Although the lung injury caused by cardiopulmonary bypass(CPB)has been extensively investigated,the incidence and mortality of lung injury after CPB remain a prominent clinical problem.The poor outcome has been attrib...Although the lung injury caused by cardiopulmonary bypass(CPB)has been extensively investigated,the incidence and mortality of lung injury after CPB remain a prominent clinical problem.The poor outcome has been attributed to multifactorial etiology,including the systemic inflammatory response and ischemia reperfusion(I/R)injury during CPB.Lung injury after CPB is a complex pathophysiological process and has many clinical manifestations of mild to severe disease.Which is associated with prognosis.To alleviate this lung injury,interventions that address the pathogenesis are particularly important.This review summarizes the pathogenesis,mechanism and treatment options of lung injury after CPB,such as lung protection with intralipid.展开更多
Objective： To explore the role of polymorphonuclear neutrophils （PMN） activation in lung injury following cardiopulmonary bypass （CPB）. Methods： Twenty four cases of patients with rheumatic heart disease were en...Objective： To explore the role of polymorphonuclear neutrophils （PMN） activation in lung injury following cardiopulmonary bypass （CPB）. Methods： Twenty four cases of patients with rheumatic heart disease were enrolled in this study to detect the situation of PMN activation and the degree of lung injury. Bronchoalveolar lavage fluid （BALF） and blood samples were collected just after anaesthesia and 4 h postoperatively. Related clinic data were recorded. Results： This cohort included 4 male and 20 female with age ranging from 29 to 69 years old, and body mass from 37 to 73 kg. Mean cardiopulmonary bypass time was （106.46±33.58） rain, mean cross clamp time was （77.58_＋28.02） rain, and mean mechanical ventilation time was （24.17±30.90） h. Postoperative PaO2/FiO2 decreased significantly than that during preoperation （P=0.000）. The postoperative WBC counts in peripheral blood and in BALF were both increased significantly than those during preoperation. And the postoperative rates of PMN in BALF were also increased significantly. Postoperative neutriphil elastase （NE） and myeloperoxidase （MPO） released from inflammatory ceils were increased significantly （P=0.000） both in plasma and BALF. The postoperative yon Willebrand factor （vWF） concentration in plasma was also increased significantly （P=0.000）. The postoperative concentration of sLPI in plasma was decreased, whereas it was increased significantly in BALF. Furthermore, there was a negative correlation between NE and PaO2/FiO2 both in BALF and in plasma. A negative correlation was present between vWF in plasma and PaO2/FiO2. A positive correlation was found between sLPI in plasma and PaO2/FiO2. Conclusion： PMN is recruited and activated after CPB and released large quantity of proteases, and lead to lung injury, sLPI is an important protective factor against inflammatory injury.展开更多
Objective To study if using autologous lung as a substitute of oxygenator in cardiopulmonary bypass is better than the conventional cardiopulmonary bypass with artificial oxygenator in pulmonary preservation. Methods ...Objective To study if using autologous lung as a substitute of oxygenator in cardiopulmonary bypass is better than the conventional cardiopulmonary bypass with artificial oxygenator in pulmonary preservation. Methods Twelve piglets were randomly divided into two groups （ n = 6）. The isolated lung perfusion model was established. The experimental animals underwent continuous lung perfusion for about 120 rain. While the control animals underwent 90 rain lung ischemia followed by 30 rain reperfusion. Another 12 piglets were randomly divided into two groups （ n =6）. The experimental animals underwent bi-ventricular bypass with autologous lung perfusion. While control animals underwent conventional cardiopulmonary bypass with artificial oxygenator. The bypass time and aortic cross clamping time were 135 rain and 60 rain respectively for each animal. The lung static compliance （Cstat）, alveolus-artery oxygen difference （PA-aO2 ） , TNF-α, IL-6 and wet to dry lung weight ratio （W/D） were measured. Histological and ultra-structural changes of the lung were also observed after bypass. Results After either isolated lung perfusion or cardiopulmonary bypass, the Cstat decreased, the PA-aO2 increased and the content of TNF-α increased for both groups, but the changes of experimental group were much less than those of control group. The lower W/D ratio and mild pathological changes in experimental group than those in control group were also demonstrated. Conclusion Autologous lung is able to tolerate the nonpulsatile perfusion. It can be used as a substitute to artificial ogygenator in cardiopulmonary bypass to minimize the inflammatory pulmonary injury caused mainly by ischemic reperfusion and interaction of the blood to the non-physiological surface of artificial oxygenator.展开更多
Objective To testify the lung injury induced by cardiopulmonary bypass(CPB) in canine model and observe the influence of CPB on the aquaporin 1 (AQP1) mRNA expression in canine lung. Methods 8 mongrel dogs were used t...Objective To testify the lung injury induced by cardiopulmonary bypass(CPB) in canine model and observe the influence of CPB on the aquaporin 1 (AQP1) mRNA expression in canine lung. Methods 8 mongrel dogs were used to perform the cardiopulmonary bypass. The hearts arrested for 90 minutes with mild hypothermia and rebeated for 6 hours. The hemodynamics,the ratio of lung dry weight and wet weight,the plasmic展开更多
