Objective To identify the N6-methyladenosine (m6A)-related characteristic genes analyzed by gene clustering and immune cell infiltration in myocardial ischemia-reperfusion injury (MI/RI) after cardiopulmonary bypass through machine learning. Methods The differential genes associated with m6A methylation were screened by the dataset GSE132176 in GEO, the samples of the dataset were clustered based on the differential gene expression profile, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential genes of the m6A cluster after clustering were performed to determine the gene function of the m6A cluster. R software was used to determine the better models in machine learning of support vector machine (SVM) model and random forest (RF) model, which were used to screen m6A-related characteristic genes in MI/RI, and construct characteristic gene nomogram to predict the incidence of disease. R software was used to analyze the correlation between characteristic genes and immune cells, and the online website was used to build a characteristic gene regulatory network. Results In this dataset, a total of 5 m6A-related differential genes were screened, and the gene expression profiles were divided into two clusters for cluster analysis. The enrichment analysis of m6A clusters showed that these genes were mainly involved in regulating monocytes differentiation, response to lipopolysaccharides, response to bacteria-derived molecules, cellular response to decreased oxygen levels, DNA transcription factor binding, DNA-binding transcription activator activity, RNA polymerase Ⅱ specificity, NOD-like receptor signaling pathway, fluid shear stress and atherosclerosis, tumor necrosis factor signaling pathway, interleukin-17 signaling pathway. The RF model was determined by R software as the better model, which determined that METTL3, YTHDF1, RBM15B and METTL14 were characteristic genes of MI/RI, and mast cells, type 1 helper lymphocytes (Th1), type 17 helper lymphocytes (Th17), and macrophages were found to be associated with MI/RI after cardiopulmonary bypass in immune cell infiltration. Conclusion The four characteristic genes METTL3, YTHDF1, RBM15B and METTL14 are obtained by machine learning, while cluster analysis and immune cell infiltration analysis can better reveal the pathophysiological process of MI/RI.
Objective To observe the influences of depolarized arrest and hyperpolarized arrest on alternation of fluidity of myocardial cell membrane during cardiopulmonary bypass (CPB) and evaluate the protective effects on myocardium of hyperpolarized arrest. Methods Seventy-two felines were randomized into three groups, each group 24. Control group: 180 minutes of CPB was conducted without aortic and vena caval cross-clamping. Depolarized arrest group: hearts underwent 60 minutes of global ischemia after aortic cross-clamping (ACC) followed by 90 minutes of reperfusion. The cardioplegic solution consisted of St. Thomas solution (K+16mmol/L). Hyperpolarized arrest group: the protocol was the same as that in depolarized arrest group except that the cardioplegic solution consisted of St.Thomas solution with pinacidil (50 mmol/L,K+5mmol/L). Microviscosity, the reciprocal of fluidity of myocardial membrane was measured in all groups by using fluorescence polarization technique. (Results )Microvis cosity of myocardial cell in depolarized arrest group during ACC period was significantly higher than that before ACC and kept on rising during reperfusion period. Microviscosity of myocardial cell in hyperpolarized arrest group during ACC was trending up and reperfusion periods as well, but markedly lower compared to that in depolarized arrest group at corresponding time points(Plt;0.01). Conclusion Hyperpolarized arrest is more effective in protecting myocardial cells from ischemia-reperfusion injury than depolarized arrest during CPB by maintaining better fluidity of myocardial membrane.
Objective To study the protective effects of ulinastatin( UTI) on lung function after cardiopulmonary bypass( CPB) . Methods 42 Patients, ASA score Ⅱ ～Ⅲ, scheduled for elective cardiac valve replacement, were randomly allocated into three groups, ie. a control group, a low dose UTI group( UTI 8000U/kg) , and a high dose UTI group( UTI 12 000 U/kg) . Inspiratory pressure( PIP) , Plateau pressure ( Pplat) , alveolar-arterial oxygen pressure difference ( AaDO2 ) , static lung compliance ( Cs) and dynamic lung compliance ( Cd) were recorded before operation ( T1 ) and at 1 hour ( T2 ) , 4 hours ( T3 ) , 24 hours ( T4 ) after CPB termination. Results Compared with pre-CPB, postoperative PIP, Pplat and AaDO2 increased, and Cs and Cd decreased significantly in the control group( all P lt; 0. 05) . Compared with the control group at T2 ～T3 , postoperative PIP, Pplat, AaDO2 were significantly lower( P lt;0. 05) , and Cs and Cd were significantly higher in the two UTI groups( P lt;0. 05) . Compared with the low dose UTI group at T2 ～T3 , the PIP, Pplat and AaDO2 were significantly reduced( P lt;0. 05) , and the Cs and Cd were significantly increased in the high dose UTI group( P lt; 0. 05) . Conclusion UTI can alleviate lung injury and improve lung function during valve replacement surgery with CPB in a dose dependent manner.
