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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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Thrombolysis and extracorporeal cardiopulmonary resuscitation for cardiac arrest due to pulmonary embolism:A case report

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World Journal of Critical Care Medicine 2025年第1期14卷 111-117页

作者： Guan-Xing Yuan Zhi-Ping Zhang Jia Zhou Department of Emergency Wuhan Asia General HospitalWuhan 430056Hubei ProvinceChina Department of Neurosurgery Central Theater Command General HospitalWuhan 430000Hubei ProvinceChina

BACKGROUND cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic *** CPR(ECPR)is typically employed as a rescue therapy for selected patients when conventional CPR is failing in settings where it can be *** SUMMARY We present a case of a 69-year-old male who experienced a prolonged cardiac arrest in an ambulance with pulseless electrical *** arrival at the emergency department with ongoing manual chest compressions,bedside pointof-care ultrasound revealed an enlarged right ventricle without *** PE was suspected as the cause of cardiac arrest,and intravenous thrombolytic therapy with 50 mg tissue plasminogen activator was administered during mechanical chest *** 31 minutes of CPR,return of spontaneous circulation was not achieved until 8 minutes after initiation of Veno-arterial extracorporeal membrane oxygenation(ECMO)*** ECMO support,the hemodynamic status and myocardial contractility significantly ***,the patient ultimately did not survive due to intracerebral hemorrhagic complications,leading to death a few days later in the *** This case illustrates the potential of combining systemic thrombolysis with ECPR for refractory cardiac arrest caused by acute PE,but it also highlights the increased risk of significant bleeding complications,including fatal intracranial hemorrhage.

关键词： Pulmonary embolism cardiac arrest Thrombolytic therapy Cardiopulmonary resuscitation Extracorporeal membrane oxygenation Intracranial hemorrhage Case report

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cardiac arrest secondary to pulmonary embolism treated with extracorporeal cardiopulmonary resuscitation:Six case reports

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World Journal of Clinical Cases 2023年第17期11卷 4098-4104页

作者： Min-Shan Qiu Yong-Jin Deng Xue Yang Han-Quan Shao Department of Critical Care Medicine Dongguan People’s HospitalDongguan 523058Guangdong ProvinceChina

BACKGROUND Massive pulmonary embolism(PE)results in extremely high mortality ***-arterial extracorporeal membrane oxygenation(VA-ECMO)can provide circulatory and oxygenation support and rescue patients with massive ***,there are relatively few studies of extracorporeal cardiopulmonary resuscitation(ECPR)in patients with cardiac arrest(CA)secondary to *** aim of the present study is to investigate the clinical use of ECPR in conjunction with heparin anticoagulation in patients with CA secondary to *** SUMMARY We report the cases of six patients with CA secondary to PE treated with ECPR in the intensive care unit of our hospital between June 2020 and June *** six patients experienced witnessed CA whilst in *** had acute onset of severe respiratory distress,hypoxia,and shock rapidly followed by CA and were immediately given cardiopulmonary resuscitation and adjunctive VA-ECMO *** hospitalization,pulmonary artery computed tomography angiography was performed to confirm the diagnosis of *** anticoagulation management,mechanical ventilation,fluid management,and antibiotic treatment,five patients were successfully weaned from ECMO(83.33%),four patients survived for 30 d after discharge(66.67%),and two patients had good neurological outcomes(33.33%).CONCLUSION For patients with CA secondary to massive PE,ECPR in conjunction with heparin anticoagulation may improve outcomes.

关键词： Extracorporeal cardiopulmonary resuscitation cardiac arrest Pulmonary embolism Outcomes Shock Case report

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cardiac arrest, stony heart, and cardiopulmonary resuscitation: An updated revisit

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World Journal of Cardiology 2024年第3期16卷 126-136页

作者： Ayman El-Menyar Bianca M Wahlen Department of Trauma and Vascular Surgery Clinical ResearchHamad Medical CorporationDoha 3050Qatar Department of Clinical Medicine Weill Cornell Medical CollegeDoha 24144Qatar Department of Anesthesiology Hamad Medical CorporationDoha 3050Qatar

