Clinical And Basic Research Of The Pulmonary Ischemia-Reperfusion Injury After The Deep Hypothermic Circulatory Arrest

Objective:To evaluate the prognosis and risk factors of the postoperative acute respiratory distress syndrome(ARDS)after the surgery of Stanford type A aorta dissection(AD),and provide references for prevention and treatment of such diseases.Materials: 329 patients were classified as the objects of the study who had accepted the conventional thoracotomy of Stanford type A AD from January 2013 to July 2015 in our department,and 126 cases(devided half and half into two groups named non ARDS group and ARDS groups)of them were finally included in the retrospective nested case-control study which involved age,gender,etiologogy,preoperative complications,surgical procedures,intraoperative conditions,the amount of perioperative blood transfusion,TNF-? level in serum.Suspected risk factors for postoperative ARDS after the surgery of Stanford type A AD were tested by multivariate logistics regression analysis.The motality rates,postoperative complications,prognosis,the total cost of hospitalization,the survival curves plotted and other methods were applied to assess the ARDS's influence on the prognosis of the Stanford type A AD surgery.Results: The incidence of postoperative ARDS after the surgery of Stanford type A AD was 20.7%.No significant differences were observed in age,gender,etiology,preoperative complications,the repair method of aortic arch and the extent of surgery procedure.Patients in ARDS group had experienced significantly longer CPB time and DHCA time.However,there was no significant difference in aortic cross-clamping time between the two groups.Patients in ARDS group had received more perioperative transfusion of red blood cell,platelets and fresh frozen plasma and had significantly higher incidence of pulmonary infection,MODS and mortality.The ICU stay time,mechanical ventilation time were significantly longer in patients form ARDS group,and the total cost of hospitalization of patients from ARDS group was significantly higher than those of non-ARDS group.Postoperative oxygenation index(OI)values of patients in ARDS group were observed lower than those of non-ARDS group,however,the postoperative Apache? scores were conversely higher.Patients in ARDS group showed significantly higher intensity in the serum TNF-? level than those of non-ARDS group.Multivariate logistic regression analysis showed that DHCA time,the intensity of the serum TNF-? level and perioperative blood transfusion(regardless of the types of infusion)were independent risk factors of postoperative ARDS after the surgery of Stanford type A AD.Survival curve analysis confirmed that the survival rate of patients in ARDS group after Stanford type A AD surgery were significantly lower than those of non-ARDS ARDS group.Conclusion: Postoperative ARDS after the surgery of Stanford type A AD had seriously influences in the prognosis of patients,which were closely related with the DHCA time,perioperative blood transfusion and serum TNF-? levels.Postoperative pulmonary function was expected to be improved by improving surgical techniques,reducing DHCA time,transfusion-related acute respiratory distress syndrome and serum TNF-? levels.Objective: To establish in vivo rat models with lung ischemia-reperfusion injury(LIRI)under deep hypothermic circulatory arrest(DHCA)and provided solid foundation of in vivo intervention trial.Materials: Healthy adult male SD rats with approximative body weitht were evenly divided into I/R group(n=15)and sham group(n=15)which then received general anesthesia and thoracotomy.The water bath equipment was applied to control the body temperature of the rats.Blood gas analysis,airway resistance,wet/dry(W/D)ratio,quantity and composition of the cell in BALF and pathological changes in tissue sections were evaluated to confirmed the occurance of ARDS after I/R.Results: A total of 32 rats were consumed in the following experiment including 15 cases of I/R group and sham group with the same cases.Only one case of death from hypoxemia in I/R group,and one case from sham group failed to be observed the typical performance of ARDS.Success rate of the establishment of in vivo rat models with LIRI reached 88.2%(15/17),and all cases were suvived within 12 h after surgery.Preoperative preparation and anesthesia consumed 25.5±6.4 min,surgical process consumed 41.2±9.2 min and the recovery after surgery consumed 23.6±3.2 min.Total operation time consuming 96.5±12.3 min.Conclusion: Only the left lower lobe of the rat experienced the circulatory arrest,and the simple operation which could completed by only one person without and caused little damage of the respiratory function with low mortality rate.The I/R model was convinient to copy and provided a solid foundation for the subsequent larger scale experimental intervention study.The dose of anesthetic agent,endotracheal intubation,carotid artery and the length of circulatory arrest were the key points to build the model successfully.Objective: To explore the infruences and machanisms of TNF-? in postoperative ARDS after the surgery of Stanford type A AD on the basis of the rat modle of lung ischemia-reperfusion injury after deep hypothermic circulatory arrest and to provide new target for clinical treatment.Materials: 72 male SD rats were divided into three groups named as sham group(group S,n=24),control group(group C,n=24)and experimental group(group Ab,n=24),and each group were then divided into three subgroups(4h,12 h and 24 h after the surgery)according to the time while the lung tissue specimens were taken.The experiment simulated the procedure of Stanford type A AD surgery with DHCA following with LIRI.Specific antibodies were appllied to antagonize the function of TNF-? before the surgery.The structural changes of the lung were observed in macroscopic and microscopic levels after surgery;Perioperative oxygenation and alveolar ventilation function were evaluated by the arterial blood gas analysis;The extent of pulmonary edema were measured by W/D ratio of lung;Airway resistances were assessed by reading the peak airway pressure from ventilator;Postoperative TNF-?,IL-6/10 level in serum and MPO,MDA,SOD content in the lung tissue were measured by ELISA assay;The expression level of Caspase 3/8 and NF-?B in lung tissue were detected by RT-PCR;Survival curve analysis was appllied to assess differences among three groups in survival rates.Results: Serious lungs edema,increasing airway secretions,pulmonary interstitial edema,alveolar structure damage,infiltration of inflammatory cells and red blood cells were observed in the lung tissue of rats from group C.Pathological changes above-mentioned were seldom observed in group S,and the extent of lesions in group Ab were in beteen the other two groups.Compared with group S,postoperative arterial Pa O2 significantly reduced in group C and Ab group,and the opposite situation occurred in arterial Pa CO2.Postoperative W/D ratio of lung tissue,airway resistance,apoptosis index(AI)of lung cells,the levels of TNF-? and IL-6 in the serum,the expressions of TNF-?,MPO,MDA,Caspase3/8 and NF-?B in lung tissue were significantly increased compared with those of preoperation,and the extend of the elevation in group C was significantly higher than group Ab;Compared with group S,postoperative level of IL-10 in the serum was significantly higher,and more significantly increase after surgery was observed in group Ab.No significant differences were discoveried in the level of SOD in serum after operations among three groups.A total of 85 SD-rats were subjected to the experiment and 13 cases of deaths(13/85,15.3%)(except for the deaths from anesthesia accidents or bleeding)were observed including 2 cases from group S(2/27,7.4%),7 cases from group C(7/30,23.3%)and 4 cases from group Ab(4/28,14.3%).Significant difference in the survival rate within 24 h after surgery among three groups were confirmed(u=6.751,P=0.034).Conclusion: The machanisms that TNF-? promoted postoperative ARDS after the surgery of Stanford type A AD were: breakage of alveolar oxygenation and ventilation functions through inducing pulmonary edema,direct damage through the recruitment and activation of neutrophils,indirect damage through promotion of inflammation and oxidative stress,inducing apoptosis of alveolar epithelial cells.Preoperative prophylactic application of TNF-? antagonists which could be a potential new treatment may mitigate postoperative ARDS after Stanford type A AD surgery.