Objective To assess the protective effects of a new type of leukocyte-depletion filter-1 (LD-1) on red blood cells during cardiopulmonary bypass(CPB). Methods Twelve Mongolian dogs, weight range 25-30kg, were divided into control group and leukocyte depletion group (LD group) with random number table, LD group (n=6) had our new type of leukocyte depletion filter-1 placed in venous line which was used within the first 5 minutes after onset of CPB. The control group (n=6) had no leukocyte depletion filter installed in the circuit. CPB was set up by cannulated with a venous cannula through the right atrium and with an aortic cannula after median sternotomy. Aorta was clamped at 10 minutes of CPB and released at 70 minutes of CPB. Dogs were observed for 2 hours after weaning from CPB. Blood samples were collected prior to, at 10, 40, 75 minutes, end of and 2 hours after CPB to determine circulating leukocytes, erythrocyte fragility and plasma levels of malondialdehyde(MDA), superoxide dismutase(SOD) and free hemoglobin(FHB). Results Leukocyte numbers were significantly reduced in LD group during CPB(Plt;0.01), and lower than those in control group (Plt;0.05). Plasma levels of SOD dropped after 75 minutes of CPB in control group, but those kept normal in LD group, and higher than those in control group at 2 hours after CPB (Plt;0.05, 0.01). Serum MDA and FHB levels increased sharply in two groups (Plt;0.01), but were lower in LD group than those in control group. The concentrations of NaCl when starting and complete hemolysis were also lower in LD group than those in control group at end of and 2 hours after CPB. Conclusion The new type of LD-1 used in venous line only 5 minutes after onset of CPB can decrease leukocyte counts, and reduce erythrocyte injury effectively.
Coronary artery bypass grafting has made great progress in recent years. Off-pump coronary artery bypass grafting （off-pump） can escape from many complications resulting from cardiopulmonary bypass which powered the interest of more and more surgeons, but it is more technically demanding. Conventional coronary artery bypass grafting aided by cardiopulmonary bypass （on-pump） can provide with good condition for anastomosis, and is still applied widely. The comparation of the two surgical techniques were reviewed, including graft patency, mortality, inflammatory response, influence on coagulation and anticoagulation, injury to important organs, hospital length of stay and cost, technical convertion, et al.
There is a close relationship between inflammation and coagulation response. Inflammation and coagulation are activated simultaneously during cardiopulmonary bypass, which induce postperfusion syndrome. Leukocyte depletion filter can inhibit inflammation by reducing neutrophils in circulation. But, its effects on blood conservation are limited. Aprotinin is a serine protease inhibitor, and can prevent postoperative bleeding by anti-fibrinolysis and protection of platelet function. But its effects on anti-inflammation and protection of organs are subjected to be doubted. The combination of leukocyte depletion filter and aprotinin can inhibit inflammation as well as regulate coagulation, and may exert a good protective action during cardiopulmonary bypass.
ObjectiveTo investigate the effect of different administration methods of tranexamic acid on postoperative pulmonary inflammation response during cardiopulmonary bypass (CPB).MethodsA total of 64 SD rats were included in the study. They were randomly divided into eight different groups. CPB model was established for the operation groups. The rats in the operation groups were given tranexamic acid at low (25 mg/kg), medium (50 mg/kg) or high (100 mg/kg) concentrations before or after the CPB. Blood cells count and coagulation function were assessed 1 hour after surgery. The concentration of interleukin (IL)-1β、IL-6 and tumor necrosis factor (TNF)-α in blood and lung lavage fluid were measured. The infiltration of inflammatory cells in lungs was observed by hematoxylin-eosin (HE) staining.ResultsThe concentration of inflammatory cells in the operation groups was higher than that in the control group (P<0.05). The use of tranexamic acid inhibited the increase of IL-6 and TNF-α in whole blood and lung lavage fluid due to CPB (P<0.05), but there was no significant difference among the experimental groups (P>0.05). Tranexamic acid could reduce the exudation of inflammatory cells in the lungs.ConclusionThe use of tranexamic acid can effectively reduce the release of inflammatory factors and reduce acute lung injury caused by CPB in rat models. But simply increasing the dose or changing the timing of administration is not more effective in reducing the intensity of the inflammatory response.
