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1.
J Trauma Acute Care Surg ; 84(1): 89-96, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28930945

RESUMO

BACKGROUND: Traumatic brain injury causes a disruption of the vascular endothelial glycocalyx layer that is associated with an overactivation of the sympathoadrenal system. We hypothesized that early and unselective beta-blockade with propranolol alone or in combination with the alfa2-agonist clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma. METHODS: We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal motor function. RESULTS: We found no difference in brain water content (mean ± SD) between propranolol (80.8 ± 0.3%; 95% confidence interval [CI], 80.7-81.0) and vehicle (81.1 ± 0.6%; 95% CI, 80.8-81.4) (p = 0.668) or between propranolol/clonidine (80.8 ± 0.3%; 95% CI, 80.7-81.0) and vehicle (p = 0.555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels. CONCLUSION: This study does not provide any support for unselective beta-blockade with propranolol or the combination of propranolol and the alfa2-agonist clonidine on brain water content. The novel finding of an increase in plasma concentrations of epinephrine and syndecan-1 after propranolol treatment in traumatic brain injury is of unclear significance and should be investigated further.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Edema Encefálico/metabolismo , Lesões Encefálicas Traumáticas/complicações , Clonidina/farmacologia , Propranolol/farmacologia , Animais , Edema Encefálico/etiologia , Edema Encefálico/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Permeabilidade Capilar/efeitos dos fármacos , Modelos Animais de Doenças , Glicocálix/efeitos dos fármacos , Glicocálix/metabolismo , Glicocálix/patologia , Masculino , Ratos , Ratos Sprague-Dawley
2.
J Neurotrauma ; 34(5): 1054-1062, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27626366

RESUMO

Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG® [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage. After fluid percussion brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for 51Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB permeability. Plasma osmolality and oncotic pressures were highest in FFP and OCTA resuscitated, and osmolality was further highest in OCTA versus FFP (p = 0.027). In addition, syndecan-1 was highest in FFP and OCTA resuscitated (p = 0.010). These results suggest that pooled solvent-detergent (SD)-treated plasma attenuates the post-traumatic increase in brain water content, and that this effect may, in part, be explained by a high crystalloid and colloid osmotic pressure in SD-treated plasma.


Assuntos
Lesões Encefálicas Traumáticas/terapia , Encéfalo/metabolismo , Plasma , Ressuscitação/métodos , Choque Hemorrágico/terapia , Água/metabolismo , Animais , Detergentes , Modelos Animais de Doenças , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Solventes
3.
J Neurotrauma ; 30(4): 301-6, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23134525

RESUMO

It remains to be debated whether traumatic brain injury (TBI) induces a different coagulopathy than does non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy, and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients was sampled (median of 68 min [IQR 48-88] post-injury) upon admission to our trauma center. Plasma/serum were retrospectively analyzed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue factor pathway inhibitor, antithrombin, prothrombin fragment 1+2, thrombin/antithrombin complex, von Willebrand factor, factor XIII, d-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1), immunology (interleukin [IL]6), endothelial cell/glycocalyx damage (soluble thrombomodulin, syndecan-1), and vasculogenesis (angiopoietin-1, -2). Patients were stratified according to: (1) isolated severe head/neck injuries (Abbreviated injury score [AIS]-head/neck ≥ 3, AIS-other<3) (isoTBI); (2) severe head/neck and extracranial injuries (AIS-head/neck ≥ 3, AIS-other>3) (sTBI+other); and (3) injuries without significant head/neck injuries (AIS-head/neck<3, including all AIS-other scores) (non-TBI). Twenty-three patients presented with isoTBI, 15 with sTBI+other and 42 with non-TBI. Acute coagulopathy of trauma shock, defined as activated partial thromboplastin time (APTT) and/or international normalized ratio (INR)>35 sec and>1.2, was found in 13%, 47%, and 5%, respectively (p=0.000). sTBI+other had significantly higher plasma levels of adrenaline, noradrenaline, annexin V, d-dimer, IL-6, syndecan-1, soluble thrombomodulin, and reduced protein C and factor XIII levels (all p<0.05). No significant biomarker differences were found between isoTBI and non-TBI patients. Injury severity scale (ISS) rather than the presence or absence of head/neck injuries determined the hemostatic and biomarker response to the injury. The coagulopathy identified thus reflected the severity of injury rather than its localization.


Assuntos
Biomarcadores/sangue , Lesões Encefálicas/sangue , Lesões Encefálicas/complicações , Coagulação Intravascular Disseminada/sangue , Adulto , Idoso , Testes de Coagulação Sanguínea , Lesões Encefálicas/patologia , Coagulação Intravascular Disseminada/etiologia , Endotélio Vascular/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade
4.
Clin Appl Thromb Hemost ; 18(6): 638-44, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22297558

RESUMO

BACKGROUND: Rapid identification of clinically relevant coagulopathies in, acute coagulopathy of trauma shock (ACOTS) has led to the development of faster point-of-care viscoelastic whole-blood-based tests like rapid thrombelastography (RapidTEG). The sensitivity of RapidTEG to detect hyperfibrinolysis, as compared to standard KaolinTEG, is unknown. To investigate this, the ability of RapidTEG, KaolinTEG, and functional fibrinogenTEG (FFTEG) to detect tPA-induced (tissue plasminogen activator) lysis in whole blood from healthy individuals was investigated. Our hypothesis was that the initial powerful clot formation in the RapidTEG assay would reduce the sensitivity as compared to the normally used KaolinTEG assay. We also evaluated the FFTEG assay. METHODS: In vitro comparison of the sensitivity of RapidTEG, KaolinTEG, and FFTEG to 1.8 nmol/L tPA in citrated whole blood (299 ± 23 ng/mL plasma) induced hyperfibrinolysis in 10 healthy individuals and duplicate titration of the tPA whole blood (WB) concentration from 0.09 to 7.2 nmol/L (14-1144 ng/mL plasma) in 1 healthy donor. RESULTS: At 1.8 nmol/L tPA, KaolinTEG, RapidTEG, and FFTEG all detected fibrinolysis but with different sensitivities. In the titration study, KaolinTEG and FFTEG displayed a continuous dose-response association and RapidTEG also displayed a dose-dependent response but only for higher levels of tPA, thus yielding a smaller "dose-sensitive range" compared to KaolinTEG and FFTEG. CONCLUSION: This pilot study demonstrated that KaolinTEG, RapidTEG, and FFTEG all were able to detect lysis at 1.8 nmol/L tPA but with a difference in sensitivity. Furthermore, KaolinTEG and FFTEG showed a continuous dose dependence related to the tPA concentration, whereas RapidTEG only detected lysis at higher tPA concentrations.


Assuntos
Hemólise , Transtornos Hemorrágicos/sangue , Tromboelastografia/métodos , Ativador de Plasminogênio Tecidual/metabolismo , Adulto , Feminino , Humanos , Masculino , Projetos Piloto , Inibidor 1 de Ativador de Plasminogênio/sangue , Inibidor 1 de Ativador de Plasminogênio/deficiência
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