Acute kidney injury (AKI) is defined by 0.3 mg/dL increase in serum creatinine (SCr) and is associated with higher incidence of postoperative mortality after coronary artery bypass graft (CABG). There are few clinical...Acute kidney injury (AKI) is defined by 0.3 mg/dL increase in serum creatinine (SCr) and is associated with higher incidence of postoperative mortality after coronary artery bypass graft (CABG). There are few clinical studies on the effect of dexmedetomidine (DEX) on renal function. We evaluated AKI after coronary artery bypass graft with and without cardiopulmonary bypass (CPB) under anesthesia with DEX. Method: In this retrospective study, we performed serial analysis of serum creatinine (SCr) up to 48 hours after surgery in 286 patients who underwent CABG. We tested the similarities between groups, evaluating patients separately for use of CPB and DEX. Each patient was evaluated for his or her SCr at the following points in time: preoperative, immediately postoperative, 24 hours postoperative, and 48 hours postoperative. Preoperative SCr was used as the baseline value for each patient. If the SCr increased ≥0.3 mg/dL in at least one of the periods, the patient was classified as having AKI. We also assessed the risk for AKI in patients with altered preoperative SCr (values between 1.1 to 2.0 mg/dL for women or 1.3 to 2.0 mg/dL for men) compared to patients with normal SCr. Results: The groups were similar for preoperative weight, age, and altered SCr. Patients were anesthetized with DEX and who underwent CPB exhibited higher incidence of AKI (p = 0.043). Without CPB, there was higher incidence of AKI after using DEX (p = 0.066). Conclusion: Anaesthesia with DEX increased the incidence of AKI after myocardial revascularization surgery in patients who underwent CPB.展开更多
Acute respiratory failure after surgery for aortic dissection is a serious complication that has been associated with increased mortality and morbidity. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is r...Acute respiratory failure after surgery for aortic dissection is a serious complication that has been associated with increased mortality and morbidity. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is reported as one of the treatments for this life-threatening complication. A 78-year-old male patient was admitted to our hospital for Stanford type A acute aortic dissection. He underwent emergency replacement of the ascending aorta, after which he developed acute lung injury. It was difficult to maintain oxygenation with a respirator mask. Therefore, VV-ECMO was initiated on postoperative day 1. The oxygenation gradually improved, and VV-ECMO was continued until postoperative day 13. On postoperative day 25, mechanical ventilation was withdrawn. The patient was discharged from the hospital on postoperative day 149. We report a case of successful treatment of acute lung injury with VV-ECMO initiated after surgery for aortic dissection. VV-ECMO can be considered as a treatment option for severe acute lung injury after surgery for aortic dissection.展开更多
Background It has found that ischemic postconditioning （IPO） might decrease pulmonary ischemia/reperfusion （I/ R） injury,which is one of the main reasons of lung injury caused by cardiopulmonary bypass （CPB）.It ...Background It has found that ischemic postconditioning （IPO） might decrease pulmonary ischemia/reperfusion （I/ R） injury,which is one of the main reasons of lung injury caused by cardiopulmonary bypass （CPB）.It was found that aquaporins （AQPs） play a role in the maintenance of fluid homeostasis.But it is still unclear whether IPO influences the expression of aquaporin-1 （AQP1）.This study was designed to investigate whether IPO can reduce CPB-related lung injury and affect the expression of AQP1 of lungs.Methods Twelve healthy dogs were divided into control group （C group） and ischemia postconditioning group （IPO group）.CPB procedures were implemented.Ten minutes later,the left pulmonary artery was separated and blocked.Postconditioning consisted of two cycles of 5-minute pulmonary artery reperfusion/5-minute reocclusion starting at the beginning of reperfusion.The 2×4 cm tissues of both sides of pulmonary apex,superior,middle and inferior lobe were taken before CPB （T1）,before occlusion and reopening of left pulmonary artery （T2,T3）,and 2 hours after CPB （T4）.Samples were used to evaluate lung injury degrees and to detect the expression of AQP1.At T1 and T4,blood was collected from femoral artery to calculate pulmonary function.Results At T4,each pulmonary function showed significant deterioration compared with T1.Lung injury could be found at the onset of CPB.However,the expression of AQP1 decreased and wet to dry weight ratio （W/D） increased after T2.In the left lung of C group,the worst pulmonary function and structures were detected.The slightest changes were discovered in the right lung of C group.A close relationship between W/D and lung injury score was found.The lung injury score was negatively related with the expression of AQP1.It was found that the expression of AQP1 was negatively connected with W/D.Conclusions In dog CPB models,lung injury induced by CPB was related with down regulated expression of AQP1.AQP1 is believed to be involved in the mechanisms of lung ischemia/reperfusion （I/R） injury caused by CPB.IPO increases the expression of AQP1,provides a protective effect on lung suffering from CPB,and alleviates CPB-related lung injury.展开更多
