Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.833
Filtrar
1.
PLoS One ; 15(10): e0239222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33001983

RESUMO

BACKGROUND: To prevent bio-accumulation of low molecular weight heparins (LMWHs) in patients with decreased kidney function, dosage reduction and anti-Xa monitoring has been suggested. The aim of this study was to investigate the effect of pre-emptive dosage reduction of LMWH on anti-Xa levels. Furthermore, we investigated the association between anti-Xa levels and bleeding, thrombotic events and mortality. METHODS: In this single center study, we followed 499 patients with decreased renal function in whom anti-Xa levels were measured. We observed how many patients had anti-Xa levels that fell within the reference range, with a standard protocol of a pre-emptive dosage reduction of LMWH (25% reduction in patients with an estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73m2 and a reduction of 50% in patients with an eGFR below the 30 ml/min/1.73m2). Furthermore, Cox proportional hazard analyses were used to estimate hazard ratios to investigate the association between anti-Xa levels and major bleeding, thrombotic events and mortality within three months of follow-up. RESULTS: In a cohort of 499 patients (445 dalteparin and 54 nadroparin users), a pre-emptive dosage reduction of LMWH led to adequate levels of anti-Xa in only 19% of the patients (12% for the dalteparin users and 50% for nadroparin users). We did not find an association between anti-Xa levels and bleeding, thrombosis or mortality. CONCLUSION: Pre-emptive dosage reduction of LMWH leads to low anti-Xa levels in a large proportion, but this was not associated with bleeding, thrombosis or mortality.


Assuntos
Inibidores do Fator Xa/metabolismo , Heparina de Baixo Peso Molecular/efeitos adversos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Idoso , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Hemorragia/fisiopatologia , Heparina de Baixo Peso Molecular/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Trombose/fisiopatologia
2.
Nat Commun ; 11(1): 5209, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060602

RESUMO

Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Here, we aim to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of T2 SCI, we assess LV end-systolic elastance (contractility) via invasive pressure-volume catheterization, monitor intraparenchymal SCO2 and SCBF with fiberoptic oxygen sensors and laser-Doppler flowmetry, respectively, and quantify spinal cord metabolites with microdialysis. We demonstrate that high-thoracic SCI acutely impairs cardiac contractility and substantially reduces SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that augmenting LV contractility with the ß-agonist dobutamine increases SCO2 and SCBF more effectively than vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Finally, in pigs with T2 SCI survived for 12 weeks post-injury, we confirm that acute hemodynamic management with dobutamine appears to preserve cardiac function and improve hemodynamic outcomes in the chronic setting. Our data support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.


Assuntos
Coração/fisiopatologia , Hemodinâmica/fisiologia , Hemorragia/fisiopatologia , Fenômenos Fisiológicos Respiratórios , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Modelos Animais de Doenças , Dobutamina/farmacologia , Feminino , Fluxometria por Laser-Doppler , Chaperonas Moleculares/metabolismo , Norepinefrina/farmacologia , Fluxo Sanguíneo Regional/fisiologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Suínos , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologia
3.
J Trauma Acute Care Surg ; 89(2): 320-328, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740640

RESUMO

BACKGROUND: Noncompressible hemorrhage remains a high-mortality injury, and aortic balloon occlusion poses limitations in terms of distal ischemic injury. Our hypothesis was that a retrievable Rescue stent would confer improved outcome over aortic balloon occlusion. METHODS: A three-tier, retrievable stent graft was laser welded from nitinol and polytetrafluoroethylene to provide rapid thoracic and abdominal coverage with an interval bare metal segment to preserve visceral flow. Anesthetized swine had injury of the thoracic or abdominal aorta followed by balloon occlusion or a Rescue stent. A 1-hour long damage-control phase with blood repletion was used to simulate the prolonged interval between injury and repair, especially in the battlefield setting. Following the damage-control phase, the balloon or stent were retrieved followed by vascular repair and recovery to 48 hours. Animals were compared in terms of hemodynamics, blood loss, neurophysiologic spinal cord ischemia, ischemic organ injury, and survival. RESULTS: Despite antegrade hemorrhage control, balloon occlusion averaged 3.5 L of retrograde hemorrhage, loss of visceral perfusion, and permanent spinal cord ischemia by neurophysiology in six of seven animals. After permanent repair, all balloon occlusion animals died with only a single short term (5 hours) survivor. Conversely, Rescue stent animals revealed rapid hemorrhage control (in under 2 minutes) whether the injury was thoracic or abdominal with improved hemodynamics, preserved visceral flow, reduced spinal cord ischemia, negligible histologic organ injury and survival to end of study in all abdominal injured animals (n = 6) and four of six thoracic injured animals, with two deaths related to arrhythmia. CONCLUSION: Compared with aortic balloon occlusion, a Rescue stent offers superior hemorrhage control and survival by virtue of reduced ischemic injury and direct control of the hemorrhagic injury. The Rescue stent may become a useful tool for damage control, especially on the battlefield where definitive repair presents logistical challenges.


