Brain injury following cardiac arrest (CA) is a significant cause of mortality and poor prognosis in patients, and effective treatment strategies remain limited. Stem cell-derived extracellular vesicles (EVs), a novel cell-free therapeutic approach, have recently demonstrated significant potential in the field of brain injury repair. EVs, key mediators of stem cell paracrine and autocrine signaling, are enriched with bioactive molecules such as non-coding RNAs and proteins. These EVs have the capacity to traverse the bloodstream, reach injury sites, and modulate various biological processes, including neuronal survival, oxidative stress, inflammatory responses, blood-brain barrier integrity, and neurovascular regeneration.This review aims to provide a comprehensive overview of the research history, structural characteristics, and in vivo distribution and metabolism of stem cell-derived EVs. The review further explores their therapeutic potential and underlying mechanisms in post-CA brain injury, including the inhibition of neuronal apoptosis, alleviation of oxidative stress and inflammation, promotion of blood-brain barrier repair, and enhancement of neurovascular regeneration. Additionally, the review highlights emerging directions and challenges in the clinical application of stem cell-derived EVs, offering theoretical insights and perspectives for future research and translational development. The potential of stem cell-derived EVs as a breakthrough strategy for treating post-CA brain injury is underscored, offering renewed optimism for enhancing patient outcomes.
OBJECTIVE:Comparing the effects of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on outcomes in patients with in-hospital cardiac arrest (IHCA) in China. The benefits of ECPR over CCPR in patients with IHCA remain controversial. DESIGN:This article analyzed data from the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA) study, which consecutively enrolled patients with IHCA from July 1, 2019, to December 31, 2020. Patients who received ECPR were selected as the case group and matched with patients who received CCPR as the control group by propensity score at a ratio of 1:4. A parallel questionnaire survey of participating hospitals was conducted, to collect data on ECPR cases from January 1, 2021 to November 30, 2021. The primary outcome was survival to discharge or 30-day survival. SETTING:We included 39 hospitals across 31 provinces in China. PATIENTS:Patients receiving cardiopulmonary resuscitation and without contraindications to ECPR were selected from the BASIC-IHCA database. Patients older than 75 years, not witnessed, or with cardiopulmonary resuscitation duration less than 10 min were excluded. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:A total of 4853 patients met the inclusion criteria before matching, with 34 undergoing ECPR (median age, 56.5 yr; 67.65% male) and 4819 underwent CCPR (median age, 59 yr; 64.52% male). There were 132 patients receiving CCPR and 33 patients receiving ECPR who were eventually matched. The ECPR group had significantly higher survival rates at discharge or 30-day survival (21.21% vs. 7.58%, p = 0.048). The ECPR group had significantly lower mortality rates (hazard ratio 0.57; 95% CI, 0.38-0.91) than the CCPR group at discharge or 30 days. Besides the BASIC-IHCA study, the volume of ECPR implementations and the survival rate of patients with ECPR (29.4% vs. 10.4%. p = 0.004) in participating hospitals significantly improved. CONCLUSIONS:ECPR may be beneficial compared with CCPR for patient survival after IHCA and should be considered for eligible patients with IHCA.
Thrombosis and plasma leakage are two of the most frequent dysfunctions of polypropylene (PP) hollow fiber membrane (PPM) used in extracorporeal membrane oxygenation (ECMO) therapy. In this study, a superhydrophilic endothelial membrane mimetic coating (SEMMC) was constructed on polydopamine-polyethyleneimine pre-coated surfaces of the PPM oxygenator and its ECMO circuit to explore safer and more sustainable ECMO strategy. The SEMMC is fabricated by multi-point anchoring of a phosphorylcholine and carboxyl side chained copolymer (PMPCC) and grafting of heparin (Hep) to form PMPCC-Hep interface, which endows the membrane superior hemocompatibility and anticoagulation performances. Furthermore, the modified PPM reduces protein adsorption amount to less than 30 ng/cm2. More significantly, the PMPCC-Hep coated ECMO system extends the anti-leakage and non-clotting oxygenation period to more than 15 h in anticoagulant-free animal extracorporeal circulation, much better than the bare and conventional Hep coated ECMO systems with severe clots and plasma leakage in 4 h and 8 h, respectively. This SEMMC strategy of grafting bioactive heparin onto bioinert zwitterionic copolymer interface has great potential in developing safer and longer anticoagulant-free ECMO systems. Statement of significance A superhydrophilic endothelial membrane mimetic coating was constructed on surfaces of polypropylene hollow fiber membrane (PPM) oxygenator and its ECMO circuit by multi-point anchoring of a phosphorylcholine and carboxyl side chain copolymer (PMPCC) and grafting of heparin (Hep). The strong antifouling nature of the PMPCC-Hep coating resists the adsorption of plasma bio-molecules, resulting in enhanced hemocompatibility and anti-leakage ability. The grafted heparin on the zwitterionic PMPCC interface exhibits superior anticoagulation property. More significantly, the PMPCC-Hep coating achieves an extracorporeal circulation in a pig model for at least 15 h without any systemic anticoagulant. This endothelial membrane mimetic anticoagulation strategy shows great potential for the development of safer and longer anticoagulant-free ECMO systems.
