INCREASED PLATELET MITOCHONDRIAL FUNCTION CORRELATES WITH CLOT STRENGTH IN A RODENT FRACTURE MODEL.
Journal
The journal of trauma and acute care surgery
ISSN: 2163-0763
Titre abrégé: J Trauma Acute Care Surg
Pays: United States
ID NLM: 101570622
Informations de publication
Date de publication:
13 Nov 2023
13 Nov 2023
Historique:
medline:
14
11
2023
pubmed:
14
11
2023
entrez:
14
11
2023
Statut:
aheadofprint
Résumé
Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging due to a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function, but has not yet been correlated with functional coagulation studies. Wistar rats underwent anesthesia and either immediate sacrifice for baseline values [n = 6] or (1) bilateral hindlimb orthopedic injury [n = 12], versus (2) sham anesthesia [n = 12] with terminal phlebotomy/hepatectomy after 24 hours. High resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex-I and Complex-II driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate. Citrated native TEG maximal amplitude (MA) was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared to sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol/s*108 cells, p = 0.045), with similar trends in mitochondrial leak rate (p = 0.19) when compared to sham animals. Overall, platelet basal respiration significantly correlated with TEG-MA (r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex-I driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e-/min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen. Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.
Sections du résumé
BACKGROUND
BACKGROUND
Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging due to a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function, but has not yet been correlated with functional coagulation studies.
METHODS
METHODS
Wistar rats underwent anesthesia and either immediate sacrifice for baseline values [n = 6] or (1) bilateral hindlimb orthopedic injury [n = 12], versus (2) sham anesthesia [n = 12] with terminal phlebotomy/hepatectomy after 24 hours. High resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex-I and Complex-II driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate.
RESULTS
RESULTS
Citrated native TEG maximal amplitude (MA) was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared to sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol/s*108 cells, p = 0.045), with similar trends in mitochondrial leak rate (p = 0.19) when compared to sham animals. Overall, platelet basal respiration significantly correlated with TEG-MA (r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex-I driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e-/min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen.
CONCLUSIONS
CONCLUSIONS
Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.
Identifiants
pubmed: 37962216
doi: 10.1097/TA.0000000000004204
pii: 01586154-990000000-00565
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
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