Gabrielle D Briggs, Simone Meakes, Kate L King, Zsolt J Balogh
{"title":"Cell-free mitochondria are detected in high concentrations in the plasma of orthopedic trauma patients.","authors":"Gabrielle D Briggs, Simone Meakes, Kate L King, Zsolt J Balogh","doi":"10.1097/TA.0000000000004483","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Trauma and surgery can derange inflammatory and hemostasis responses, potentially leading to multiple organ failure. Mitochondrial damage-associated molecular patterns are known to be part of the pathomechanism, but their exact origin remains uncertain. Recently, intact mitochondria were detected in healthy individuals' peripheral blood, which suggested a potential role in inflammation.</p><p><strong>Methods: </strong>In this case-control study, we quantitated cell-free mitochondria in the blood of healthy subjects (n = 4) and trauma patients (n = 25) and assessed their relationship with patient demographics, injury and shock severity, markers of tissue injury, inflammation, and blood transfusions. Blood samples were collected before and after major orthopedic trauma surgery, and cell-free mitochondria were quantified using flow cytometry, targeting the outer mitochondrial membrane protein, TOMM70. Mitotracker Deep Red staining was used to assess mitochondrial membrane potential.</p><p><strong>Results: </strong>Trauma patients had significantly more cell-free mitochondria in their plasma compared with healthy controls, with highest counts immediately after surgery. The number of cell-free mitochondria decreased by day 5 postoperatively. Trauma patients exhibited a higher proportion of active cell-free mitochondria compared with healthy controls, especially immediately after surgery, and this proportion correlated with tissue injury markers. Associations were also found with acute thrombocytopenia, Denver multiple organ failure score, and transfusion of fresh frozen plasma and cryoprecipitate.</p><p><strong>Conclusion: </strong>Our findings indicate that the mere high number of cell-free mitochondria in the circulation of trauma patients is not necessarily pro-inflammatory, but their active status is associated with more severe secondary tissue injury. The natural history of cell-free mitochondria in trauma needs to be characterized, including their potential cause-effect relationship with major postinjury complications.</p><p><strong>Level of evidence: </strong>Prognostic and Epidemiological; Level III.</p>","PeriodicalId":17453,"journal":{"name":"Journal of Trauma and Acute Care Surgery","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Trauma and Acute Care Surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/TA.0000000000004483","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Trauma and surgery can derange inflammatory and hemostasis responses, potentially leading to multiple organ failure. Mitochondrial damage-associated molecular patterns are known to be part of the pathomechanism, but their exact origin remains uncertain. Recently, intact mitochondria were detected in healthy individuals' peripheral blood, which suggested a potential role in inflammation.
Methods: In this case-control study, we quantitated cell-free mitochondria in the blood of healthy subjects (n = 4) and trauma patients (n = 25) and assessed their relationship with patient demographics, injury and shock severity, markers of tissue injury, inflammation, and blood transfusions. Blood samples were collected before and after major orthopedic trauma surgery, and cell-free mitochondria were quantified using flow cytometry, targeting the outer mitochondrial membrane protein, TOMM70. Mitotracker Deep Red staining was used to assess mitochondrial membrane potential.
Results: Trauma patients had significantly more cell-free mitochondria in their plasma compared with healthy controls, with highest counts immediately after surgery. The number of cell-free mitochondria decreased by day 5 postoperatively. Trauma patients exhibited a higher proportion of active cell-free mitochondria compared with healthy controls, especially immediately after surgery, and this proportion correlated with tissue injury markers. Associations were also found with acute thrombocytopenia, Denver multiple organ failure score, and transfusion of fresh frozen plasma and cryoprecipitate.
Conclusion: Our findings indicate that the mere high number of cell-free mitochondria in the circulation of trauma patients is not necessarily pro-inflammatory, but their active status is associated with more severe secondary tissue injury. The natural history of cell-free mitochondria in trauma needs to be characterized, including their potential cause-effect relationship with major postinjury complications.
Level of evidence: Prognostic and Epidemiological; Level III.
期刊介绍:
The Journal of Trauma and Acute Care Surgery® is designed to provide the scientific basis to optimize care of the severely injured and critically ill surgical patient. Thus, the Journal has a high priority for basic and translation research to fulfill this objectives. Additionally, the Journal is enthusiastic to publish randomized prospective clinical studies to establish care predicated on a mechanistic foundation. Finally, the Journal is seeking systematic reviews, guidelines and algorithms that incorporate the best evidence available.