目的 基于动物实验,探讨青蒿素(artesunate,Art)对心肺复苏(cardiopulmonary resuscitation,CPR)后肺组织是否具有保护作用及可能的机制.方法 将24头健康雄性大白猪随机分为假手术组(n=6)、CPR组(n=10)和Art组(n=8).其中CPR组和Art组采用室颤法制备CPR模型,假手术组仅进行外科准备.恢复自主循环后,Art组经股静脉持续泵入Art 4.8 mg/kg,维持2 h;CPR与假手术组同样方法泵入等量溶媒.比较3组动物基线(造模前)及复苏后肺损伤指标与肺损伤病理评分、肺组织炎症及高迁移率族蛋白B1(high mobility group box 1,HMGB1)/Toll样受体4(Toll-like receptor 4,TLR4)/核因子-κB(nuclear factor-κB,NF-κB)炎症通路活性变化.结果(1)肺损伤指标:3组基线血管外肺水指数(extravascular lung water index,ELWI)、肺血管通透性指数(pulmonary vascular permeability index,PVPI)和氧合指数(oxygenation index,OI)差异均无统计学意义(P均>0.05).相较于假手术组,CPR组复苏后 1h、2h和 4h时ELWI和PVPI均升高,复苏后1h、2h时OI均降低(P均<0.05);相较于CPR组,Art组复苏后不同时间点ELWI、PVPI和OI均所有改善,但仅复苏后 2h、4h时ELWI、PVPI有显著差异(P均<0.05).(2)肺损伤病理评分:相较于假手术组,CPR组、Art组复苏后24h时肺损伤病理评分均显著升高(P均<0.05);相较于CPR组,Art组复苏后24h时肺损伤病理评分降低(P<0.05).(3)肺组织炎症:相较于假手术组,CPR组、Art组复苏后 24h时肺组织肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1β和IL-6 水平均显著升高(P均<0.05);相较于CPR组,Art组复苏后24h时肺组织TNF-α、IL-1β和IL-6水平均降低(P均<0.05).(4)HMGB1/TLR4/NF-κB炎症通路活性:相较于假手术组,CPR组、Art组复苏后24h时肺组织HMGB1、TLR4 和NF-κB p65 蛋白水平均显著升高(P均<0.05);相较于CPR组,Art组复苏后24h时肺组织HMGB1、TLR4和NF-κB p65蛋白水平均降低(P均<0.05).结论 Art可减轻心脏骤停复苏后肺组织炎性损伤,其作用机制可能与抑制HMGB1/TLR4/NF-κB炎症信号通路活性有关.
