde pulmonary perfusion(RPP) during pulmonary embolectomy can flush more thrombus and air entrapped in pulmonary artery than not adopting RPP. RPP helps decrease aggregation of neutrophil cells,reduce generation of oxygen free radical and alleviate apoptosis of alveolar epithelial cells, thus mitigating lung ischemia-reperfusion injury(LIRI) and preventing from pulmonary edema and persistent pulmonary hypertension effectively.3. Retrograde pulmonary perfusion can be a more efficacious and safer strategy to treat central type and peripheral type of acute massive pulmonary embolism. |
PDF Full Text Request