Assuntos
Aorta/lesões , Aorta/cirurgia , Oclusão com Balão , Procedimentos Endovasculares , Hemorragia/cirurgia , Stents , Animais , Hemodinâmica , Hemorragia/etiologia , Hemorragia/fisiopatologia , Hemorragia/prevenção & controle , Isquemia/etiologia , Isquemia/prevenção & controle , Modelos Animais , Medula Espinal/irrigação sanguínea , Suínos , Resultado do Tratamento , Vísceras/irrigação sanguínea , Lesões Relacionadas à Guerra/complicações , Lesões Relacionadas à Guerra/cirurgia
4.
J Stroke Cerebrovasc Dis ; 29(9): 105063, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807468

RESUMO

BACKGROUND AND OBJECTIVE: After cerebral hemorrhage, cognitive functions and activities of daily living (ADL) are affected by various factors, including hematoma volume and patient age. In the present study, we investigated the effect of age and hematoma volume on cognitive functions and on ADL. METHODS: The sample comprised 274 patients (183 men and 91 women; mean age 58.2 ± 12.5 years) with putaminal hemorrhage who were hospitalized in a convalescent rehabilitation ward. Hematoma volume was estimated from computed tomography imaging at stroke onset. Cognitive functions were evaluated using Raven's Colored Progressive Matrices test (RCPM) and the Mini-Mental State Examination (MMSE) at hospital admission, while ADL score was assessed at discharge using the Functional Independence Measure motor subscale (FIM-M). In the present study, we classified the patients into six groups according to whether they were non-elderly or elderly (cutoff age, 60 years) and whether their hematoma was small, medium, or large (cutoff volumes, 20 and 40 mL, respectively). Subsequently, the scores on the RCPM, MMSE, and FIM-M were compared among the groups. RESULTS: In both age groups, patients with a larger hematoma volume had lower RCPM and MMSE scores. Patients <60 years old exhibited different trends in their RCPM and MMSE scores, such that the RCPM score showed a step-wise decrease according to hematoma volume, while a difference in the MMSE score was only observed at the 20 mL boundary. Most of the younger patients (<60 years of age) attained high FIM-M scores at discharge, as long as their hematoma volume was either medium or small (<40 mL). This age group had higher RCPM scores on admission, which may have contributed to their higher FIM-M scores on discharge. CONCLUSIONS: In the present study, we demonstrated that advancing age increases the effect of hematoma volume on RCPM and MMSE scores and identified differences in the effects observed on these two scores. Thus, it may be important to use the RCPM alongside the MMSE for patient assessment.


Assuntos
Atividades Cotidianas , Transtornos Cognitivos/etiologia , Cognição , Envelhecimento Cognitivo , Hemorragia/diagnóstico por imagem , Hemorragia Putaminal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Fatores Etários , Idoso , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Feminino , Hemorragia/complicações , Hemorragia/fisiopatologia , Hemorragia/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Prognóstico , Hemorragia Putaminal/complicações , Hemorragia Putaminal/fisiopatologia , Hemorragia Putaminal/psicologia , Fatores de Risco
5.
Toxicol Lett ; 333: 211-221, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32841740

RESUMO

Bothrops (lance-head pit vipers) venoms are rich in weaponised metalloprotease enzymes (SVMP). These toxic enzymes are structurally diverse and functionally versatile. Potent coagulotoxicity is particularly important for prey capture (via stroke-induction) and relevant to human clinical cases (due to consumption of clotting factors including the critical depletion of fibrinogen). In this study, three distinct isoforms of P-III class SVMPs (IC, IIB and IIC), isolated from Bothrops neuwiedi venom, were evaluated for their differential capacities to affect hemostasis of prey and human plasma. Furthermore, we tested the relative antivenom neutralisation of effects upon human plasma. The toxic enzymes displayed differential procoagulant potency between plasma types, and clinically relevant antivenom efficacy variations were observed. Of particular importance was the confirmation the antivenom performed better against prothrombin activating toxins than Factor X activating toxins, which is likely due to the greater prevalence of the former in the immunising venoms used for antivenom production. This is clinically relevant as the enzymes displayed differential potency in this regard, with one (IC) in particular being extremely potent in activating Factor X and thus was correspondingly poorly neutralised. This study broadens the current understanding about the adaptive role of the SVMPs, as well as highlights how the functional diversity of SVMP isoforms can influence clinical outcomes. Key Contribution: Our findings shed light upon the hemorrhagic and coagulotoxic effects of three SVMPs of the P-III class, as well as the coagulotoxic effects of SVMPs on human, avian and amphibian plasmas. Antivenom neutralised prothrombin-activating isoforms better than Factor X activating isoforms.