Objective:To explore the protective effect and mechanism of sodium butyrate on cardio-brain injury after cardiopulmonary resuscitation in pigs.Methods:A total of 24 large white healthy male pigs were divided into a sham operation group (n = 6), a cardiopulmonary resuscitation group (n = 10) and a sodium butyrate group (n = 8) by a random number method. In the sham operation group, only tracheal intubation and arteriovenous catheterization were performed, and induced ventricular fibrillation and cardiopulmonary resuscitation were not performed. Cardiac arrest and cardiopulmonary resuscitation models were prepared by electrical stimulation for 9 min and cardiopulmonary resuscitation for 6 min. At 5 min after successful resuscitation, the sodium butyrate group was injected 75 mg/kg of sodium butyrate through the femoral vein for 1 h. Sham operation and cardiopulmonary resuscitation groups were given the same amount of isotonic NaCl solution by the same method. Serum levels of cardiac troponin I (cTnI), creatine kinase MB (CK-MB), neuron specific enolase (NSE) and S100 calcium-binding protein B (S100B) were measured by the enzyme-linked immunosorbent assay (ELISA) before cardiac arrest and at 1, 2, 4, and 24 h after resuscitation. At 24 h after resuscitation, the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and ubiquitin-binding protein 62 (p62) in the cardiac muscle and cerebral cortex tissue were detected by western-blotting, and the apoptosis rate was detected by the TUNEL method.Results:In the cardiopulmonary resuscitation group, nine pigs were successfully resuscitated, seven of which survived to 24 h. In the sodium butyrate group, seven pigs were resuscitated successfully, and all survived to 24 h. There was no significant difference in the success of 24-h resuscitation among the three groups (χ2 = 3.381, P = 0.184). At 1, 2, 4 and 24 h after resuscitation, serum cTnI (F = 62.736, 201.265, 330.083, 643.538; all P < 0.001), CK-MB (F = 90.380, 181.548, 669.657, 707.485; all P < 0.001), NSE (F = 92.302, 125.730, 590.627, 1 130.372; all P < 0.001) and S100B (F = 42.831, 152.004, 295.517, 1 023.409; all P < 0.001) were observed and compared in the three groups, and the differences were statistically significant. Compared with the sham operation group, the cTnI, CK-MB, NSE and S100B levels in serum were significantly increased at 2, 4 and 24 h after resuscitation in the cardiopulmonary resuscitation group and sodium butyrate group, which were highest in the cardiopulmonary resuscitation group (all P < 0.05). At 24 h after resuscitation, the levels of autophagy markers LC3 (F = 81.671, 49.204; both P < 0.001) and p62 (F = 127.620, 65.594; both P < 0.001) and the apoptosis rate (F = 116.750, 249.105; both P < 0.001) in cardiomyocytes and cerebral cortex cells were observed and compared in the three groups, and the differences were statistically significant. Compared with the sham operation group, the LC3 expression and apoptosis index were increased, and the p62 expression was decreased in myocardium and cerebral cortex of pigs in the cardiopulmonary resuscitation group and sodium butyrate group at 24 h after resuscitation (all P < 0.05). However, compared with the cardiopulmonary resuscitation group, the LC3 expression and apoptosis index were decreased, and the p62 expression was increased in the myocardium and cerebral cortex in the sodium butyrate group at 24 h after resuscitation (all P < 0.05).Conclusion:Sodium butyrate has a protective effect on cardio-brain injury after resuscitation of cardiac arrest, and the mechanism may be related to inhibition of autophagy and apoptosis.