Objective To investigate the effect of partial liquid ventilation (PLV) with perfluorocarbon(PFC) and continuous pulmonary artery perfusion (CPP) on lung gas exchange and lung inflammatory reaction in acute lung injury(ALI) induced by cardiopulmonary bypass (CPB). Methods Eighteen of either sex piglets(weighting10.2±1.6kg) were randomly divided into three groups: Control group, CPP+CPB group (CPP group), PLV+CPP+CPB group (PLV group). Animals in control group received no treatment but conventional mechanical ventilation.In CPP group lung perfusion with oxygenated blood at 20-25ml/kg·min was given during aortic clamping. In PLV group PFC (FDC)12ml/kg was instilled into the trachea right after CPB stopping. The changes of gas exchange were mearsured before CPB and at 0h, 1h, 2h, 3h after CPB stopping. Histological sections were taken from right and left downsides of lung. Results Compared with control group, the partial pressure of oxygen in artery (PaO2) significantly increased and alveolar-aterial oxygen gradient(AaDO2) markedly decreased after 1h in PLV group(Plt;005) and partial pressure of carbon dioxide in artery (PaCO2) also became small after 3h (Plt;005).The change of gas exchange in CPP group was markedly improved. And role of lung protection of PLV was more better than that of CPP. Light microscopy: Express of intercellular adhesion molecule-1(ICAM-1) in the histopathological lesions of lung was bely positive in control group than that of PLV group and CPP group. Conclusion PLV and continuous pulmonary artery perfusion can improve the oxygenation of lung and inhibit inflammatory reaction of acute lung injury induced by CPB
Objective To study the protective effects and mechanism of intermittent ventilation on lung injury during cardiopulmonary bypass(CPB). Methods Twenty-four patients with rheumatic heart disease (RHD) were divided into two groups with random number table: treatment group (n=13),given intermittent ventilation once every 5 minutes during CPB; control group (n=11),no ventilation during CPB. Blood samples were obtained preoperatively. A bronchoalveolar lavage was performed at 2 hours after CPB. The numbers of granulocytes, total protein (TP) and tumor necrosis factor-alpha(TNF-α) content in the bronchoalveolar lavage fluids(BALF) were measured, and lung oxygenate index (OI) were measured preoperatively and 1 hour, 4 hours after CPB termination,respectively. Results The numbers of granulocytes, TP and TNF-α content of treatment group in the BALF were significantly lower than those of the control group (Plt;0.01, P=0.02,0.02),and the lung OI of treatment group at 1 hour and 4 hours after CPB termination was also significantly lower than that of the control group(Plt;0.05); a significant increase of lung OI occurred in both groups at 1 hour and 4 hours after CPB when compared with the same group at baseline before CPB(Plt;0.05). Conclusion Intermittent ventilation has the protective effects on lung injury during CPB by decreasing granulocytes adhesion and alleviating lung inflammatory reaction and endothelial cells injury.
Objective To determine the application values of gene chip technique in cardiovascular surgical clinical and research work. Microarray for gene expression profiles was used to screen out the differentially expressed genes during cardiopulmonary bypass(CPB) in peripheral blood mononuclear cell. By doing these, it was hoped that some clues in inflammatory response during CPB could be found out. Methods The patients’ oxygenated bloods were drawn immediately before onset and termination of CPB. Peripheral blood mononuclear cell (PBMC) were obtained from heparinised blood by Ficoll gradient centrifugation. The differentially expression was measured using BD AtlasTM cDNA Expression Arrays. The candidate genes were corroborated by semiquantitative reverse transcriptionpolymerase chain reaction (RT-PCR). Results Gene chip technique was successfully used in CPB study. The gene expression profiles of cytokines of PBMC during CPB were screened out. Interleukin 6 and Wnt5a were the differentially expressed genes. But the validity using semiquantitative RT-PCR found no statistically difference(P=0.888,0.135). Conclusion Microarray technique has positive application values in the study of cytokines during CPB. cDNA microarray for gene expression profiles can primarily screen out differentially expression genes during CPB. These genes may be engaged in inflammation and other pathophysiological reactions during CPB. PBMC is not the major source of cytokines during CPB.