Background Cardiopulmonary bypass （CPB） has been shown to be associated with a systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protecti...Background Cardiopulmonary bypass （CPB） has been shown to be associated with a systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a good rat model of CPB to study the pathophysiology of potential complications. Methods Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into a CPB group （n=10） and a control group （n=10）. All rats were anaesthetized and mechanically ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular and transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery. Priming consisted of 8 ml of homologous blood and 8 ml of colloid. The surface of the hollow fiber oxygenator was 0.075 m~. CPB was conducted for 60 minutes at a flow rate of 100-120 ml. kg-1. min-1 in the CPB group. Oxygen flow/perfusion flow was 0.8 to 1.0, and the mean arterial pressure remained 60-80 mmHg. Blood gas analysis, hemodynamic investigations, and lung histology were subsequently examined. Results All CPB rats recovered from the operative process without incident. Normal cardiac function after successful weaning was confirmed by electrocardiography and blood pressure measurements. Mean arterial pressure remained stable. The results of blood gas analysis at different times were within the normal range. Levels of IL-113 and TNF-a were higher in the lung tissue in the CPB group （P 〈0.005）. Histological examination revealed marked increases in interstitialcongestion, edema, and inflammation in the CPB group. Conclusion This novel, recovery, and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.展开更多
Importance:Dexmedetomidine inhibits the inflammatory response associated with cardiopulmonary bypass(CPB)and protects neural function.However,the mechanism of dexmedetomidine’s anti-inflammatory pathway is unclear.Ob...Importance:Dexmedetomidine inhibits the inflammatory response associated with cardiopulmonary bypass(CPB)and protects neural function.However,the mechanism of dexmedetomidine’s anti-inflammatory pathway is unclear.Objective:To investigate the effect of dexmedetomidine on the cognitive level and expression of inflammatory factors in children with congenital heart disease undergoing intraoperative CPB.Methods:Ninety children with congenital heart disease were recruited and randomly divided into 3 groups of 30 children in each.In Group 1,a 1.0μg·kg-1·h-1 intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia,followed by a 0.2μg·kg-1·h-1 infusion until the surgical incision.In Group 2,a 0.5μg/kg intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia,followed by a 0.1μg·kg-1·h-1 infusion until the surgical incision.The control group was given physiological saline using the same method as in Groups 1 and 2.The serum levels of nuclear factor-kappa B(NF-κB),S-100βprotein,neuron-specific enolase(NSE),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were measured before the surgery(T1),at the end of CPB(T2),2 hours after CPB(T3),6 hours after CPB(T4),and 24 hours after CPB(T5).The Wechsler Intelligence Scale for children(WISC)was measured before the operation and at 3,6,and 12 months after the operation to evaluate the neurodevelopmental state of the children.Results:The levels of the NF-κB,S-100βprotein,NSE,TNF-α,IL-6 were significantly higher at T2,T3,or T4 than before the surgery(T1)in the control group or the dexmedetomidine groups.However,the increases of NF-κB,TNF-α,IL-6,S-100βand NSE levels were significantly smaller in the dexmedetomidine groups than those in the control group(P<0.017).The WISC scores were similar among the three groups before or after the operation.Interpretation:The increases in NF-κB,TNF-α,and IL-6 levels indicated aggravation of the inflammatory reaction and the increase S-100βprotein and NSE levels indicated that the nervous system was damaged.Administration of dexmedetomidine to children with congenital heart disease undergoing intraoperative CPB can inhibit the inflammatory response and may ameliorate the neurodevelopmental damage caused by CPB.展开更多
Background:This study evaluated differential inflammatory response to cardiopulmonary bypass reoxygenation in tetralogy of Fallot repair.Methods:We performed a retrospective study at a cardiovascular center from 2012 ...Background:This study evaluated differential inflammatory response to cardiopulmonary bypass reoxygenation in tetralogy of Fallot repair.Methods:We performed a retrospective study at a cardiovascular center from 2012 to 2018,including 500 patients aged 1 week–18 years who received complete repair of tetralogy of Fallot.Patients were grouped according to tertiles of preoperative RVOT gradient on echocardiography into mild,moderate,and severe stenosis.We measured the highest perfusate oxygenation(PpO_(2))during aortic occlusion as independent variable.Primary outcome was systemic inflammatory response syndrome(SIRS)within 7 days postoperatively or the time of death or discharge.Results:Overall,rate of SIRS was 24.2% without significant differences among three groups(P>0.05).Older age,male,and smaller indexed left ventricular end-diastolic volume is independent risk factor of SIRS.There were significant interactions between RVOT stenosis and PpO2 on SIRS(P interaction=0.011):higher PpO_(2) was associated with a greater SIRS risk among combined moderate and severe stenotic children(OR 1.46395%CI[1.080,1.981]per-SD increase,P=0.014)but not among mild stenotic children(OR 0.900[0.608,1.333]per-SD increase;P=0.600),independent of covariates.Conclusion:The association of PpO_(2) with SIRS was modified by RVOT obstruction severity in tetralogy of Fallot repair.展开更多