Objective:To investigate the effect of sodium butyrate (NaB) on renal and intestinal injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) and its related mechanism.Methods:Twenty-four domestic healthy male swines were randomly divided into 3 groups: sham group ( n=6), CA-CPR group ( n=10) and NaB group ( n=8). The animals only underwent operational preparation in the sham group. The animal model of CA and CPR was established by 9 min of ventricular fibrillation induced by electrical stimulation in the ventricle and then 6 min of CPR in the CA-CPR and NaB groups. At 5 min after resuscitation, a dose of 75 mg/kg of NaB was intravenously infused for 1 h in the NaB group, and meanwhile the same volume of vehicle was intravenously infused in the sham and CA-CPR groups. At 1, 2, 4, and 24 h after resuscitation, blood samples were collected to detect the renal and intestinal injury biomarkers, such as creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP), and diamine oxidase (DAO). At 24 h after resuscitation, renal and intestinal tissue specimens were harvested to detect the protein markers of cell autophagy including microtubule-associated protein light chain 3 Ⅱ (LC3Ⅱ) and p62 expression, and also renal and intestinal apoptosis. Statistical analysis was performed by SPSS software, and continuous variables were compared with one-way analysis of variance among the groups. Results:After CA-CPR, the renal and intestinal injury biomarkers including Cr, BUN, IFABP, and DAO were significantly increased at all time points after resuscitation in the CA-CPR and NaB groups compared with the sham group (all P<0.05). The injury biomarkers mentioned-above were significantly lower at all time points after resuscitation in the NaB group than in the CA-CPR group [Cr (μmol/L): (90±5) vs. (127±9) at 1 h, (135±14) vs. (168±9) at 2 h, (174±10) vs. (211±12) at 4 h, (192±10) vs. (253±13) at 24 h; BUN (mmol/L): (10.5±1.0) vs. (12.3±1.0) at 1 h, (12.2±1.2) vs. (15.3±0.9) at 2 h, (13.6±1.3) vs. (18.3±1.2) at 4 h, (15.4±1.4) vs. (21.5±1.4) at 24 h; IFABP (pg/mL): (502±33) vs. (554±32) at 1 h, (574±52) vs. (644±41) at 2 h, (646±44) vs. (732±43) at 4 h, (711±42) vs. (828±42) at 24 h; DAO (U/mL): (8.6±1.0) vs. (10.5±0.9) at 1 h, (10.6±1.2) vs. (12.8±1.0) at 2 h, (12.1±1.0) vs. (15.0±1.0) at 4 h, (14.1±1.1) vs. (17.6±1.0) at 24 h, (all P<0.05)]. Renal and intestinal tissue detection indicated that cell autophagy and apoptosis were significantly increased after resuscitation in the CA-CPR and NaB groups compared with the sham group, which was indicated by significantly increased LC3Ⅱ and decreased p62 expression, and markedly elevated apoptosis index (all P<0.05). However, cell autophagy and apoptosis in the kidney and intestine were significantly milder after resuscitation in the NaB group than in the CA-CPR group [renal LC3 Ⅱ: (1.15±0.17) vs. (2.23±0.31), p62: (1.60±0.10) vs. (1.17±0.08), apoptosis index (%): (21.2±5.3) vs. (50.9±7.9); intestinal LC3 Ⅱ: (1.03±0.17) vs. (1.71±0.21), p62: (1.30±0.29) vs. (0.79±0.29), apoptosis index (%): (25.6±6.1) vs. (61.7±10.7), all P<0.05]. Conclusions:NaB could alleviate the severity of renal and intestinal damage after CA-CPR in swine, and its protective mechanism may be related to the inhibition of cell autophagy and apoptosis.
Extracorporeal cardiopulmonary resuscitation (ECPR) refers to the use of extracorporeal membrane oxygenation (ECMO) to ensure the perfusion of important organs after the traditional cardiopulmonary resuscitation (CCPR) has not obtained the return of spontaneous circulation (ROSC). Such cardiopulmonary resuscitation (CPR) is called ECPR. ECPR can benefit some patients with cardiac arrest, however, there are still some problems and puzzles in the implementation of ECPR, such as the implementation location of ECPR patients? Select mechanical press or manual press before ECPR start? Can ECPR be used in special patients, such as traumatic cardiac arrest (TCA), aortic dissection and immunosuppressed patients? The age limit of ECPR and the ethical issues related to ECPR. Based on the research status at home and abroad, this paper analyzes and expounds these problems, hoping to provide new ideas for the research and application of ECPR by the majority of domestic colleagues engaged in cardiopulmonary resuscitation.
