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      Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs

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          Abstract

          Extracorporeal membrane oxygenation (ECMO) was established as a treatment for severe cardiac or respiratory disease. Intra-device clot formation is a common risk. This is based on complex coagulation phenomena which are not yet sufficiently understood. The objective was the development and validation of a methodology to capture the key properties of clots deposed in membrane lungs (MLs), such as clot size, distribution, burden, and composition. One end-of-therapy PLS ML was examined. Clot detection was performed using multidetector computed tomography (MDCT), microcomputed tomography (μCT), and photography of fiber mats (fiber mat imaging, FMI). Histological staining was conducted for von Willebrand factor (vWF), platelets (CD42b, CD62P), fibrin, and nucleated cells (4′, 6-diamidino-2-phenylindole, DAPI). The three imaging methods showed similar clot distribution inside the ML. Independent of the imaging method, clot loading was detected predominantly in the inlet chamber of the ML. The μCT had the highest accuracy. However, it was more expensive and time consuming than MDCT or FMI. The MDCT detected the clots with low scanning time. Due to its lower resolution, it only showed clotted areas but not the exact shape of clot structures. FMI represented the simplest variant, requiring little effort and resources. FMI allowed clot localization and calculation of clot volume. Histological evaluation indicated omnipresent immunological deposits throughout the ML. Visually clot-free areas were covered with leukocytes and platelets forming platelet-leukocyte aggregates (PLAs). Cells were embedded in vWF cobwebs, while vWF fibers were negligible. In conclusion, the presented methodology allowed adequate clot identification and histological classification of possible thrombosis markers such as PLAs.

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          The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

          Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient’s blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.
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            Systemic inflammatory response syndrome.

            Localized inflammation is a physiological protective response which is generally tightly controlled by the body at the site of injury. Loss of this local control or an overly activated response results in an exaggerated systemic response which is clinically identified as systemic inflammatory response syndrome (SIRS). Compensatory mechanisms are initiated in concert with SIRS and outcome (resolution, multiple organ dysfunction syndrome or death) is dependent on the balance of SIRS and such compensatory mechanisms. No directed therapies have been successful to date in influencing outcome. This review examines the current spectrum and pathophysiology of SIRS. Further clinical and basic scientific research is required to develop the global picture of SIRS, its associated family of syndromes and their natural histories.
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              The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli

              Although arterial and venous thromboembolic disorders are among the most frequent causes of mortality and morbidity, there has been little description of how the composition of thrombi and emboli depends on their vascular origin and age. We quantified the structure and composition of arterial and venous thrombi and pulmonary emboli using high-resolution scanning electron microscopy. Arterial thrombi contained a surprisingly large amount of fibrin, in addition to platelets. The composition of pulmonary emboli mirrored the most distal part of venous thrombi from which they originated, which differed from the structure of the body and head of the same thrombi. All thrombi and emboli contained few biconcave red blood cells but many polyhedrocytes or related forms of compressed red blood cells, demonstrating that these structures are a signature of clot contraction in vivo. Polyhedrocytes and intermediate forms comprised the major constituents of venous thrombi and pulmonary emboli. The structures within all of the thrombi and emboli were very tightly packed, in contrast to clots formed in vitro. There are distinctive, reproducible differences among arterial and venous thrombi and emboli related to their origin, destination and duration, which may have clinical implications for the understanding and treatment of thrombotic disorders.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2616084/overviewRole: Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2175397/overviewRole: Role: Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2221202/overviewRole: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2609077/overviewRole: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2764664Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1936831/overviewRole: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1103129/overviewRole: Role: Role: Role: Role: Role:
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                19 June 2024
                2024
                : 11
                : 1416319
                Affiliations
                [1] 1Department of Cardiothoracic Surgery, University Hospital Regensburg , Regensburg, Germany
                [2] 2Department of Biofluid Mechanics, Faculty of Mechanical Engineering, Technical University of Applied Sciences (OTH) Regensburg , Regensburg, Germany
                [3] 3Regensburg Center of Biomedical Engineering, Facility of University Regensburg and Technical University of Applied Sciences (OTH) Regensburg , Regensburg, Germany
                [4] 4Department of Internal Medicine II, University Hospital Regensburg , Regensburg, Germany
                Author notes

                Edited by: Matteo Becatti, University of Firenze, Italy

                Reviewed by: Jacky Y. Suen, The University of Queensland, Australia

                Zengsheng Chen, Beihang University, China

                *Correspondence: Karla Lehle, karla.lehle@ 123456ukr.de

                These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fmed.2024.1416319
                11219572
                38962744
                50483c11-2c48-492b-bf9d-f1327ae9b97c
                Copyright © 2024 Wagner, Kranz, Krenkel, Pointner, Foltan, Lubnow and Lehle.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 April 2024
                : 06 June 2024
                Page count
                Figures: 8, Tables: 2, Equations: 0, References: 52, Pages: 14, Words: 10125
                Funding
                Funded by: German Research Foundation [Deutsche Forschungsgemeinschaft (DFG)]
                Funded by: University of Regensburg, Germany
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the German Research Foundation [Deutsche Forschungsgemeinschaft (DFG)] as part of the priority program SPP 2014 “Towards an Implantable Lung” (no. 447721607). Open Access funding was supported by institutional grants from the University of Regensburg, Germany.
                Categories
                Medicine
                Original Research
                Custom metadata
                Intensive Care Medicine and Anesthesiology

                ecmo,membrane lung,μct,mdct,shear induced clotting,vwf,histological evaluation

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