Background: Acute kidney injury (AKI) is a severe common postoperative complication of cardiac surgery (CS). It increases the risk of mortality by up to 80%. Therefore, it is essential to have preoperative risk evalua...Background: Acute kidney injury (AKI) is a severe common postoperative complication of cardiac surgery (CS). It increases the risk of mortality by up to 80%. Therefore, it is essential to have preoperative risk evaluation tools. Frailty is a marker of deterioration of physiologic systems and may be associated with AKI. Purpose: The study aimed to determine the utility of frailty as a predictor of AKI after CS. Method: We enrolled 91 patients undergoing CS with cardiopulmonary bypass to determine if they had frailty before surgery and were associated with postoperative AKI. The diagnosis of postoperative AKI was based on the serum creatinine criteria of the Acute Kidney Injury Network classification up to 7 days following CS. Results: The incidence of postoperative AKI was 62% in the frail group and 21% in the non-frail group. Frailty was associated with a higher risk of AKI (relative risk [RR] = 3.00, 95% CI 1.56 - 5.77, p = 0.00). In regression models, there were associations between frailty and postoperative AKI. Conclusion: This study demonstrated that frailty could be a predictor for post-CS AKI. Therefore, frailty assessment should become an essential part of the preoperative evaluation to help the anesthesiologist to estimate the surgical risk and develop preoperative and transoperative strategies to preserve the renal function and improve the cardiac surgery outcome.展开更多
Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury(ALI), including acute respiratory distress syndrome(ARDS), in patients after cardiac surgery. We previously foun...Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury(ALI), including acute respiratory distress syndrome(ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles(eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of e EVs after cardiopulmonary bypass, remains unclear. Plasma plasminogenactivated inhibitor-1(PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice(C57BL/6,Toll-like receptor 4 knockout(TLR4^(-/-))) and inducible nitric oxide synthase knockout(iNOS^(-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3(JAK2/3)-signal transducer and activator of transcription 3(STAT3)-interferon regulatory factor 1(IRF-1)pathway, along with i NOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors(AG490 or S3I-201, respectively), and was relieved in TLR4-/-and iNOS-/-mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1(FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.展开更多
Objective： To evaluate the efficacy of Xuebijing Injection（血必净注射液, XBJ） on the lung injury induced by cardiopulmonary bypass（CPB）. Methods： Fifty patients undergoing CPB were randomized to either the salin...Objective： To evaluate the efficacy of Xuebijing Injection（血必净注射液, XBJ） on the lung injury induced by cardiopulmonary bypass（CPB）. Methods： Fifty patients undergoing CPB were randomized to either the saline group or XBJ group according to a random number table（25 cases in each group）. The patients in the saline group received saline and patients in XBJ group received XBJ at 12 h prior to the operation, at the beginning of the operation, and at 12 h after the second injection. The PaO_2/Fi O2 at extubation 3 days post-operation, duration of ventilation in the intensive care unit（ICU）, and lengths of stay in the ICU and hospital were recorded. The levels of inflammatory mediators including interleukin（IL）-1β, IL-8, IL-10, and C-reactive protein（CRP） in bronchoalveolar lavage fluid（BALF） and plasma were measured. The neutrophil count and elastase neutrophil elastase in BALF were also measured. In addition, adverse events were monitored. Results： The PaO-2/FiO_2 in the XBJ group was higher than that in the saline group from 12 to 72 h post-operation（all P〈0.05）. The blood levels of IL-1β, IL-8, and CRP in the XBJ group from 12 to 72 h were all significantly lower than those in the saline group（all P〈0.05）. In contrast, the level of the anti-inflammatory cytokine IL-10 was significantly higher in the XBJ group than in the saline group（P〈0.05）. In addition, 4 patients presented with atelectasis in the saline group and none in the XBJ group. Ten patients experienced mild acute respiratory distress syndrome（ARDS） during hospitalization, and 5 patients with mild ARDS were in the XBJ group（P〈0.05）. Conclusion： XBJ shows protective potential against lung injury in patients who undergo CPB surgery, possibly through the downregulation of inflammatory mediators, reduction in neutrophil infiltration, and upregulation of IL-10（Trial registry： Chi CTR-TRC-14004628）.展开更多
Background Pulmonary artery perfusion during cardiopulmonary bypass （CPB） is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the pro...Background Pulmonary artery perfusion during cardiopulmonary bypass （CPB） is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension. Methods Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group （n=12） and control group （n=-12）. Oxygen index, alveolar-arterial 02 gradient, serum levels of malondialchehyche （MDA）, interleukin （IL）-6, -8, -10, soluble intercellular adhesion molecule-1 （slCAM-1）, and P-seiectin were measured before commencement and serially for 48 hours after termination of bypass. Results Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB, but it was restored faster and earlier in the perfused group. The serum levels of IL-8, slCAMol, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for slCAM-1 The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time. Conclusion In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response.展开更多
文摘Although the lung injury caused by cardiopulmonary bypass(CPB)has been extensively investigated,the incidence and mortality of lung injury after CPB remain a prominent clinical problem.The poor outcome has been attributed to multifactorial etiology,including the systemic inflammatory response and ischemia reperfusion(I/R)injury during CPB.Lung injury after CPB is a complex pathophysiological process and has many clinical manifestations of mild to severe disease.Which is associated with prognosis.To alleviate this lung injury,interventions that address the pathogenesis are particularly important.This review summarizes the pathogenesis,mechanism and treatment options of lung injury after CPB,such as lung protection with intralipid.