目的 利用大动物评价新型国产体外膜肺氧合器(extracorporeal membrane oxygenation,ECMO)主机的运行效果及安全性,为进一步的临床应用提供依据.方法 选择国产健康雄性白猪5头,体质量(51±4)kg,应用新型国产ECMO主机配合进口膜氧合器与管路建立ECMO系统,持续运行72 h.ECMO设定参数为:静脉-动脉ECMO模式,离心泵转速3000~3500 r/min,持续输注肝素维持活化凝血时间(activate clotting time,ACT)在 140~200 s.实时监测转速、流量、泵前压力、泵后压力、膜后压力等设备参数情况,并进行设备性能评分.动态监测动物血流动力学、乳酸、血常规等指标的变化.组内不同时间点比较,采用重复测量方差分析.于实验终点,观察泵头和氧合器内的血栓形成情况,处死动物获取主要器官的组织标本,进行大体肉眼观察及病理损伤评估.结果 所有动物均成功运行ECMO系统72 h.(1)离心泵转速维持在 3 029~3 483 r/min,流量维持在 2.24~2.60 L/min,泵前压力-107.57~-31.86 mmHg,泵后压力197.50~282.43 mmHg,膜后压力178.71~261.5 mmHg,均处于合理范围,不同时间点比较差异无统计学意义(均P>0.05).主机性能评分均在4分及以上,满足使用要求.(2)动物心率为50~80次/min,平均动脉压为85~115 mmHg,乳酸0.996~2.25 mmol/L,均处于正常范围,不同时间点比较差异无统计学意义(均P>0.05);游离血红蛋白为8.98~16.39 mg/L,血红蛋白为6.58~7.52 g/L,均处于合理范围,不同时间点比较差异无统计学意义(均P>0.05);血小板为69.6~231.6× 109/L,且呈持续下降趋势(P<0.05).ACT维持在135~169 s,位于目标范围内,不同时间点比较差异无统计学意义(P>0.05).(3)实验终点观察泵头和氧合器未见明显血栓,心、脑、肝、肺、肾大体肉眼观未见明显血栓和梗死病灶、显微镜下未见明显出血和坏死等表现.结论 新型国产ECMO主机联合进口膜氧合器和管路建立的ECMO顺利运行72 h,达到目标的效果和安全性.
目的:总结气管支气管损伤(tracheobronchial injury, TBI)的治疗经验,探讨气管支架在TBI治疗中的应用价值。方法:对2015年7月至2022年6月期间在浙江大学医学院附属第二医院急诊科确诊的TBI患者的临床资料进行回顾性分析,总结各项治疗方法尤其是气管支架治疗的优势,评估综合应用各项治疗方法后患者的整体疗效。TBI的确诊方法为:有损伤病史和临床表现的疑似患者,最终经胸部CT或气管镜检查确诊。治疗方法包括:先通过气管插管/切开、机械通气、经气管镜治疗、体外膜肺氧合(extracorporeal membrane oxygenation, ECMO)治疗等为患者建立安全的气道、保证有效通气,再选择手术治疗、气管支架治疗或保守治疗等。结果:共25例患者,全部接受了气管插管/切开、机械通气、经气管镜治疗,3例接受了ECMO治疗;手术治疗4例、气管支架置入5例,保守治疗16例;共5例患者死亡。5例患者金属支架留置时间2~3周,1例硅酮支架留置时间371 d,期间均未见明显支架移位,支架取出后随访6个月以上,均未见气道狭窄。结论:TBI患者多病情危重、病死率高,常需要机械通气、外科手术、气管支架,甚至ECMO等进行综合治疗。气管支架对气管支气管塌陷、狭窄的治疗简单有效,能替代部分手术治疗,值得推广。
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is indicated in patients with severe cardiogenic shock. During extracorporeal membrane oxygenation (ECMO) use, systemic anticoagulation is generally used to ensure the normal functioning of ECMO. Hemorrhage and thrombosis are two important complications of ECMO. However, despite adequate anticoagulation, some patients still experience thrombosis, such as inferior vena cava thrombosis (IVCT), after the removal of ECMO.[1,2] A meta-analysis showed that the incidence of venous thrombosis during ECMO treatment is approximately 10%,[3] but IVCT is rarely reported. We report two cases of IVCT after the removal of VA-ECMO cannulas.