The post-resuscitation period is recognized as the main predictor of cardiopul-monary resuscitation(CPR)*** first description of post-resuscitation syndrome and stony heart was published over 50 years *** manifestations may include but are not limited to,persistent precipitating pathology,systemic ischemia/reperfusion response,post-cardiac arrest brain injury,and finally,post-cardiac arrest myocardial dysfunction(PAMD)after successful *** do some patients initially survive successful resuscitation,and others do not?Also,why does the myocardium response vary after resuscitation?These ques-tions have kept scientists busy for several decades since the first successful resuscitation was *** modifying the conventional modalities of resu-scitation together with new promising agents,rescuers will be able to salvage the jeopardized post-resuscitation myocardium and prevent its progression to a dismal,stony *** awareness and staff education are crucial for shortening the resuscitation time and improving short-and long-term *** of these components before and early after the restoration of circulation will enhance the resuscitation *** review extensively addresses the underlying pathophysiology,management,and outcomes of post-resuscitation *** pattern,management,and outcome of PAMD and post-cardiac arrest shock are different based on many factors,including in-hospital cardiac arrest vs out-of-hospital cardiac arrest(OHCA),witnessed vs unwitnessed cardiac arrest,the underlying cause of arrest,the duration,and protocol used for *** restoring spontaneous circulation is a vital sign,it should not be the end of the game or lone primary outcome;it calls for better understanding and aggressive multi-disciplinary interventions and *** development of stony heart post-CPR and OHCA remain the main challenges in emergency and critical care medicine.

关键词： cardiac arrest Out-of-hospital cardiac arrest In-hospital cardiac arrest Post-resuscitation Myocardial dysfunction Cardiopulmonary resuscitation Stony heart

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The neuro-prognostic value of the ion shift index in cardiac arrest patients following extracorporeal cardiopulmonary resuscitation

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World Journal of Emergency Medicine 2023年第5期14卷 354-359页

作者： Gannan Wang Zhe Wang Yi Zhu Zhongman Zhang Wei Li Xufeng Chen Yong Mei Department of Emergency the First Affi liated Hospital of Nanjing Medical UniversityNanjing 210029China Key Laboratory of Emergency and Trauma of Ministry of Education College of Emergency and TraumaHainan Medical UniversityHaikou 571199China

BACKGROUND:The ion shift index(ISI) as a prognostic indicator that can show the severity of hypoxic-ischemic *** aimed to evaluate the performance of the ISI in predicting unfavorable neurological outcomes at hospital discharge in cardiac arrest(CA) patients following extracorporeal cardiopulmonary resuscitation(ECPR) and to compare its performance to other prognostic ***:This was a retrospective observational study including adult CA patients treated with ECPR between January 2018 and December 2022 in a tertiary *** regarding clinical characteristics and laboratory parameters were collected from medical *** ISI was determined based on the first available serum electrolyte levels after *** primary outcome was unfavorable neurological status at hospital discharge,defined as Cerebral Performance Categories 3–*** of the characteristics between the two groups were made using the χ2 test for categorical variables and the t-test or non-parametric Mann-Whitney U-test for continuous variables,as *** analysis was performed using Spearman’s rank correlation coeficient.A two-tailed P-value 3.12 predicted unfavorable outcomes with a sensitivity and specificity of 74.6% and 85.2%,respectively(P<0.001).The prognostic performance of ISI(area under the curve [AUC]=0.887) was similar to that of other predictors,such as gray-to-white matter ratio(AUC=0.850,P=0.433) and neuronspecific enolase(AUC=0.925,P=0.394).CONCLUSION:ISI may be used as a prognostic biomarker

关键词： cardiac arrest Ion shift index Extracorporeal cardiopulmonary resuscitation

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Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway

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Neural Regeneration Research 2022年第10期17卷 2232-2237页

作者： Shi-Rong Lin Qing-Ming Lin Yu-Jia Lin Xin Qian Xiao-Ping Wang Zheng Gong Feng Chen Bin Song Provincial College of Clinical Medicine Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Emergency Medical Center FuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina Department of Human Anatomy School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province FuzhouFujian ProvinceChina Laboratory of Clinical Applied Anatomy Fujian Medical UniversityFuzhouFujian ProvinceChina

Bradykinin(BK)is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective *** previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation(ROSC)after cardiac ***,the precise mechanism underlying this process remains poorly *** this study,we treated a rat model of ROSC after cardiac arrest(induced by asphyxiation)with 150μg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac *** found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest,increased the amount of autophagosomes in the hippocampal tissue,inhibited neuronal cell apoptosis,up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62,inhibited the expression of the brain injury marker S100βand apoptosis-related protein caspase-3,and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related *** monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest,which aggravated the injury caused by *** mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating *** findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.