Assuntos
Antivenenos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/prevenção & controle , Metaloproteases/toxicidade , Venenos de Serpentes/enzimologia , Animais , Bothrops , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/fisiopatologia , Humanos , Microscopia Intravital , Masculino , Metaloproteases/química , Camundongos , Microcirculação/efeitos dos fármacos , Microvasos/diagnóstico por imagem , Microvasos/efeitos dos fármacos , Microvasos/patologia , Isoformas de Proteínas
6.
Vasc Endovascular Surg ; 54(8): 665-669, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32720585

RESUMO

PURPOSE: To evaluate the efficacy, safety, and feasibility of transradial approach (TRA) for endovascular management of traumatic bleeding. MATERIALS AND METHODS: A retrospective review was performed at a single level 1 trauma institution from August 2018 to July 2019. Patients presented to the interventional radiology department who were intended to be treating using TRA for the management of trauma-induced bleeding were selected. Demographics, indication for embolization, embolization site, preprocedural labs, hemodynamic stability, technical success, and complications were recorded. RESULTS: Transradial approach was attempted in 29 (74.4%) of the 39 patients identified by operators who prefer TRA. Four patients received treatment using TRA on 2 separate occasions, for a total of 33 procedures completed with a technical success of 97% (32/33). Transradial approach was safely completed in 9 patients (27.3%) with preprocedural hemodynamically unstable status. For the 10 patients who received treatment via a transfemoral approach (TFA), traumatic disfiguration of the left upper extremity, preexisting arterial lines placed by the trauma team, and external iliac artery injuries requiring covered stent placement were the most common indications for TFA over TRA. There were no procedural or access site-related complications. CONCLUSION: Transradial approach for the endovascular management of bleeding in a trauma setting is safe and effective with a high technical success rate and no complications.


Assuntos
Cateterismo Periférico , Embolização Terapêutica , Procedimentos Endovasculares , Hemorragia/terapia , Artéria Radial , Lesões do Sistema Vascular/terapia , Adulto , Idoso , Cateterismo Periférico/efeitos adversos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Estudos de Viabilidade , Feminino , Hemodinâmica , Hemorragia/diagnóstico , Hemorragia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , New Jersey , Punções , Artéria Radial/diagnóstico por imagem , Radiografia Intervencionista , Estudos Retrospectivos , Stents , Centros de Traumatologia , Resultado do Tratamento , Serviços Urbanos de Saúde , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/fisiopatologia , Adulto Jovem
7.
PLoS One ; 15(6): e0234407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511276

RESUMO

Testisin (encoded by PRSS21) is a membrane anchored serine protease, which is tethered to the cell surface via a glycosylphosphatidylinositol (GPI)-anchor. While testisin is found in abundance in spermatozoa, it is also expressed in microvascular endothelial cells where its function is unknown. Here we identify testisin as a novel regulator of physiological hormone-induced angiogenesis and microvascular endothelial permeability. Using a murine model of rapid physiological angiogenesis during corpus luteal development in the ovary, we found that mice genetically deficient in testisin (Prss21-/-) show a substantially increased incidence of hemorrhages which are significantly more severe than in littermate control Prss21+/+ mice. This phenotype was associated with increased vascular leakiness, demonstrated by a greater accumulation of extravasated Evans blue dye in Prss21-/- ovaries. Live cell imaging of in vitro cultured microvascular endothelial cells depleted of testisin by siRNA knockdown revealed that loss of testisin markedly impaired reorganization and tubule-like formation on Matrigel basement membranes. Moreover testisin siRNA knockdown increased the paracellular permeability to FITC-albumin across endothelial cell monolayers, which was associated with decreased expression of the adherens junction protein VE-cadherin and increased levels of phospho(Tyr658)-VE-cadherin, without affecting the levels of the tight junction proteins occludin and claudin-5, or ZO-1. Decreased expression of VE-cadherin in the neovasculature of Prss21-/- ovaries was also observed without marked differences in endothelial cell content, vascular claudin-5 expression or pericyte recruitment. Together, these data identify testisin as a novel regulator of VE-cadherin adhesions during angiogenesis and indicate a potential new target for regulating neovascular integrity and associated pathologies.


Assuntos
Permeabilidade Capilar/fisiologia , Corpo Lúteo/irrigação sanguínea , Neovascularização Fisiológica , Serina Endopeptidases/deficiência , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Permeabilidade Capilar/genética , Células Cultivadas , Corpo Lúteo/patologia , Corpo Lúteo/fisiopatologia , Feminino , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/deficiência , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/fisiologia , Técnicas de Silenciamento de Genes , Hemorragia/etiologia , Hemorragia/genética , Hemorragia/fisiopatologia , Humanos , Luteinização/genética , Luteinização/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Fisiológica/genética , Fenótipo , Serina Endopeptidases/genética , Serina Endopeptidases/fisiologia
8.
Anesth Analg ; 130(5): 1176-1187, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32287125