OBJECTIVE:To investigate the protective effect and potential mechanism of tubastatin A (TubA), a specific inhibitor of histone deacetylase 6 (HDAC6), on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in swine.METHODS:Twenty-five healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 10) and TubA intervention group (n = 9) using a random number table. The porcine model of CPR was reproduced by 9-minute cardiac arrest induced by electrical stimulation via right ventricle followed by 6-minute CPR. The animals in the Sham group only underwent the regular operation including endotracheal intubation, catheterization, and anesthetic monitoring. At 5 minutes after successful resuscitation, a dose of 4.5 mg/kg of TubA was infused via the femoral vein within 1 hour in the TubA intervention group. The same volume of normal saline was infused in the Sham and CPR model groups. Venous samples were collected before modeling and 1, 2, 4, 24 hours after resuscitation, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in serum were determined by enzyme-linked immunoadsordent assay (ELISA). At 24 hours after resuscitation, the upper pole of left kidney and terminal ileum were harvested to detect cell apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) were detected by Western blotting.RESULTS:After resuscitation, renal dysfunction and intestinal mucous injury were observed in the CPR model and TubA intervention groups when compared with the Sham group, which was indicated by significantly increased levels of SCr, BUN, I-FABP and DAO in serum. However, the serum levels of SCr and DAO starting 1 hour after resuscitation, the serum levels of BUN starting 2 hours after resuscitation, and the serum levels of I-FABP starting 4 hours after resuscitation were significantly decreased in the TubA intervention group when compared with the CPR model group [1-hour SCr (μmol/L): 87±6 vs. 122±7, 1-hour DAO (kU/L): 8.1±1.2 vs. 10.3±0.8, 2-hour BUN (mmol/L): 12.3±1.2 vs. 14.7±1.3, 4-hour I-FABP (ng/L): 661±39 vs. 751±38, all P < 0.05]. The detection of tissue samples indicated that cell apoptosis and necroptosis in the kidney and intestine at 24 hours after resuscitation were significantly greater in the CPR model and TubA intervention groups when compared with the Sham group, which were indicated by significantly increased apoptotic index and markedly elevated expression levels of RIP3 and MLKL. Nevertheless, compared with the CPR model group, renal and intestinal apoptotic indexes at 24 hours after resuscitation in the TubA intervention group were significantly decreased [renal apoptosis index: (21.4±4.6)% vs. (55.2±9.5)%, intestinal apoptosis index: (21.3±4.5)% vs. (50.9±7.0)%, both P < 0.05], and the expression levels of RIP3 and MLKL were significantly reduced [renal tissue: RIP3 protein (RIP3/GAPDH) was 1.11±0.07 vs. 1.39±0.17, MLKL protein (MLKL/GAPDH) was 1.20±0.14 vs. 1.51±0.26; intestinal tissue: RIP3 protein (RIP3/GAPDH) was 1.24±0.18 vs. 1.69±0.28, MLKL protein (MLKL/GAPDH) was 1.38±0.15 vs. 1.80±0.26, all P < 0.05].CONCLUSIONS:TubA has the protective effect on alleviating post-resuscitation renal dysfunction and intestinal mucous injury, and its mechanism may be related to inhibition of cell apoptosis and necroptosis.
急性呼吸窘迫综合征(ARDS)是严重创伤的常见和严重并发症之一,常常导致患者死亡。体外膜肺氧合(ECMO)作为当前心肺功能支持的终极手段,在ARDS救治过程中发挥越来越重要的作用。体外生命支持组织(ELSO)建议ECMO治疗时间一般为2周,如果病情没有改善,考虑到成本效益因素则退出ECMO治疗。本院一例严重创伤后并发ARDS患者,经过46 d长程静脉-静脉体外膜肺氧合(VV-ECMO治疗获得成功,国内外文献少见,现报道如下。
AimThe primary mission of cardiopulmonary resuscitation (CPR) is to provide adequate blood flow and oxygen delivery for restoring spontaneous circulation from cardiac arrest (CA) events. Previously, studies demonstrated that chest compression synchronized ventilation (CCSV) improved systemic oxygen supply during CPR, and aortic balloon occlusion (ABO) augments the efficacy of external CPR by increasing blood perfusion to vital organs. However, both them failed to make a significant improvement in return of spontaneous circulation (ROSC). In this study, we investigated the effects of combined CCSV and ABO on the outcomes of CPR in swine.MethodsThirty-one male domestic swine were subjected to 8 min of electrically induced and untreated CA followed by 8 min of CPR. CPR was performed by continuous chest compressions and mechanical ventilation. At the beginning of CPR, the animals were randomized to receive intermittent positive pressure ventilation (IPPV, n = 10), CCSV (n = 7), IPPV + ABO (n = 7), or CCSV + ABO (n = 7). During CPR, gas exchange and systemic hemodynamics were measured, and ROSC was recorded. After resuscitation, the function and injury biomarkers of vital organs including heart, brain, kidney, and intestine were evaluated.ResultsDuring CPR, PaO2 was significantly higher accompanied by significantly greater regional cerebral oxygen saturation in the CCSV and CCSV + ABO groups than the IPPV group. Coronary perfusion pressure, end-tidal carbon dioxide, and carotid blood flow were significantly increased in the IPPV + ABO and CCSV + ABO groups compared with the IPPV group. ROSC was achieved in five of ten (IPPV), five of seven (CCSV), six of seven (IPPV + ABO), and seven of seven (CCSV + ABO) swine, with the rate of resuscitation success being significantly higher in the CCSV + ABO group than the IPPV group (P = 0.044). After resuscitation, significantly improved myocardial and neurological function, and markedly less cardiac, cerebral, renal, and intestinal injuries were observed in the CCSV + ABO group compared with the IPPV group.ConclusionThe combination of CCSV and ABO improved both ventilatory and hemodynamic efficacy during CPR, promoted ROSC, and alleviated post-resuscitation multiple organ injury in swine.
