establishment-of-deep-hypothermic-circulatory-arrest-in-rats

Establishment of Deep Hypothermic Circulatory Arrest in Rats

Deep hypothermic circulatory arrest (DHCA) is routinely applied during surgeries for complex congenital heart disease and aortic arch disease. The present ...

effects-extracorporeal-membrane-oxygenation-on-coagulation

Effects of Extracorporeal Membrane Oxygenation on the Coagulation System

This study aimed to investigate the effects of long-term awake extracorporeal membrane oxygenation (ECMO) on the coagulation system in a sheep model. A ...

Peking Union Medical College

Capital Medical University

Extracorporeal membrane oxygenation (ECMO) is an imperative short-term cardiopulmonary support device now. We aimed to provide a single-center experience of veno-arterial (V-A) ECMO management and identify the risk factors of in-hospital mortality.

Outcomes from adult veno-arterial extracorporeal membrane oxygenation in a cardiovascular disease center from 2009 to 2019.

The erector spinae plane block is a novel regional anesthetic technique that is gaining popularity in pediatrics. However, the efficacy of erector spinae plane block in children is unclear. The aim of the systematic review and meta-analysis was to investigate effects of erector spinae plane block on postoperative pain relief in children.

Effects of erector spinae plane block on postoperative pain in children undergoing surgery: A systematic review and meta-analysis of randomized controlled trials.

 Extracorporeal membrane oxygenation (ECMO) provides cardiopulmonary support for critically ill patients. Portable ECMO devices can be applied in both in-hospital and out-of-hospital emergency conditions. We evaluated the safety and biocompatibility of a novel centrifugal pump and ECMO device of the OASSIST ECMO System (Jiangsu STMed Technologies Co., Suzhou, China) in a 168-h ovine ECMO model.  The portable OASSIST ECMO system consists of the control console, the pump drive, and the disposable centrifugal pump. Ten healthy sheep were used to evaluate the OASSIST ECMO system. Five were supported on veno-venous ECMO and five on veno-arterial ECMO, each for 168 h. The systemic anticoagulation was achieved by continuous heparin infusion to maintain the activated clotting time (ACT) between 220 and 250 s. The rotary speed was set at 3,200-3,500 rpm. The ECMO configurations and ACT were recorded every 6 hours (h). The free hemoglobin (fHb), complete blood count, and coagulation action test were monitored, at the 6th h and every 24 h after the initiation of the ECMO. The dissection of the pump head and oxygenator were conducted to explore thrombosis.  Ten sheep successfully completed the study duration without device-related accidents. The pumps ran stably, and the ECMO flow ranged from 1.6 ± 0.1 to 2.0 ± 0.11 L/min in the V-V group, and from 1.8 ± 0.1 to 2.4 ± 0.14 L/min in the V-A group. The anticoagulation was well-performed. The ACT was maintained at 239.78 ± 36.31 s, no major bleeding or thrombosis was observed during the ECMO run or in the autopsy. 3/5 in the V-A group and 4/5 in the V-V group developed small thrombus in the bearing pedestal. No obvious thrombus formed in the oxygenator was observed. The hemolytic blood damage was not significant. The average fHb was 0.17 ± 0.12 g/L. Considering hemodilution, the hemoglobin, white blood cell, and platelets didn't reduce during the ECMO runs.  The OASSIST ECMO system shows satisfactory safety and biocompatibility for the 168-h preclinical evaluation in the ovine model. The OASSIST ECMO system is promising to be applied in clinical conditions in the future.

Safety and Efficacy of a Novel Centrifugal Pump and Driving Devices of the OASSIST ECMO System: A Preclinical Evaluation in the Ovine Model.