基金Supported by Military Medical and Sanitation ResearchFund (01Z074)
文摘Objective： To explore the role of polymorphonuclear neutrophils （PMN） activation in lung injury following cardiopulmonary bypass （CPB）. Methods： Twenty four cases of patients with rheumatic heart disease were enrolled in this study to detect the situation of PMN activation and the degree of lung injury. Bronchoalveolar lavage fluid （BALF） and blood samples were collected just after anaesthesia and 4 h postoperatively. Related clinic data were recorded. Results： This cohort included 4 male and 20 female with age ranging from 29 to 69 years old, and body mass from 37 to 73 kg. Mean cardiopulmonary bypass time was （106.46±33.58） rain, mean cross clamp time was （77.58_＋28.02） rain, and mean mechanical ventilation time was （24.17±30.90） h. Postoperative PaO2/FiO2 decreased significantly than that during preoperation （P=0.000）. The postoperative WBC counts in peripheral blood and in BALF were both increased significantly than those during preoperation. And the postoperative rates of PMN in BALF were also increased significantly. Postoperative neutriphil elastase （NE） and myeloperoxidase （MPO） released from inflammatory ceils were increased significantly （P=0.000） both in plasma and BALF. The postoperative yon Willebrand factor （vWF） concentration in plasma was also increased significantly （P=0.000）. The postoperative concentration of sLPI in plasma was decreased, whereas it was increased significantly in BALF. Furthermore, there was a negative correlation between NE and PaO2/FiO2 both in BALF and in plasma. A negative correlation was present between vWF in plasma and PaO2/FiO2. A positive correlation was found between sLPI in plasma and PaO2/FiO2. Conclusion： PMN is recruited and activated after CPB and released large quantity of proteases, and lead to lung injury, sLPI is an important protective factor against inflammatory injury.
基金Supported by grants from National Natural Science Foundation of China (30170929).
文摘Objective To study if using autologous lung as a substitute of oxygenator in cardiopulmonary bypass is better than the conventional cardiopulmonary bypass with artificial oxygenator in pulmonary preservation. Methods Twelve piglets were randomly divided into two groups （ n = 6）. The isolated lung perfusion model was established. The experimental animals underwent continuous lung perfusion for about 120 rain. While the control animals underwent 90 rain lung ischemia followed by 30 rain reperfusion. Another 12 piglets were randomly divided into two groups （ n =6）. The experimental animals underwent bi-ventricular bypass with autologous lung perfusion. While control animals underwent conventional cardiopulmonary bypass with artificial oxygenator. The bypass time and aortic cross clamping time were 135 rain and 60 rain respectively for each animal. The lung static compliance （Cstat）, alveolus-artery oxygen difference （PA-aO2 ） , TNF-α, IL-6 and wet to dry lung weight ratio （W/D） were measured. Histological and ultra-structural changes of the lung were also observed after bypass. Results After either isolated lung perfusion or cardiopulmonary bypass, the Cstat decreased, the PA-aO2 increased and the content of TNF-α increased for both groups, but the changes of experimental group were much less than those of control group. The lower W/D ratio and mild pathological changes in experimental group than those in control group were also demonstrated. Conclusion Autologous lung is able to tolerate the nonpulsatile perfusion. It can be used as a substitute to artificial ogygenator in cardiopulmonary bypass to minimize the inflammatory pulmonary injury caused mainly by ischemic reperfusion and interaction of the blood to the non-physiological surface of artificial oxygenator.