目的 探讨丙戊酸钠(sodium valproate,VPA)对猪心肺复苏(cardiopulmonary resuscitation,CPR)后心脑损伤的作用及机制.方法 国产健康雄性白猪25头,体质量(37±3)kg,随机(随机数字法)为假手术组(Sham,n=6)、CPR组(n=10)与CPR+VPA组(n=9).经右心室电极释放交流电诱发心脏骤停9 min,然后CPR 6 min,以此制备猪心脏骤停-复苏模型.CPR+VPA组在复苏后5 min利用微量输液泵经股静脉泵入VPA 150 mg/kg,持续1 h.于复苏后1 h、2 h、4 h和24 h,经股静脉采集血液标本,应用ELISA法检测心肌肌钙蛋白(cardiac troponin I,cTnl)、肌酸激酶同工酶(creatine kinase MB,CKMB)、神经元特异度烯醇化酶(neuron specific enolase,NSE)和S100B蛋白(S100B protein,S100B).复苏后24 h对动物实施安乐死,迅速获取左室心肌和大脑皮层组织标本,应用Western blot法检测C/EBP同源蛋白(C/EBP homologous protein,CHOP)、半胱氨酸天冬氨酸蛋白酶12(caspase 12)和caspase 3的蛋白表达水平,TUNEL法检测细胞凋亡水平.三组间的计量资料比较,采用单因素方差分析.结果 与Sham组相比,CPR组和CPR+VPA组复苏后心脑损伤标志物cTnl、CKMB、NSE和S100B的血清浓度均明显升高(均P<0.05).与CPR组相比,CPR+VPA组cTnI和NSE在复苏l h后、CKMB和S100B在复苏2h后的血清浓度显著降低(均P<0.05)o CPR组和CPR+VPA组复苏后心脑组织内质网应激凋亡相关蛋白CHOP、caspase 12和caspase 3表达较Sham组明显增加,细胞凋亡指数显著升高(均P<0.05).而CPR+VPA组心脑组织的CHOP、caspase 12和caspase 3较CPR组明显减少,细胞凋亡程度显著降低(均P<0.05).结论 VPA具有减轻猪CPR后心脑损伤的作用,其机制可能与抑制内质网应激途径介导的细胞凋亡过程有关.
目的 研究丙戊酸钠对猪心肺复苏(CPR)后肾肠损伤的作用,并探讨是否影响内质网应激-凋亡的途径.方法 选用25头健康雄性白猪,应用随机数字表法分入假手术组、复苏组与丙戊酸钠组.以电刺激诱发室颤9 min+复苏6 min制备猪心脏骤停(CA)-复苏模型,假手术组仅进行动物准备工作.丙戊酸钠组在复苏后5 min时应用微量输液泵在1 h内静脉泵入150 mg/kg丙戊酸钠,假手术组和复苏组同法泵入等量溶媒.获取各组动物复苏后1 h、2 h、4 h和24 h的静脉血标本,以及复苏后24 h的肾肠组织样本,应用ELISA法检测血清肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen,BUN)、肠型脂肪酸结合蛋白(intestinal fatty acid binding protein,IFABP)和二胺氧化酶(diamine oxidase,DAO)浓度,以及Western blot法与TUNEL法检测肾肠组织C/EBP同源蛋白(C/EBP homologous protein,CHOP)、半胱氨酸天冬氨酸蛋白酶(caspase)-12、caspase-3的蛋白表达和细胞凋亡的程度.结果 ①在复苏后24 h观察期间,复苏组和丙戊酸钠组较假手术组血清Cr、BUN、IFABP和DAO浓度明显升高(均P<0.05).丙戊酸钠组在复苏后24 h期间血清Cr和IFABP浓度、在复苏2 h后血清BUN和DAO浓度明显低于复苏组(均P<0.05).②在复苏后24 h,复苏组和丙戊酸钠组较假手术组肾肠组织内质网应激-凋亡指标明显异常,表现为CHOP、caspase-12和caspase-3蛋白表达明显增加,细胞凋亡指数明显升高(均P<0.05);而丙戊酸钠组较复苏组肾肠组织内质网应激和细胞凋亡程度明显减轻(均P<0.05).结论 丙戊酸钠可能通过抑制内质网应激-凋亡途径而对复苏后猪肾肠损伤发挥保护作用,值得进一步研究.