RESUMO

BACKGROUND: Individualized hemodynamic monitoring approaches are not well validated. Thus, we evaluated the discriminative performance improvement that might occur when moving from noninvasive monitoring (NIM) to invasive monitoring and with increasing levels of featurization associated with increasing sampling frequency and referencing to a stable baseline to identify bleeding during surgery in a porcine model. METHODS: We collected physiologic waveform (WF) data (250 Hz) from NIM, central venous (CVC), arterial (ART), and pulmonary arterial (PAC) catheters, plus mixed venous O2 saturation and cardiac output from 38 anesthetized Yorkshire pigs bled at 20 mL/min until a mean arterial pressure of 30 mm Hg following a 30-minute baseline period. Prebleed physiologic data defined a personal stable baseline for each subject independently. Nested models were evaluated using simple hemodynamic metrics (SM) averaged over 20-second windows and sampled every minute, beat to beat (B2B), and WF using Random Forest Classification models to identify bleeding with or without normalization to personal stable baseline, using a leave-one-pig-out cross-validation to minimize model overfitting. Model hyperparameters were tuned to detect stable or bleeding states. Bleeding models were compared use both each subject's personal baseline and a grouped-average (universal) baseline. Timeliness of bleed onset detection was evaluated by comparing the tradeoff between a low false-positive rate (FPR) and shortest time to bleed detection. Predictive performance was evaluated using a variant of the receiver operating characteristic focusing on minimizing FPR and false-negative rates (FNR) for true-positive and true-negative rates, respectively. RESULTS: In general, referencing models to a personal baseline resulted in better bleed detection performance for all catheters than using universal baselined data. Increasing granularity from SM to B2B and WF progressively improved bleeding detection. All invasive monitoring outperformed NIM for both time to bleeding detection and low FPR and FNR. In that regard, when referenced to personal baseline with SM analysis, PAC and ART + PAC performed best; for B2B CVC, PAC and ART + PAC performed best; and for WF PAC, CVC, ART + CVC, and ART + PAC performed equally well and better than other monitoring approaches. Without personal baseline, NIM performed poorly at all levels, while all catheters performed similarly for SM, with B2B PAC and ART + PAC performing the best, and for WF PAC, ART, ART + CVC, and ART + PAC performed equally well and better than the other monitoring approaches. CONCLUSIONS: Increasing hemodynamic monitoring featurization by increasing sampling frequency and referencing to personal baseline markedly improves the ability of invasive monitoring to detect bleed.


Assuntos
Análise de Dados , Monitorização Hemodinâmica/métodos , Hemodinâmica/fisiologia , Hemorragia/diagnóstico , Hemorragia/fisiopatologia , Animais , Pressão Arterial/fisiologia , Débito Cardíaco , Feminino , Monitorização Fisiológica/métodos , Suínos
9.
Ulus Travma Acil Cerrahi Derg ; 26(2): 163-170, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32185761

RESUMO

BACKGROUND: Different pharmacological agents are developed to control bleeding. However, it is critical for these agents to induce thrombin formation and have an effect on vasoconstriction, coagulation, and scaffold. In this study, we aimed to demonstrate the agents' ability to stop bleeding properties on minor and major open bleedings after skin clefts, extracorporal injuries, traumatic cuts, spontaneous or surgical intervention besides scaffold properties. For this purpose, a new and authentic hemostatic agent, processed diatomite (PD) and the most preferred chitosan in the medical area were used to test blood stopping and scaffold effects in a rat femoral bleeding model. The samples were examined by scanning electron microscopy (SEM), and the results on blood stopping were shared. METHODS: The current experimental study was conducted on rats. The effects of hemostatic agents on our femoral bleeding model were determined. In this study, 22 male Wistar albino rats weighing 158-215 g, were used. The rats were assigned randomly to three groups: control group (n=6), chitosan group (n=8), and PD group (n=8). Bleeding time, scaffold formation, weight differences, histopathological effect and scanning electron microscope (SEM) analyses were performed. RESULTS: In our experimental model, weight loss was 5.0±1.3 g for the control group, 2.9±1.1 g for the chitosan group, and 2.7±1.0 g for the PD group, respectively. When weighed before and after the experiment, there was a significant change in weights of rats in chitosan, and PD groups regarding scaffold formation: it was complete for six rats (75%) and weak for two (25%) rats in chitosan group; however, it was complete for seven rats (87.5%) and weak for one (12.5%) rat in the PD group. Scaffold formation was significant for the chitosan and PD groups versus the control group (p=0.002). CONCLUSION: In our study, the scaffold formed by PD exerts appropriate porousness and contributes to fibrin formation and prevent re-bleeding. PD had a strong and significant scaffold effect. The effectiveness of PD to stop bleeding was equal to chitosan. Besides being natural, hemostatic agents should not induce cellular damage. We histopathologically demonstrated that PD was harmless for the natural structure of cells and vessels in the femoral site.