文摘Objective To testify the lung injury induced by cardiopulmonary bypass(CPB) in canine model and observe the influence of CPB on the aquaporin 1 (AQP1) mRNA expression in canine lung. Methods 8 mongrel dogs were used to perform the cardiopulmonary bypass. The hearts arrested for 90 minutes with mild hypothermia and rebeated for 6 hours. The hemodynamics,the ratio of lung dry weight and wet weight,the plasmic
文摘Acute kidney injury (AKI) is defined by 0.3 mg/dL increase in serum creatinine (SCr) and is associated with higher incidence of postoperative mortality after coronary artery bypass graft (CABG). There are few clinical studies on the effect of dexmedetomidine (DEX) on renal function. We evaluated AKI after coronary artery bypass graft with and without cardiopulmonary bypass (CPB) under anesthesia with DEX. Method: In this retrospective study, we performed serial analysis of serum creatinine (SCr) up to 48 hours after surgery in 286 patients who underwent CABG. We tested the similarities between groups, evaluating patients separately for use of CPB and DEX. Each patient was evaluated for his or her SCr at the following points in time: preoperative, immediately postoperative, 24 hours postoperative, and 48 hours postoperative. Preoperative SCr was used as the baseline value for each patient. If the SCr increased ≥0.3 mg/dL in at least one of the periods, the patient was classified as having AKI. We also assessed the risk for AKI in patients with altered preoperative SCr (values between 1.1 to 2.0 mg/dL for women or 1.3 to 2.0 mg/dL for men) compared to patients with normal SCr. Results: The groups were similar for preoperative weight, age, and altered SCr. Patients were anesthetized with DEX and who underwent CPB exhibited higher incidence of AKI (p = 0.043). Without CPB, there was higher incidence of AKI after using DEX (p = 0.066). Conclusion: Anaesthesia with DEX increased the incidence of AKI after myocardial revascularization surgery in patients who underwent CPB.
文摘Acute respiratory failure after surgery for aortic dissection is a serious complication that has been associated with increased mortality and morbidity. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is reported as one of the treatments for this life-threatening complication. A 78-year-old male patient was admitted to our hospital for Stanford type A acute aortic dissection. He underwent emergency replacement of the ascending aorta, after which he developed acute lung injury. It was difficult to maintain oxygenation with a respirator mask. Therefore, VV-ECMO was initiated on postoperative day 1. The oxygenation gradually improved, and VV-ECMO was continued until postoperative day 13. On postoperative day 25, mechanical ventilation was withdrawn. The patient was discharged from the hospital on postoperative day 149. We report a case of successful treatment of acute lung injury with VV-ECMO initiated after surgery for aortic dissection. VV-ECMO can be considered as a treatment option for severe acute lung injury after surgery for aortic dissection.
文摘Background It has found that ischemic postconditioning （IPO） might decrease pulmonary ischemia/reperfusion （I/ R） injury,which is one of the main reasons of lung injury caused by cardiopulmonary bypass （CPB）.It was found that aquaporins （AQPs） play a role in the maintenance of fluid homeostasis.But it is still unclear whether IPO influences the expression of aquaporin-1 （AQP1）.This study was designed to investigate whether IPO can reduce CPB-related lung injury and affect the expression of AQP1 of lungs.Methods Twelve healthy dogs were divided into control group （C group） and ischemia postconditioning group （IPO group）.CPB procedures were implemented.Ten minutes later,the left pulmonary artery was separated and blocked.Postconditioning consisted of two cycles of 5-minute pulmonary artery reperfusion/5-minute reocclusion starting at the beginning of reperfusion.The 2×4 cm tissues of both sides of pulmonary apex,superior,middle and inferior lobe were taken before CPB （T1）,before occlusion and reopening of left pulmonary artery （T2,T3）,and 2 hours after CPB （T4）.Samples were used to evaluate lung injury degrees and to detect the expression of AQP1.At T1 and T4,blood was collected from femoral artery to calculate pulmonary function.Results At T4,each pulmonary function showed significant deterioration compared with T1.Lung injury could be found at the onset of CPB.However,the expression of AQP1 decreased and wet to dry weight ratio （W/D） increased after T2.In the left lung of C group,the worst pulmonary function and structures were detected.The slightest changes were discovered in the right lung of C group.A close relationship between W/D and lung injury score was found.The lung injury score was negatively related with the expression of AQP1.It was found that the expression of AQP1 was negatively connected with W/D.Conclusions In dog CPB models,lung injury induced by CPB was related with down regulated expression of AQP1.AQP1 is believed to be involved in the mechanisms of lung ischemia/reperfusion （I/R） injury caused by CPB.IPO increases the expression of AQP1,provides a protective effect on lung suffering from CPB,and alleviates CPB-related lung injury.
基金This study was supported by grants from the Capital Medical University-Clinical Research Cooperation Fund （No. l lJLS0, No. 13JL26）, the National Natural Science Foundation of China （No. 81371443, No. 81070055）, Beijing Natural Science Foundation （No. 7112046, No. 7122056）, Beijing Health System High Level Health Technical Personnel Training Plan （No. 2011-1-4）, and the Specialized Research Fund for the Doctoral Program of Higher Education （SRFDP, No. 20111107110006）.