Severe trauma can result in severe respiratory and circulatory failure with a high mortality rate,which is quite difficult for clinical treatment. In recent years,the application of extracorporeal membrane oxygenation(ECMO)to circulatory and/or respiratory failure caused by severe trauma has received more and more attention. Systemic anticoagulation is often considered as a relative contraindication to ECMO therapy in patients with severe trauma who are at higher risk of bleeding. However,recent studies have shown that venovenous(VV)-ECMO is safe and feasible for treatment of severe acute respiratory failure after trauma,and venoarterial(VA)-ECMO is of great value for treatment of cardiogenic shock and traumatic cardiac arrest. The issues such as the timing of application,anticoagulation strategies,impact on survival and risk-benefit evaluation related to ECMO application to trauma care need to be investigated further. In this study,the authors summarize advances in application of ECMO,prevention and management of related complications in patients with severe trauma,so as to provide a reference for improving the application level of ECMO.
Gastric perforation is a rare complication of cardiopulmonary resuscitation (CPR), mostly resulting from incorrect airway management. If left unrecognized, it is associated with high mortality and morbidity. We present a case of gastric perforation after improper CPR. A 56-year-old drunken male was sent to the emergency department due to coma after fall onto the ground. He was thought to have cardiac arrest at scene and was saved with CPR maneuver by his friends who has never been trained before. He was taken to the hospital by emergency medical service personnel and presented with abdominal distention and extensive pneumoperitoneum. Emergency laparotomy was performed which revealed gastric perforation at the lesser curvature of the stomach. The laceration was repaired without any difficulty and the patient was discharged home without any neurological deficit. The aim of this report is to remind the public and emergency physicians that gastric perforation should be suspected in patients with distended abdomen and pneumoperitoneum after CPR. Because the most common risk factor for CPR-related gastric perforation is the bystander-provided resuscitation, it is encouraged for the public to take formal CPR training.
OBJECTIVE:This study aimed to investigate the clinical outcomes of endoscopic transnasal optic canal decompression (ETOCD) for patients with indirect traumatic optic neuropathy (TON) and identify the relevant prognostic factors. METHODS:Seventy-two indirect TON patients who underwent ETOCD surgery from August 2017 to May 2019 were analyzed retrospectively. The paired t-test was used to compare the visual acuity (VA) before and after ETOCD, and multiple linear regression analysis was used to distinguish the potential prognostic factors. RESULTS:Among the patients analyzed, postoperative VA (-2.87 ± 0.19) was significantly higher than the preoperative VA (-3.92 ± 0.13) (P < 0.05). Multiple linear regression analysis models showed that poor initial VA and longer time to surgery were independent risk factors for VA prognosis (P < 0.05), but surgical time alone was significantly associated with the improvement degree of visual acuity (IDVA) (P < 0.05). Optic canal fracture, orbital fracture, and hemorrhage within the ethmoid and/or sphenoid sinus were not significantly correlated with IDVA and VA prognosis (P > 0.05). CONCLUSIONS:ETOCD surgery could salvage VA impairment in patients with indirect TON. A better initial VA indicates better final VA outcomes after surgery. Additionally, shorter time to surgery implies better VA prognosis and higher IDVA.
重症新型冠状病毒肺炎(corona virus disease 2019, COVID-19)患者以严重低氧血症为特征,如果传统的治疗手段无法纠正顽固性低氧血症或者出现明显心脏功能损害,可考虑应用体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)技术进行补救性治疗 [1-2].