| Background and Objective: With changes in China’s social and economic change and lifestyle and the process of population aging, the risk factors for cardiovascular disease continue to grow, and its death accounts for the primacy of total mortality causes. CPB open-heart surgery is the main means of treatment for cardiac organic pathologic changes; although CPB technology has made great progress in equipment, materials and cardiac surgery technology and complications and mortality of open-heart surgery under CPB are gradually decreased, lung injury caused by low temperature, hypoperfusion and inflammatory response is still one of the common complications after CPB surgery due to its non-physiological hemodynamic characteristics. Almost all the patients after CPB have varying degrees of impaired lung function; the less severe cases only have transient symptoms, while the severe ones may have respiratory distress and even acute respiratory failure, causing irreparable consequences. In consequence, how to avoid lung injury in CPB has been the focus of attention. Currently, it has been proved that the use of vascular endothelial growth factor(VEGF) has a protective effect on ischemia-reperfusion heart and kidneys during CPB, but there is less study on whether VEGF has a protective effect on lung injury after CPB. This study has envisaged the use of ectogenic VEGF intervention to reduce lung injury after CPB, thus a CPB model for dogs is established to observe the protective effect of ectogenic VEGF on lung injury after CPB, aimed to provide a new method for the post-CPB lung protection.Methods: Nine male Beagle dogs of 12-15 kg were selected, inhibited from drinking water for 12 h before operation, and received preoperative intramuscular injection of 0.5mg atropine and after total intravenous anesthesia of 3-5mg/kg amobarbital sodium and 3mg/kg propofol. Then intubation was performed using 6.5# catheter to connect to ventilator(inhaled oxygen concentration of 100% and respiratory rate of 17 beats/min). ECG monitor was connected after femoral artery puncture and 7F Central venous catheter was inserted into internal jugular vein, used for monitoring venous pressure and pumping vasoactive drugs. General CPB was established. CPB time was 120 min, and assisted circulation after resuscitation was 30min; the CPB temperature was maintained at 32~34℃ and systemic circulation pressure on average was 60-70 mm Hg; CPB flow was 80~120ml/(kg·min), and Hct through allogenic blood transfusion was between 24% and 28%. All animals were randomly divided into sham-operation group(sham group) and control group(con group) and intervention group(vegf group). Each group had 3 dogs. 0.5g/kg normal saline was slowly injected to the veins of Sham group within 30 min before surgery and then thoracotomy and superior and inferior vena cava cannulation were performed, no CPB. 0.5g/kg normal saline was slowly injected to the veins of con group within 30 min before surgery and general CPB was120 min, while assisted circulation was 30 min. 0.5g/kg vegf was slowly injected to the veins of vegf group within 30 min before surgery and general CPB was120 min, while assisted circulation was 30 min. At the end of the experiment, the same part of the lung tissue was taken to calculate ratio of lung wet weight to dry weight(W/D), and a certain amount of lung tissue was prepared into the lung homogenates and the supernatant was taken after centrifugation to determine contents of MDA, SOD, IL-6 and TNF-α respectively. A certain amount of lung tissue was taken for fixation, section and HE staining and then pathology results were observed under light microscope.Results:1. W/D ratio: W/D ratio after CPB in con group(11.3±1.6) was significantly higher than that in the sham group(6.3±0.8),P=0.003,the difference is statistically significant;the W/D ratio in con group was significantly higher than that in the vegf group(7.8±1.2),P=0.014,the difference is statistically significant;while W/D ratio in vegf group was slightly higher than that in sham group, P=0. 114,the difference not statistically significant. 2. MDA content: The content of MDA after CPB in con group(268.121±4.424 ng/ml)was significantly greater than that in the sham group(227.336 ±3.948 ng/ml),P=0.001,the difference was statistically significant;of which MDA content in the vegf group(246.488±8.585ng/ml) was significantly higher than that in sham group,P=0.021,the difference was statistically significant;while the MDA content in the con group was significantly higher than that in vegf group,P=0.009,the difference was statistically significant.3.SOD content: The content of SOD in sham group(1622.126±36.212 ng/ml) was significantly higher than that in con group(1364.391±92.761 ng/ml),P=0.006,the difference was statistically significant; while the SOD content in the vegf group(1541.142±25.539 ng/ml) was significantly higher than that in con group,P=0.018,the difference was statistically significant;of which SOD content in sham group was slightly higher than that in vegf group,P=0.218,the difference was not statistically significant.4.IL-6 level: IL-6 level after CPB in con group(135.851±10.276 ng/ml)was significantly higher than that in sham group( 106.129±1.986 ng/ml),P=0.005,the difference was statistically significant; while the IL-6 level in the con group was significantly higher than that in vegf group(114.915±3.561 ng/ml),P=0.014,the difference was statistically significant;of which IL-6 level in vegf group was slightly higher than that in sham group,P=0.224,the difference was not statistically significant.5.TNF-α content: The content of TNF-α after CPB in con group(247.675±1.735 ng/ml) was significantly greater than that in the sham group(206.798±2.414 ng/ml),P=0.001,the difference was statistically significant; while the content of TNF-α in the vegf group(222.618±9.000 ng/ml) was significantly higher than that in sham group,P=0.032,the difference was statistically significant; of which TNF-α content in the con group was significantly higher than that in vegf group,P=0.003, the difference was statistically significant.6.Pathology of lung tissue: there was edema and congestion of lung tissue, widened alveolar septum, a large number of inflammatory cells and obvious infiltration of red cell in con group, and there was mild edema of lung tissue, infiltration of few inflammatory cells in vegf group, while the changes in pathology of lung tissue in sham group were significantly lighter than those in con group and vegf group.Conclusion: 1. this experiment has established CPB model using dogs, simple to operate, and it has effectively simulated the pathophysiologic status of human after CPB; the experiment has excellent repetition and high stability. 2.Vascular endothelial growth factor(VEGF) may reduce increased permeability of pulmonary capillaries caused by lung ischemia-reperfusion during CPB of dogs, decrease membrane lipid peroxidation and increase the body’s ability of removing free radicals. 3. VEGF has a protective effect on lung injury after CPB, which is probably because it can repair vascular endothelial injury, reduce pulmonary ischemia and hypoxia, lessen the damage of oxygen free radicals and inhibit accumulation and activation of inflammatory cytokines, so as to achieve the purpose of lung protection. |
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