文摘Background Cardiopulmonary bypass （CPB） has been shown to be associated with a systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a good rat model of CPB to study the pathophysiology of potential complications. Methods Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into a CPB group （n=10） and a control group （n=10）. All rats were anaesthetized and mechanically ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular and transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery. Priming consisted of 8 ml of homologous blood and 8 ml of colloid. The surface of the hollow fiber oxygenator was 0.075 m~. CPB was conducted for 60 minutes at a flow rate of 100-120 ml. kg-1. min-1 in the CPB group. Oxygen flow/perfusion flow was 0.8 to 1.0, and the mean arterial pressure remained 60-80 mmHg. Blood gas analysis, hemodynamic investigations, and lung histology were subsequently examined. Results All CPB rats recovered from the operative process without incident. Normal cardiac function after successful weaning was confirmed by electrocardiography and blood pressure measurements. Mean arterial pressure remained stable. The results of blood gas analysis at different times were within the normal range. Levels of IL-113 and TNF-a were higher in the lung tissue in the CPB group （P 〈0.005）. Histological examination revealed marked increases in interstitialcongestion, edema, and inflammation in the CPB group. Conclusion This novel, recovery, and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.
基金Scientific and Technological Projects of Henan Province,China(no.182102310440)Medical Science R&D Program of Henan Province,China(no.2018020598)International Research Laboratory Program of Henan Province,China(no.201605-005).
文摘Importance:Dexmedetomidine inhibits the inflammatory response associated with cardiopulmonary bypass(CPB)and protects neural function.However,the mechanism of dexmedetomidine’s anti-inflammatory pathway is unclear.Objective:To investigate the effect of dexmedetomidine on the cognitive level and expression of inflammatory factors in children with congenital heart disease undergoing intraoperative CPB.Methods:Ninety children with congenital heart disease were recruited and randomly divided into 3 groups of 30 children in each.In Group 1,a 1.0μg·kg-1·h-1 intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia,followed by a 0.2μg·kg-1·h-1 infusion until the surgical incision.In Group 2,a 0.5μg/kg intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia,followed by a 0.1μg·kg-1·h-1 infusion until the surgical incision.The control group was given physiological saline using the same method as in Groups 1 and 2.The serum levels of nuclear factor-kappa B(NF-κB),S-100βprotein,neuron-specific enolase(NSE),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were measured before the surgery(T1),at the end of CPB(T2),2 hours after CPB(T3),6 hours after CPB(T4),and 24 hours after CPB(T5).The Wechsler Intelligence Scale for children(WISC)was measured before the operation and at 3,6,and 12 months after the operation to evaluate the neurodevelopmental state of the children.Results:The levels of the NF-κB,S-100βprotein,NSE,TNF-α,IL-6 were significantly higher at T2,T3,or T4 than before the surgery(T1)in the control group or the dexmedetomidine groups.However,the increases of NF-κB,TNF-α,IL-6,S-100βand NSE levels were significantly smaller in the dexmedetomidine groups than those in the control group(P<0.017).The WISC scores were similar among the three groups before or after the operation.Interpretation:The increases in NF-κB,TNF-α,and IL-6 levels indicated aggravation of the inflammatory reaction and the increase S-100βprotein and NSE levels indicated that the nervous system was damaged.Administration of dexmedetomidine to children with congenital heart disease undergoing intraoperative CPB can inhibit the inflammatory response and may ameliorate the neurodevelopmental damage caused by CPB.
基金This work was supported by the National Natural Science Foundation of China(82000305,81974033)the National Natural Science Foundation of Jiangsu Province(BK20191069).
文摘Background:This study evaluated differential inflammatory response to cardiopulmonary bypass reoxygenation in tetralogy of Fallot repair.Methods:We performed a retrospective study at a cardiovascular center from 2012 to 2018,including 500 patients aged 1 week–18 years who received complete repair of tetralogy of Fallot.Patients were grouped according to tertiles of preoperative RVOT gradient on echocardiography into mild,moderate,and severe stenosis.We measured the highest perfusate oxygenation(PpO_(2))during aortic occlusion as independent variable.Primary outcome was systemic inflammatory response syndrome(SIRS)within 7 days postoperatively or the time of death or discharge.Results:Overall,rate of SIRS was 24.2% without significant differences among three groups(P>0.05).Older age,male,and smaller indexed left ventricular end-diastolic volume is independent risk factor of SIRS.There were significant interactions between RVOT stenosis and PpO2 on SIRS(P interaction=0.011):higher PpO_(2) was associated with a greater SIRS risk among combined moderate and severe stenotic children(OR 1.46395%CI[1.080,1.981]per-SD increase,P=0.014)but not among mild stenotic children(OR 0.900[0.608,1.333]per-SD increase;P=0.600),independent of covariates.Conclusion:The association of PpO_(2) with SIRS was modified by RVOT obstruction severity in tetralogy of Fallot repair.