关键词： autophagy bradykinin cardiac arrest cardiopulmonary resuscitation compound C hippocampus neuron rapamycin restoration of spontaneous circulation

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Timing of brain computed tomography for predicting neurological prognosis in comatose cardiac arrest survivors: a retrospective observational study

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World Journal of Emergency Medicine 2022年第5期13卷 349-354页

作者： Gan-nan Wang Zhong-man Zhang Wen Chen Xiao-quan Xu Jin-song Zhang Department of Emergency the First Affi liated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Radiology the First Affi liated Hospital of Nanjing Medical UniversityNanjing 210029China

BACKGROUND:To assess the association between relevant brain computed tomography(CT)parameters at different time and neurological prognosis in adult comatose survivors after cardiac arrest(CA).METHODS:A total of 94 CA patients who underwent early and late CT scans(within 24 h and 24 h to 7 d respectively after CA)between January 2018 and April 2020 were enrolled in this retrospective *** to the Cerebral Performance Category(CPC)score at hospital discharge,the patients were divided into either a good outcome(CPC 1-2)group or a poor-outcome group(CPC 3-5).The grey-to-white matter ratio(GWR)and the proportion of cerebrospinal fluid volume(pCSFV)were *** predicting poor outcomes,the prognostic performance of relevant CT parameters was evaluated,and the comparison analysis(expressed as the ratio of parameters in late CT to those in the early CT)of diff erent CT time was ***:Totally 26 patients were in the good-outcome group,while 68 patients were in the poor-outcome *** putamen density,GWR,and pCSFV in late CT were significantly lower in the poor-outcome group(P24 h after CA may be a good choice as a neuroimaging approach to evaluating *** predict neurological prognosis,comparison analysis of diff erent CT time can be used as another promising tool in comatose CA survivors.

关键词： cardiac arrest Brain computed tomography Cerebral edema Coma Prognosis

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Magnetic resonance imaging tracing of transplanted bone marrow mesenchymal stem cells in a rat model of cardiac arrest-induced global brain ischemia

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Neural Regeneration Research 2009年第9期4卷 645-653页

作者： Yue Fu Xiangshao Fang Tong Wang Jiwen Wang Jun Jiang Zhigang Luo Xiaohui Duan Jun Shen Zitong Huang Department of Emergency Medicine Second Affiliated Hospital Sun Yat-sen University Guangzhou 510120 Guangdong Province China Institute of Cardiepulmonary Cerebral Resuscitation Sun Yat-sen University Guangzhou 510120 Guangdong Province China Department of Radiology Second Affiliated Hospital Sun Yat-sen University Guangzhou 510120 Guangdong Province China

BACKGROUND： Numerous studies have shown that magnetic resonance imaging （MRI） can detect survival and migration of super paramagnetic iron oxide-labeled stem cells in models of focal cerebral infarction. OBJECTIVE： To observe distribution of bone marrow mesenchymal stem cells （BMSCs） in a rat model of global brain ischemia following cardiac arrest and resuscitation, and to investigate the feasibility of tracing iron oxide-labeled BMSCs using non-invasive MRI. DESIGN, TIME AND SETTING： The randomized, controlled, molecular imaging study was performed at the Linbaixin Medical Research Center, Second Affiliated Hospital, Sun Yat-sen University, and the Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, China from October 2006 to February 2009. MATERIALS： A total of 40 clean, Sprague Dawley rats, aged 6 weeks and of either gender, were supplied by the Experimental Animal Center, Sun Yat-sen University, China, for isolation of BMSCs. Feridex （iron oxide）, Gyroscan Inetra 1.5T MRI system, and cardiopulmonary resuscitation device were used in this study. METHODS： A total of 30 healthy, male Sprague Dawiey rats, aged 6 months, were used to induce ventricular fibrillation using alternating current. After 8 minutes, the rats underwent 6-minute chest compression and mechanical ventilation, followed by electric defibrillation, to establish rat models of global brain ischemia due to cardiac arrest and resuscitation. A total of 24 successful models were randomly assigned to Feridex-labeled and non-labeled groups （n = 12 for each group）. At 2 hours after resuscitation, 5 ×10^8 Feridex-labeled BMSCs, with protamine sulfate as a carrier, and 5 ×10^6 non-labeled BMSCs were respectively transplanted into both groups of rats through the right carotid artery （cells were harvested in 1 mL phosphate buffered saline）. MAIN OUTCOME MEASURES： Feridex-labeled BMSCs were observed by Prussian blue staining and electron microscopy. Signal intensity, celluar viability, a