Assuntos
Hemorragia/fisiopatologia , Hemostasia/efeitos dos fármacos , Hemostáticos/farmacologia , Animais , Quitosana/farmacologia , Terra de Diatomáceas/farmacologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
10.
Blood Coagul Fibrinolysis ; 31(3): 198-206, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32004201

RESUMO

: The effects of rapid hemorrhage on coagulopathy have been reported. However, the effects of different hemorrhage speeds on the blood coagulation/fibrinolysis system have not been investigated. This study aimed to compare different hemorrhage speeds for clarifying their effects on the coagulation/fibrinolysis system and circulation disorders in rats. Male Sprague-Dawley rats (301-396 g) were randomly assigned to five groups depending on hemorrhage speed and length of procedure: first, rapid (1.4 ml/min, 30-min bleeding); second, rapid-L (1.4 ml/min, 30-min bleeding and observation until 6 h); third, slow (0.1 ml/min, intermittently, 6-h bleeding); fourth, control (30-min observation); and fifth, control-L (6-h observation). Hemorrhage was induced by withdrawing blood until 40% of the estimated blood volume from the femoral artery. We measured vital signs, hematology, general chemistry, blood gas status, coagulation parameters, fibrinolytic markers [tissue-type plasminogen activator and plasminogen activator inhibitor one (PAI-1)], vascular endothelial damage (syndecan-1), and liver PAI-1 mRNA expression. Rapid hemorrhage induced elevation of lactate and syndecan-1 levels and prolonged prothrombin time and activated partial thromboplastin time in the rapid group. In contrast, slow hemorrhage did not induce these changes. Hemorrhage speed had no effect on plasma tissue-type plasminogen activator and hematology. Plasma PAI-1 levels were significantly increased in the rapid-L group, while liver PAI-1 mRNA levels were increased in the slow group. This study shows changes in the circulatory and fibrinolysis systems, depending on the hemorrhage speed. Hemorrhage might promote production of PAI-1, while tissue hypoxia due to rapid hemorrhage might promote release of PAI-1.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hemorragia/fisiopatologia , Animais , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
11.
Mil Med ; 185(Suppl 1): 77-81, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-32074299

RESUMO

INTRODUCTION: Acute compartment syndrome (ACS) is a well-recognized and common emergency. Undiagnosed ACS leads to muscle necrosis, limb contracture, intractable pain, and may even result in amputation. METHODS: Three devices (Synthes, Stryker, and MY01) were compared in a pre-clinical rat abdominal compartment syndrome simulation. Simultaneous measurements of intracompartmental pressures allowed concurrent comparison among all devices. RESULTS: Large variations from the reference values are seen with the Synthes and Stryker devices. Variances are large in these two devices even under ideal conditions. The MY01 device was the truest indicator of reference pressure in this ACS model (over 600% more accurate). CONCLUSIONS: The MY01 device was the most accurate device in tracking pressure changes in this rat model of abdominal compartment syndrome.


Assuntos
Síndromes Compartimentais/classificação , Desenho de Equipamento/normas , Pressão , Pesos e Medidas/normas , Animais , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/fisiopatologia , Modelos Animais de Doenças , Desenho de Equipamento/estatística & dados numéricos , Hemorragia/fisiopatologia , Hemorragia/cirurgia , Ratos Sprague-Dawley , Pesos e Medidas/instrumentação , Ferimentos e Lesões/complicações
12.
Mil Med ; 185(Suppl 1): 96-102, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-32074370

RESUMO

INTRODUCTION: Commercially available junctional tourniquets (JTQs) have several drawbacks. We developed a low-cost, compact, easy to apply JTQ. The aim of this study was to assess the tourniquets' safety and efficacy in a swine model of controlled hemorrhage. MATERIALS AND METHODS: Five pigs were subjected to controlled bleeding of 35% of their blood volume. Subsequently, the JTQ was applied to the inguinal area for 180 minutes. Afterwards, the tourniquet was removed for additional 60 minutes of follow up. During the study, blood flow to both hind limbs and blood samples for tissue damage markers were repeatedly assessed. Following sacrifice, injury to both inguinal areas was evaluated microscopically and macroscopically. RESULTS: Angiography demonstrated complete occlusion of femoral artery flow, which was restored following removal of the tourniquet. No gross signs of tissue damage were noticed. Histological analysis revealed mild necrosis and infiltration of inflammatory cells. Blood tests showed a mild increase in potassium and lactic acid levels throughout the protocol. CONCLUSIONS: The tourniquet achieved effective arterial occlusion with minimal tissue damage, similar to reports of other JTQs. Subjected to further human trials, the tourniquet might be a suitable candidate for widespread frontline deployment because of its versatility, compactness, and affordable design.


Assuntos
Hemorragia/cirurgia , Choque Hemorrágico/cirurgia , Torniquetes/normas , Animais , Modelos Animais de Doenças , Hemodinâmica/fisiologia , Hemorragia/fisiopatologia , Membro Posterior/irrigação sanguínea , Membro Posterior/lesões , Membro Posterior/fisiopatologia , Segurança do Paciente/normas , Segurança do Paciente/estatística & dados numéricos , Choque Hemorrágico/prevenção & controle , Suínos/lesões , Suínos/fisiologia , Torniquetes/estatística & dados numéricos , Ultrassonografia Doppler/métodos
13.
Artigo em Inglês | MEDLINE | ID: mdl-32101016

RESUMO

Acute lung injury is a major complication of hemorrhagic shock and the required resuscitation with large volumes of crystalloid fluids and blood products. We previously identified a role of macrophage-derived chemokine (CCL22/MDC) pulmonary inflammation following hemorrhage and resuscitation. However, further details regarding the induction of CCL22/MDC and its precise role in pulmonary inflammation after trauma remain unknown. In the current study we used in vitro experiments with a murine alveolar macrophage cell line, as well as an in vivo mouse model of hemorrhage and resuscitation, to identify key regulators in CCL22/MDC production. We show that trauma induces expression of IFNγ, which leads to production of CCL22/MDC through a signaling mechanism involving p38 MAPK, NF-κB, JAK, and STAT-1. IFNγ also activates TNFα production by alveolar macrophages, potentiating CCL22/MDC production via an autocrine mechanism. Neutralization of IFNγ or TNFα with specific antibodies reduced histological signs of pulmonary injury after hemorrhage and reduced inflammatory cell infiltration into the lungs.