文摘Background: Acute kidney injury (AKI) is a severe common postoperative complication of cardiac surgery (CS). It increases the risk of mortality by up to 80%. Therefore, it is essential to have preoperative risk evaluation tools. Frailty is a marker of deterioration of physiologic systems and may be associated with AKI. Purpose: The study aimed to determine the utility of frailty as a predictor of AKI after CS. Method: We enrolled 91 patients undergoing CS with cardiopulmonary bypass to determine if they had frailty before surgery and were associated with postoperative AKI. The diagnosis of postoperative AKI was based on the serum creatinine criteria of the Acute Kidney Injury Network classification up to 7 days following CS. Results: The incidence of postoperative AKI was 62% in the frail group and 21% in the non-frail group. Frailty was associated with a higher risk of AKI (relative risk [RR] = 3.00, 95% CI 1.56 - 5.77, p = 0.00). In regression models, there were associations between frailty and postoperative AKI. Conclusion: This study demonstrated that frailty could be a predictor for post-CS AKI. Therefore, frailty assessment should become an essential part of the preoperative evaluation to help the anesthesiologist to estimate the surgical risk and develop preoperative and transoperative strategies to preserve the renal function and improve the cardiac surgery outcome.
基金supported by the National Key Research and Development Program of China(2021YFA0805100)the National Natural Science Foundation of China(81830013,81770241,81970363,82000362,92268202,81170271,81370370,81490531,81670392,81600382)+6 种基金the National Natural Science Foundation of China Distinguished Young Scholar Grant(81325001)“973 Project”from the Ministry of Science and Technology of China(2009CB522104)Guangdong Basic and Applied Basic Research Foundation,China(2019B1515120092)the Science and Technology Planning Project of Guangzhou,China(202103000016)the Changjiang Scholars Program from the Ministry of Education of Chinathe Sun Yat-sen University Clinical Research 5010 Programthe Program of National Key Clinical Specialties。
文摘Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury(ALI), including acute respiratory distress syndrome(ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles(eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of e EVs after cardiopulmonary bypass, remains unclear. Plasma plasminogenactivated inhibitor-1(PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice(C57BL/6,Toll-like receptor 4 knockout(TLR4^(-/-))) and inducible nitric oxide synthase knockout(iNOS^(-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3(JAK2/3)-signal transducer and activator of transcription 3(STAT3)-interferon regulatory factor 1(IRF-1)pathway, along with i NOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors(AG490 or S3I-201, respectively), and was relieved in TLR4-/-and iNOS-/-mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1(FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.
文摘Objective： To evaluate the efficacy of Xuebijing Injection（血必净注射液, XBJ） on the lung injury induced by cardiopulmonary bypass（CPB）. Methods： Fifty patients undergoing CPB were randomized to either the saline group or XBJ group according to a random number table（25 cases in each group）. The patients in the saline group received saline and patients in XBJ group received XBJ at 12 h prior to the operation, at the beginning of the operation, and at 12 h after the second injection. The PaO_2/Fi O2 at extubation 3 days post-operation, duration of ventilation in the intensive care unit（ICU）, and lengths of stay in the ICU and hospital were recorded. The levels of inflammatory mediators including interleukin（IL）-1β, IL-8, IL-10, and C-reactive protein（CRP） in bronchoalveolar lavage fluid（BALF） and plasma were measured. The neutrophil count and elastase neutrophil elastase in BALF were also measured. In addition, adverse events were monitored. Results： The PaO-2/FiO_2 in the XBJ group was higher than that in the saline group from 12 to 72 h post-operation（all P〈0.05）. The blood levels of IL-1β, IL-8, and CRP in the XBJ group from 12 to 72 h were all significantly lower than those in the saline group（all P〈0.05）. In contrast, the level of the anti-inflammatory cytokine IL-10 was significantly higher in the XBJ group than in the saline group（P〈0.05）. In addition, 4 patients presented with atelectasis in the saline group and none in the XBJ group. Ten patients experienced mild acute respiratory distress syndrome（ARDS） during hospitalization, and 5 patients with mild ARDS were in the XBJ group（P〈0.05）. Conclusion： XBJ shows protective potential against lung injury in patients who undergo CPB surgery, possibly through the downregulation of inflammatory mediators, reduction in neutrophil infiltration, and upregulation of IL-10（Trial registry： Chi CTR-TRC-14004628）.
文摘Background Pulmonary artery perfusion during cardiopulmonary bypass （CPB） is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension. Methods Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group （n=12） and control group （n=-12）. Oxygen index, alveolar-arterial 02 gradient, serum levels of malondialchehyche （MDA）, interleukin （IL）-6, -8, -10, soluble intercellular adhesion molecule-1 （slCAM-1）, and P-seiectin were measured before commencement and serially for 48 hours after termination of bypass. Results Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB, but it was restored faster and earlier in the perfused group. The serum levels of IL-8, slCAMol, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for slCAM-1 The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time. Conclusion In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response.