 Large animal models are developed to help understand physiology and explore clinical translational significance in the continuous development of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) technology. The purpose of this study was to investigate the establishment methods and management strategies in an ovine model of VA-ECMO.  Seven sheep underwent VA-ECMO support for 7 days by cannulation  the right jugular vein and artery. The animals were transferred into the monitoring cages after surgery and were kept awake after anesthesia recovery. The hydraulic parameters of ECMO, basic hemodynamics, mental state, and fed state of sheep were observed in real time. Blood gas analysis and activated clotting time (ACT) were tested every 6 h, while the complete blood count, blood chemistry, and coagulation tests were monitored every day. Sheep were euthanized after 7 days. Necropsy was performed and the main organs were removed for histopathological evaluation.  Five sheep survived and successfully weaned from ECMO. Two sheep died within 24-48 h of ECMO support. One animal died of fungal pneumonia caused by reflux aspiration, and the other died of hemorrhagic shock caused by bleeding at the left jugular artery cannulation site used for hemodynamic monitoring. During the experiment, the hemodynamics of the five sheep were stable. The animals stayed awake and freely ate hay and feed pellets and drank water. With no need for additional nutrition support or transfusion, the hemoglobin concentration and platelet count were in the normal reference range. The ECMO flow remained stable and the oxygenation performance of the oxygenator was satisfactory. No major adverse pathological injury occurred.  The perioperative management strategies and animal care are the key points of the VA-ECMO model in conscious sheep. This model could be a platform for further research of disease animal models, pathophysiology exploration, and new equipment verification.

An Ovine Model of Awake Veno-Arterial Extracorporeal Membrane Oxygenation.

Red blood cell (RBC) transfusion is associated with adverse outcomes, but there are few studies on the RBC volume. This study aimed to evaluate the relationship between intraoperative RBC volume and postoperative adverse outcomes for on-pump cardiac surgery.

Dose-dependent influence of red blood cell transfusion volume on adverse outcomes in cardiac surgery.

Epidemiological characteristics of all-cause mortality reviewing out-hospital death under the clouds of COVID-19.

Deep hypothermic circulatory arrest (DHCA) can induce systemic inflammatory response syndrome, including neuroinflammation. Finding suitable compounds is necessary for attenuating neuroinflammation and avoiding cerebral complications following DHCA. In the present study, we established DHCA rat models and monitored the vital signs during the surgical process. After surgery, we found significantly increased proinflammatory cytokines (IL-6, IL-1β, and TNF-α) in DHCA rats. Quantitative proteomics analysis was performed for exploring the differentially expressed proteins in hippocampus of DHCA rats and the data showed the adiponectin receptor 1 protein was upregulated. More importantly, administration of AdipoRon, a small-molecule adiponectin receptor agonist, could improve the basic vital signs and attenuate the increased IL-6, IL-1β, and TNF-α in DHCA rats. Furthermore, AdipoRon inhibits the activation of microglia (M1 state) and promotes their transition to an anti-inflammatory state, via promoting the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), and downregulating nuclear factor kappa B (NF-κB) in DHCA rats. Consistently, we used LPS-treated BV2 cells to mimic the neuroinflammatory condition and found that AdipoRon dose-dependently decreased cytokines, along with increased phosphorylation of AMPK and downregulated NF-κB. In conclusion, our present data supported that AdipoRon inhibited DHCA-induced neuroinflammation via activating the hippocampal AMPK/NF-κB pathway.

AdipoRon Inhibits Neuroinflammation Induced by Deep Hypothermic Circulatory Arrest Involving the AMPK/NF-κB Pathway in Rats.

Neurologic abnormalities occurring after deep hypothermic circulatory arrest (DHCA) remain a significant concern. However, molecular mechanisms leading to DHCA-related cerebral injury are still ill-defined. Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and can play important roles in different types of cerebral injury. This study aimed to investigate circRNAs expression profiles in rat hippocampus after DHCA and explore the potential functions of circRNAs in DHCA-related cerebral injury. Hence, the DHCA procedure in rats was established and a transcriptomic profiling of circRNAs in rat hippocampus was done. As a result, a total of 35192 circRNAs were identified. Among them, 339 circRNAs were dysregulated, including 194 down-regulated and 145 up-regulated between DHCA and sham group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed based on the host genes of all dysregulated circRNAs. Also, 4 circRNAs were validated by RT-qPCR (rno_circ_0028462, rno_circ_0037165, rno_circ_0045161 and rno_circ_0019047). Then a circRNA-microRNA (miRNA) interaction network involving 4 candidate circRNAs was constructed. Furthermore, functional enrichment analysis of the miRNA-targeting mRNAs of every candidate circRNA was conducted to gain insight into each of the 4 circRNAs. Our study provided a better understanding of circRNAs in the mechanisms of DHCA-related cerebral injury and some potential targets for neuroprotection.