Assuntos
Quimiocina CCL2/genética , Hemorragia/genética , Hipotensão/genética , Interferon gama/genética , Macrófagos Alveolares/metabolismo , Pneumonia/genética , Fator de Necrose Tumoral alfa/genética , Animais , Anticorpos Neutralizantes/farmacologia , Comunicação Autócrina/genética , Linhagem Celular , Quimiocina CCL2/metabolismo , Regulação da Expressão Gênica , Hemorragia/metabolismo , Hemorragia/fisiopatologia , Humanos , Hipotensão/metabolismo , Hipotensão/fisiopatologia , Interferon gama/antagonistas & inibidores , Interferon gama/metabolismo , Janus Quinases/genética , Janus Quinases/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Pneumonia/metabolismo , Pneumonia/fisiopatologia , Ressuscitação/métodos , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Arterioscler Thromb Vasc Biol ; 40(4): 901-913, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32102568

RESUMO

OBJECTIVE: Cardiac myosin (CM) is structurally similar to skeletal muscle myosin, which has procoagulant activity. Here, we evaluated CM's ex vivo, in vivo, and in vitro activities related to hemostasis and thrombosis. Approach and Results: Perfusion of fresh human blood over CM-coated surfaces caused thrombus formation and fibrin deposition. Addition of CM to blood passing over collagen-coated surfaces enhanced fibrin formation. In a murine ischemia/reperfusion injury model, exogenous CM, when administered intravenously, augmented myocardial infarction and troponin I release. In hemophilia A mice, intravenously administered CM reduced tail-cut-initiated bleeding. These data provide proof of concept for CM's in vivo procoagulant properties. In vitro studies clarified some mechanisms for CM's procoagulant properties. Thrombin generation assays showed that CM, like skeletal muscle myosin, enhanced thrombin generation in human platelet-rich and platelet-poor plasmas and also in mixtures of purified factors Xa, Va, and prothrombin. Binding studies showed that CM, like skeletal muscle myosin, directly binds factor Xa, supporting the concept that the CM surface is a site for prothrombinase assembly. In tPA (tissue-type plasminogen activator)-induced plasma clot lysis assays, CM was antifibrinolytic due to robust CM-dependent thrombin generation that enhanced activation of TAFI (thrombin activatable fibrinolysis inhibitor). CONCLUSIONS: CM in vitro is procoagulant and prothrombotic. CM in vivo can augment myocardial damage and can be prohemostatic in the presence of bleeding. CM's procoagulant and antifibrinolytic activities likely involve, at least in part, its ability to bind factor Xa and enhance thrombin generation. Future work is needed to clarify CM's pathophysiology and its mechanistic influences on hemostasis or thrombosis.


Assuntos
Coagulação Sanguínea , Miosinas Cardíacas/metabolismo , Hemostasia , Trombina/biossíntese , Trombose/fisiopatologia , Animais , Plaquetas/metabolismo , Miosinas Cardíacas/fisiologia , Modelos Animais de Doenças , Fator Va/metabolismo , Fator Xa/metabolismo , Hemorragia/fisiopatologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Protrombina/metabolismo
15.
J Vis Exp ; (155)2020 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-32009652

RESUMO

When investigating the body's mechanisms for regulating cerebral blood flow, a relative measurement of microcirculatory blood flow can be obtained using laser Doppler flowmetry (LDF). This paper demonstrates a closed skull preparation that allows cerebral blood flow to be assessed without penetrating the skull or installing a chamber or cerebral window. To evaluate autoregulatory mechanisms, a model of controlled blood pressure reduction via graded hemorrhage can be utilized while simultaneously employing LDF. This enables the real time tracking of the relative changes in the blood flow in response to reductions in arterial blood pressure produced by the withdrawal of circulating blood volume. This paradigm is a valuable approach to study cerebral blood flow autoregulation during reductions in arterial blood pressure and, with minor modifications in the protocol, is also valuable as an experimental model of hemorrhagic shock. In addition to evaluating autoregulatory responses, LDF can be used to monitor the cortical blood flow when investigating metabolic, myogenic, endothelial, humoral, or neural mechanisms that regulate cerebral blood flow and the impact of various experimental interventions and pathological conditions on cerebral blood flow.