关键词： bone marrow mesenchymal stem cells cardiac arrest global brain ischemia cerebral resuscitation: maanetic resonance imaaina: transplantation: tracina

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A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study

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World Journal of Emergency Medicine 2024年第1期15卷 16-22页

作者： Jing Yang Hanqi Tang Shihuan Shao Feng Xu Yangyang Fu Shengyong Xu Chen Li Yan Li Yang Liu Joseph Harold Walline Huadong Zhu Yuguo Chen Xuezhong Yu Jun Xu Emergency Department State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Emergency Department Peking University People’s HospitalBeijing 100044China Department of Emergency and Chest Pain Center Shandong Provincial Clinical Research Center for Emergency and Critical Care MedicineKey Laboratory of Emergency and Critical Care Medicine of Shandong ProvinceQilu Hospital of Shandong UniversityJinan 250012China Emergency Department Beijing Jishuitan HospitalBeijing 100035China Emergency Department Tianjin Medical University General HospitalTianjin 300052China Department of Emergency Medicine Penn State Health Milton S.Hershey Medical Center and Penn State College of MedicineHershey 17033USA

BACKGROUND:Unsustained return of spontaneous circulation(ROSC)is a critical barrier to survival in cardiac arrest *** study examined whether end-tidal carbon dioxide(ETCO_(2))and pulse oximetry photoplethysmogram(POP)parameters can be used to identify unsustained ***:We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to ***’general information,ETCO_(2),and POP parameters were collected and statistically ***:The included 105 ROSC episodes(from 80 cardiac arrest patients)comprised 51 sustained ROSC episodes and 54 unsustained ROSC *** 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group(29.2%vs.9.4%,P<0.05).The logistic regression analysis showed that the difference between after and before ROSC in ETCO_(2)(ΔETCO_(2))and the difference between after and before ROCS in area under the curve of POP(ΔAUCp)were independently associated with sustained ROSC(odds ratio[OR]=0.931,95%confi dence interval[95%CI]0.881-0.984,P=0.011 and OR=0.998,95%CI 0.997-0.999,P<0.001).The area under the receiver operating characteristic curve ofΔETCO_(2),ΔAUCp,and the combination of both to predict unsustained ROSC were 0.752(95%CI 0.660-0.844),0.883(95%CI 0.818-0.948),and 0.902(95%CI 0.842-0.962),***:Patients with unsustained ROSC have a poor *** combination ofΔETCO_(2) andΔAUCp showed signifi cant predictive value for unsustained ROSC.

关键词： Return of spontaneous circulation Pulse oximetry photoplethysmogram End-tidal carbon dioxide cardiac arrest Cardiopulmonary resuscitation

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Increasing angiotensin-converting enzyme(ACE)2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest

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World Journal of Emergency Medicine 2022年第3期13卷 208-214页

作者： Hong-li Xiao Lian-xing Zhao Jun Yang Nan Tong Le An Guo-xing Wang Miao-rong Xie Chun-sheng Li Department of Emergency Medicine Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Emergency Internal Medicine the Affiliated Hospital of Qingdao UniversityQingdao 266000China Department of Emergency Medicine Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100050China

BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous *** were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without ***:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial *** blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control *** significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after *** also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 ***:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC i

关键词： Acute pulmonary embolism cardiac arrest Early pulmonary vascular remodeling Angiotensin-converting enzyme

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