Transcriptomic Profiling of circRNAs in rat Hippocampus after Deep Hypothermic Circulatory Arrest.

Sepsis is an unusual systemic reaction with high mortality and secondary septic liver injury is proposed to be the major cause of mortality. Extracorporeal membrane oxygenation (ECMO) can enhance terminal organ perfusion by elevating circulatory support which is used in severe sepsis patients. However, the interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response. Besides, inflammation and apoptosis are the main mediators in the pathophysiology of septic liver injury. Therefore, we investigated the protective effect of Deoxyribonuclease I (DNase I) against septic liver injury supported by ECMO in rats. Sepsis was induced by lipopolysaccharide (LPS) and 24 hours after the administration, the rats were treated with ECMO. Then blood samples and liver tissues were collected. DNase I significantly attenuated the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and significantly decreased hepatic levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, myeloperoxidase (MPO), downstream inflammatory factor interleukin-1 β (IL-1 β ) and interleukin-18 (IL-18), and improved neutrophil infiltration. Additionally, DNase I significantly reduced the expression of apoptosis key protein and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-labeled apoptotic hepatocytes. In summary, our findings demonstrated that DNase I alleviates liver injury in ECMO-supported septic rats by reducing the inflammatory and apoptotic responses.

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation.

To examine the correlation between the preoperative elevated aspartate aminotransferase (AST)/alanine transaminase (ALT) (De Ritis) ratio and the drainage volume in patients after aortic arch surgery.

ArticleTotal : 2	Year
Publication title Cited by 5	2022
Publication title	2024

Article	Year
Outcomes from adult veno-arterial extracorporeal membrane oxygenation in a cardiovascular disease center from 2009 to 2019. Perfusion\| PubMed ID: 33588661	2022
Effects of erector spinae plane block on postoperative pain in children undergoing surgery: A systematic review and meta-analysis of randomized controlled trials. Paediatric anaesthesia\| PubMed ID: 34270146	2021
Safety and Efficacy of a Novel Centrifugal Pump and Driving Devices of the OASSIST ECMO System: A Preclinical Evaluation in the Ovine Model. Frontiers in medicine\| PubMed ID: 34708051	2021
An Ovine Model of Awake Veno-Arterial Extracorporeal Membrane Oxygenation. Frontiers in veterinary science\| PubMed ID: 35004934	2021
Dose-dependent influence of red blood cell transfusion volume on adverse outcomes in cardiac surgery. Perfusion\| PubMed ID: 35839260	2022
Epidemiological characteristics of all-cause mortality reviewing out-hospital death under the clouds of COVID-19. Chinese medical journal\| PubMed ID: 35916541	2022
AdipoRon Inhibits Neuroinflammation Induced by Deep Hypothermic Circulatory Arrest Involving the AMPK/NF-κB Pathway in Rats. Pharmaceutics\| PubMed ID: 36432657	2022
Transcriptomic Profiling of circRNAs in rat Hippocampus after Deep Hypothermic Circulatory Arrest. International journal of medical sciences\| PubMed ID: 37082735	2023
Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation. ASAIO journal (American Society for Artificial Internal Organs : 1992)\| PubMed ID: 37923309	2023
Elevated AST/ALT (De Ritis) Ratio is a Risk Factor of Drainage Volume after Aortic Arch Surgery. The heart surgery forum\| PubMed ID: 38178336	2023

Weidong Yan

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