Assuntos
Circulação Cerebrovascular/fisiologia , Homeostase , Fluxometria por Laser-Doppler/métodos , Anestesia , Animais , Artérias/fisiopatologia , Pressão Sanguínea/fisiologia , Hemorragia/fisiopatologia , Homeostase/fisiologia , Lasers , Masculino , Microcirculação/fisiologia , Ratos Sprague-Dawley
16.
Am J Cardiol ; 125(6): 924-930, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954508

RESUMO

The prevalence of coexisting coronary artery disease (CAD) is high in patients who underwent transcatheter aortic valve implantation (TAVI). Our objective was to first determine if the severity of CAD before TAVI had an important impact on post-TAVI outcomes and second, if revascularization with percutaneous coronary intervention (PCI) before TAVI modified this relation. In this retrospective population-based study in Ontario, Canada, we identified all patients with obstructive CAD who underwent TAVI from April 1, 2012 to March 31, 2017. Our primary outcomes of interest were all-cause mortality within 30-day and 1-year post-TAVI procedure. Secondary outcomes included 30-day and 1-year all-cause readmissions. We developed multivariable Cox proportional hazard models, with a robust sandwich-type variance estimator to account for clustering within TAVI centers. These models included an interaction term between severity of CAD and PCI before TAVI. The study cohort included 888 of whom 444 (50%) patients underwent PCI before TAVI procedure. In the Cox models, we found that severity of CAD before TAVI was not significantly associated with post-TAVI outcomes. The only exception was 1 to 2 vessel/s disease which was a significant predictor of 1-year readmission. Pre-TAVI PCI was not significantly associated with outcomes, nor did it modify the relation between severity of CAD pre-TAVI and outcomes. In conclusion, we did not find a consistent relation between severity of CAD and revascularization with post-TAVI outcomes.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Hemorragia/etiologia , Revascularização Miocárdica , Substituição da Valva Aórtica Transcateter , Disfunção Ventricular Esquerda/diagnóstico , Idoso , Causas de Morte , Estudos de Coortes , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Correlação de Dados , Feminino , Hemorragia/mortalidade , Hemorragia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/mortalidade , Ontário , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Substituição da Valva Aórtica Transcateter/mortalidade , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia
17.
J Trauma Acute Care Surg ; 88(2): 292-297, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31999656

RESUMO

BACKGROUND: Junctional hemorrhage is a leading contributor to battlefield mortality. The Abdominal Aortic and Junctional Tourniquet (AAJT) and infrarenal (zone III) resuscitative endovascular balloon occlusion of the aorta (REBOA) are emerging strategies for controlling junctional hemorrhage, with AAJT currently available in select forward deployed settings and increasing interest in applying REBOA in the military prehospital environment. This study compared the hemostatic, hemodynamic, and metabolic effects of these devices used for junctional hemorrhage control. METHODS: Shock was induced in anesthetized, mechanically ventilated swine with a controlled hemorrhage (20 mL/kg) and closed femur fracture followed by uncontrolled hemorrhage from a partial femoral artery transection (40% total hemorrhage volume). Residual femoral hemorrhage was recorded during 60-minute AAJT (n = 10) or zone III REBOA (n = 10) deployment, and the arterial injury was repaired subsequently. Animals were resuscitated with 15 mL/kg autologous whole blood and observed for 6 hours. RESULTS: One animal in each group died during observation. Both devices achieved hemostasis with mean residual femoral blood loss in the AAJT and REBOA groups of 0.38 ± 0.59 mL/kg and 0.10 ± 0.07 mL/kg (p = 0.16), respectively, during the 60-minute intervention. The AAJT and REBOA augmented proximal blood pressure equally with AAJT allowing higher distal pressure than REBOA during intervention (p < 0.01). Following device deflation, AAJT animals had transiently lower mean arterial blood pressure than REBOA pigs (39 ± 6 vs. 54 ± 11 mm Hg p = 0.01). Both interventions resulted in similar degrees of lactic acidemia which resolved during observation. Similar cardiac and renal effects were observed between AAJT and REBOA. CONCLUSION: The AAJT and REBOA produced similar hemostatic, resuscitative, and metabolic effects in this model of severe shock with junctional hemorrhage. Both interventions may have utility in future military medical operations.


Assuntos
Aorta Abdominal/cirurgia , Oclusão com Balão/métodos , Procedimentos Endovasculares/métodos , Hemorragia/fisiopatologia , Hemorragia/cirurgia , Hemostasia Cirúrgica/instrumentação , Animais , Feminino , Artéria Femoral/lesões , Hemodinâmica , Hemorragia/etiologia , Hemostasia Cirúrgica/efeitos adversos , Hemostasia Cirúrgica/métodos , Modelos Anatômicos , Modelos Animais , Suínos , Índices de Gravidade do Trauma , Lesões do Sistema Vascular/complicações , Lesões do Sistema Vascular/cirurgia
18.
Sci Rep ; 10(1): 1257, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988341

