Systemic central venous oxygen saturation is associated with clot strength during traumatic hemorrhagic shock: A preclinical observational model

White, Nathan J.; Martin, Erika J.; Shin, Yongyun; Brophy, Donald F.; Diegelmann, Robert F.; Ward, Kevin R.

doi:10.1186/1757-7241-18-64

Cited by 7 publications

(5 citation statements)

References 47 publications

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“…Thromboelastography (TEG; TEG 5,000, Haemoscope, Niles, IL) by recalcification (10 mM final calcium concentration) was performed in whole blood at 37°C 30 min after blood draw as described previously (54). TEG parameters measured included clot onset time (R), clot formation (or kinetics) time (K), clotting angle (Angle), maximal clot strength (MA), and shear elastic modulus (G).…”

Section: Methodsmentioning

confidence: 99%

Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid

Fisher

Kraskauskas

Martin

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

194

199

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Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na+-K+-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

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Section: Methodsmentioning

confidence: 99%

Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid

Fisher

Kraskauskas

Martin

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

194

199

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“…Preclinical studies have primarily focused on evaluating the combined effects of trauma and hemorrhage on coagulation impairments, clotting status, and blood loss. 32 81 82 83 84 85 86 87 88 Hemorrhage severity greatly impacts the metabolic markers, 86 87 physiological and coagulation responses observed in animal models, with varying percentages used to mimic different degrees of blood loss seen in trauma patients. Studies have found that hemorrhage and tissue injury significantly reduced arterial blood pressure, cardiac index, hemoglobin, hematocrit, and platelet count.…”

Section: Resultsmentioning

confidence: 99%

“…Coagulation function was affected by apheresis, hemorrhage, and resuscitation with different solutions, with a reduction in fibrinogen levels resulting in a significant decrease in clot strength. 81 82 83 84 Therapy with high-dose fibrinogen concentrate and the transfusion of platelets were found to restore coagulation function. 85 Also, resuscitation with shed whole blood or FFP has demonstrated greater efficacy than PlasmaLyte in maintaining blood pressure and TEG maximum amplitude.…”

Section: Resultsmentioning

confidence: 99%

The Use of Large Animal Models in Trauma and Bleeding Studies

Rayatdoost,

Grottke

2023

Hamostaseologie

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Background Major trauma often results in significant bleeding and coagulopathy, posing a substantial clinical burden. To understand the underlying pathophysiology and to refine clinical strategies to overcome coagulopathy, preclinical large animal models are often used. This review scrutinizes the clinical relevance of large animal models in hemostasis research, emphasizing challenges in translating findings into clinical therapies. Methods We conducted a thorough search of PubMed and EMBASE databases from January 1, 2010, to December 31, 2022. We used specific keywords and inclusion/exclusion criteria centered on large animal models. Results Our review analyzed 84 pertinent articles, including four animal species: pigs, sheep, dogs, and nonhuman primates (NHPs). Eighty-five percent of the studies predominantly utilized porcine models. Meanwhile, sheep and dogs were less represented, making up only 2.5% of the total studies. Models with NHP were 10%. The most frequently used trauma models involved a combination of liver injury and femur fractures (eight studies), arterial hemorrhage (seven studies), and a combination of hemodilution and liver injury (seven studies). A wide array of coagulation parameters were employed to assess the efficacy of interventions in hemostasis and bleeding control. Conclusions Recognizing the diverse strengths and weaknesses of large animal models is critical for trauma and hemorrhage research. Each model is unique and should be chosen based on how well it aligns with the specific scientific objectives of the study. By strategically considering each model's advantages and limitations, we can enhance our understanding of trauma and hemorrhage pathophysiology and further advance the development of effective treatments.

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“…Massive haemorrhage has previously been studied in swine models [20-24], but only a few have studied the effect of hypoperfusion in combination with soft tissue injury and fractures in the initial phase prior to fluid resuscitation [25,26]. White et al studied the effect on conventional coagulation parameters as well as thrombelastography using TEG, in a model of injured and haemorrhaged swine.…”

Section: Discussionmentioning

confidence: 99%

Changes in fibrinogen availability and utilization in an animal model of traumatic coagulopathy

Hagemo

Jørgensen

Ostrowski

et al. 2013

Scand J Trauma Resusc Emerg Med

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BackgroundImpaired haemostasis following shock and tissue trauma is frequently detected in the trauma setting. These changes occur early, and are associated with increased mortality. The mechanism behind trauma-induced coagulopathy (TIC) is not clear. Several studies highlight the crucial role of fibrinogen in posttraumatic haemorrhage. This study explores the coagulation changes in a swine model of early TIC, with emphasis on fibrinogen levels and utilization of fibrinogen.MethodsA total of 18 landrace pigs were anaesthetized and divided into four groups. The Trauma-Shock group (TS) were inflicted bilateral blast femoral fractures with concomitant soft tissue injury by a high-energy rifle shot to both hind legs, followed by controlled exsanguination. The Shock group (S) was exposed to shock by exsanguination, whereas a third group was exposed to trauma only (T). A fourth group (C) served as control. Physiological data, haematological measurements, blood gas analyses and conventional coagulation assays were recorded at baseline and repeatedly over 60 minutes. Thrombelastometry were performed by means of the tissue factor activated ExTEM assay and the platelet inhibiting FibTEM assay. Data were statistically analysed by repeated measurements analyses method.ResultsA significant reduction of fibrinogen concentration was observed in both the TS and S groups. INR increased significantly in the S group and differed significantly from the TS group. Maximum clot firmness (MCF) of the ExTEM assay was significantly reduced over time in both TS and S groups. In the FibTEM assay a significant shortening of the clotting time and an increase in MCF was observed in the TS group compared to the S group.ConclusionDespite a reduction in clotting capability measured by ExTEM MCF and a reduced fibrinogen concentration, extensive tissue trauma may induce an increased fibrin based clotting activity that attenuates the hypocoagulable tendency in exsanguinated animals.

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Systemic central venous oxygen saturation is associated with clot strength during traumatic hemorrhagic shock: A preclinical observational model

Cited by 7 publications

References 47 publications

Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid

Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid

The Use of Large Animal Models in Trauma and Bleeding Studies

Changes in fibrinogen availability and utilization in an animal model of traumatic coagulopathy

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