RESUMO

End-expiratory occlusion test (EEOT) has been proposed as a preload responsiveness test that overcomes several limitations of pulse pressure (PPV) and stroke volume (SVV) variations. We compared the ability of EEOT versus SVV and PPV to predict fluid responsiveness during the increase of the vasomotor tone in a rabbit model of hemorrhage. Ten rabbits were anesthetized, paralyzed, and mechanically ventilated during basal load (BL), after progressive blood withdrawal (BW), and after volume replacement. Other two sets of data were obtained during vasomotor increase by phenylephrine (PHE) infusion in BL and BW. We estimated the change of stroke volume (∆SVEEOT) and aortic flow (∆AoFEEOT) during the EEOT. PPV and SVV were obtained by the variation of beat-to-beat PP and SV, respectively. Baseline PPV, SVV, ∆SVEEOT, and ∆AoFEEOT increased significantly after BW, with a decrease of aortic flow (P < 0.05). PHE induced a significant decrease of PPV and SVV, but without affecting ∆SVEEOT, and ∆AoFEEOT. We conclude that ∆SV and ∆AoF during EEOT kept the ability to predict fluid responsiveness during PHE infusion in a rabbit hemorrhage model. This result may suggest the advantage of EEOT with respect to SVV and PPV in predicting fluid responsiveness during vasomotor tone increase.


Assuntos
Hemorragia/fisiopatologia , Respiração com Pressão Positiva/métodos , Animais , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Feminino , Hidratação/métodos , Hemodinâmica , Monitorização Fisiológica/métodos , Fenilefrina/farmacologia , Coelhos , Volume Sistólico/fisiologia , Sistema Vasomotor
19.
PLoS One ; 14(12): e0226146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31821374

RESUMO

Mild systemic hypothermia increases gastric mucosal oxygenation (µHbO2) during hemorrhagic shock in dogs. In the context of critical blood loss hypothermia might be fatal due to adverse side effects. Selective regional hypothermia might overcome these limitations. The aim of our study was to analyze the effects of regional gastric and oral mucosal hypothermia on µHbO2 and perfusion (µflow). In a cross-over study six anesthetized dogs were subjected to local oral and gastric mucosal hypothermia (34°C), or maintenance of local normothermia during normovolemia and hemorrhage (-20% blood volume). Macro- and microcirculatory variables were recorded continuously. During normovolemia, local hypothermia increased gastric microcirculatory flow (µflow) without affecting oxygenation (µHbO2) or oral microcirculation. During mild hemorrhagic shock gastric µHbO2 decreased from 72±2% to 38±3% in the normothermic group. This was attenuated by local hypothermia, where µHbO2 was reduced from 74±3% to 52±4%. Local perfusion, oral microcirculation and macrocirculatory variables were not affected. Selective local hypothermia improves gastric µHbO2 during hemorrhagic shock without relevant side effects. In contrast to systemic hypothermia, regional mucosal hypothermia did not affect perfusion and oxygen supply during hemorrhage. Thus, the increased µHbO2 during local hypothermia rather indicates reduced mucosal oxygen demand.


Assuntos
Hemorragia/terapia , Hipotermia Induzida , Microcirculação , Estômago/irrigação sanguínea , Animais , Estudos Cross-Over , Cães , Feminino , Hemorragia/fisiopatologia , Oxigênio/sangue
20.
PLoS One ; 14(10): e0223406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31581265

RESUMO

Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. This study sought to explore the molecular mechanisms of TXA activity in trauma and determine whether administration of TXA as a supplement to FWB resuscitation could attenuate the established ATC in a rat model simulating prehospital resuscitation of polytrauma and hemorrhagic shock. In a parallel in-vitro study, the effects on clotting assays of adding plasmin at varying doses along with either simultaneous addition of TXA or pre-incubation with TXA were measured, and the results suggested that maximum anti-fibrinolytic effect of TXA on plasmin-induced fibrinolysis required pre-incubation of TXA and plasmin prior to clot initiation. In the rat model, ATC was induced by polytrauma followed by 40% hemorrhage. One hour after trauma, the rats were resuscitated with FWB collected from donor rats. Vehicle or TXA (10mg/kg) was given as bolus either before trauma (TXA-BT), or 45min after trauma prior to resuscitation (TXA-AT). The TXA-BT group was included to contrast the coagulation effects of TXA when used as it is in elective surgery vs. what is actually feasible in real trauma patients (TXA-AT group). A single dose of TXA prior to trauma significantly delayed the onset of ATC from 30min to 120min after trauma as measured by a rise in prothrombin time (PT). The plasma d-dimer as well as plasminogen/fibrinogen ratio in traumatized liver of TXA-BT were significantly lower as compared to vehicle and TXA-AT. Wet/dry weight ratio and leukocytes infiltration of lungs were significantly decreased only if TXA was administrated later, prior to resuscitation (TXA-AT). In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA's various sites and modes of action may further improve patient outcomes.


Assuntos
Antifibrinolíticos/administração & dosagem , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/sangue , Hemorragia/etiologia , Traumatismo Múltiplo/complicações , Ácido Tranexâmico/administração & dosagem , Animais , Biomarcadores , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/fisiopatologia , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Hemorragia/tratamento farmacológico , Hemorragia/fisiopatologia , Humanos , Imuno-Histoquímica , Masculino , Traumatismo Múltiplo/etiologia , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA