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1.
Eur Rev Med Pharmacol Sci ; 25(19): 5922-5927, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34661250

RESUMO

Systemic capillary leak syndrome (SCLS) is a very rare and lethal disease characterized by hemoconcentration and hypoalbuminemia caused by reversible plasma extravasation. The underlying cause for SCLS remains largely unknown and acute treatment has remained mainly supportive. Prophylaxis with intravenous immunoglobulin (IVIG) has been shown to successfully prevent further episodes in affected patients. We reported a case of SCLS in a patient who presented to our hospital with COVID-19 and developed profound shock.


Assuntos
COVID-19/patologia , Síndrome de Vazamento Capilar/patologia , COVID-19/complicações , COVID-19/diagnóstico por imagem , Síndrome de Vazamento Capilar/complicações , Síndrome de Vazamento Capilar/diagnóstico por imagem , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/patologia , Choque/etiologia , Choque/patologia , Tomografia Computadorizada por Raios X
2.
PLoS One ; 16(10): e0258811, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34695147

RESUMO

Hemorrhage, a main cause of mortality in patients with trauma, affects vital signs such as blood pressure and heart rate. Shock index (SI), calculated as heart rate divided by systolic blood pressure, is widely used to estimate the shock status of patients with hemorrhage. The difference in SI between the emergency department and prehospital field can indirectly reflect urgency after trauma. We aimed to determine the association between delta SI (DSI) and in-hospital mortality in patients with torso or extremity trauma. Patients with DSI >0.1 are expected to be associated with high mortality. This retrospective, observational study used data from the Pan-Asian Trauma Outcomes Study. Patients aged 18-85 years with abdomen, chest, upper extremity, lower extremity, or external injury location were included. Patients from China, Indonesia, Japan, Philippines, Thailand, and Vietnam; those who were transferred from another facility; those who were transferred without the use of emergency medical service; those with prehospital cardiac arrest; those with unknown exposure and outcomes were excluded. The exposure and primary outcome were DSI and in-hospital mortality, respectively. The secondary and tertiary outcome was intensive care unit (ICU) admission and massive transfusion, respectively. Multivariate logistic regression analysis was performed to test the association between DSI and outcome. In total, 21,534 patients were enrolled according to the inclusion and exclusion criteria. There were 3,033 patients with DSI >0.1. The in-hospital mortality rate in the DSI >0.1 and ≤0.1 groups was 2.0% and 0.8%, respectively. In multivariate logistic regression analysis, the DSI ≤0.1 group was considered the reference group. The unadjusted and adjusted odds ratios of in-hospital mortality in the DSI >0.1 group were 2.54 (95% confidence interval [CI] 1.88-3.42) and 2.82 (95% CI 2.08-3.84), respectively. The urgency of traumatic hemorrhage can be determined using DSI, which can help hospital staff to provide proper trauma management, such as early trauma surgery or embolization.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Extremidades/patologia , Mortalidade Hospitalar/tendências , Doenças Musculoesqueléticas/complicações , Choque/mortalidade , Tronco/patologia , Ferimentos e Lesões/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Sistema de Registros , Estudos Retrospectivos , Choque/etiologia , Choque/patologia , Taxa de Sobrevida , Adulto Jovem
3.
Pediatr Cardiol ; 42(8): 1871-1878, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34448042

RESUMO

Elevated magnetic resonance elastography (MRE)-derived liver stiffness may be associated with worse outcomes in people with Fontan circulation. We sought to evaluate the association between liver stiffness and Fontan failure or portal hypertension. Single center cross-sectional retrospective study of people with Fontan circulation who underwent MRE between 2011 and 2020. The cohort was divided into adult (age ≥ 21 years) and pediatric (< 21 years) groups. Fontan circulatory failure (FF) was defined as any of the following: death, transplantation, ventricular assist device, heart failure symptoms requiring escalation of diuretics. Radiologic portal hypertension was defined as the presence of one or more of the following: splenomegaly, ascites, or gastrointestinal varices. 128 patients were included (average age = 22.6 ± 8.7 years) and 58 (45%) were children. Median liver stiffness was 4.3 kPa (interquartile range (IQR) 3.8-5.8) for the entire cohort. Thirty patients (23%) developed FF (16 adults, 14 children). Liver stiffness was higher in adults with FF compared to those without FF (4.9 (IQR 4.0-6.0) vs. 4.2 (IQR 3.8-4.7) kPa, p = 0.04). There was no difference in liver stiffness between pediatric patients with and without FF (4.4 (IQR 4.1-5.4) vs. 4.4 (IQR 3.8-5.0), p = 0.5). Adults with radiologic portal hypertension and adults with moderate or severe atrioventricular valve regurgitation had higher liver stiffness than adults without. MRE-derived liver stiffness is associated with atrioventricular valve regurgitation, portal hypertension, and poor clinical outcomes in adults with Fontan circulation. There was no association between liver stiffness and FF in pediatric patients. This difference may be due to the progressive nature of Fontan-associated liver disease.


Assuntos
Técnicas de Imagem por Elasticidade , Técnica de Fontan , Choque , Adolescente , Adulto , Criança , Estudos Transversais , Técnica de Fontan/efeitos adversos , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/patologia , Estudos Retrospectivos , Choque/patologia , Adulto Jovem
5.
Crit Care Med ; 49(11): e1151-e1156, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34049308

RESUMO

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.


Assuntos
COVID-19/complicações , Choque/patologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , Corticosteroides/uso terapêutico , Angiopoietina-2/sangue , Biomarcadores , Proteína C-Reativa/análise , COVID-19/tratamento farmacológico , COVID-19/patologia , Cardiotônicos/uso terapêutico , Criança , Feminino , Humanos , Imunoglobulinas/uso terapêutico , Unidades de Terapia Intensiva Pediátrica , Interleucina-6/sangue , Ácido Láctico/sangue , Masculino , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Choque Cardiogênico/patologia , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Troponina/sangue , Vasoconstritores/uso terapêutico , Função Ventricular Esquerda
6.
PLoS One ; 16(5): e0251908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34015006

RESUMO

The Non-Pneumatic Anti-Shock Garment (NASG) is a first aid tool that can halt and reverse hypovolemic shock secondary to obstetric hemorrhage. The World Health Organization recommended the NASG for use as a temporizing measure in 2012, but uptake of the recommendation has been slow, partially because operational experience is limited. The study is a process evaluation of the introduction of NASG in a public sector health facility network in rural Zimbabwe utilizing an adapted RE-AIM, categorizing observations into the domains of: reach, effectiveness, adoption, implementation and maintenance. The location of the study was Hurungwe district, where staff members of 34 health facilities at primary (31), secondary (2) and tertiary (1) levels of care participated. We found that all facilities became skilled in using the NASG, and that the NASG was used in 10 of 11 instances of severe hemorrhage. In the cases of hypovolemic shock where the NASG was used, there were no maternal deaths and no extreme adverse outcomes related to obstetric hemorrhage in the study period. Among the 10 NASG uses, the garment was used correctly in each case. Fidelity to processes was high, especially in regard to training and cascading skills, but revisions of the NASG rotation and replacement operating procedures were required to keep clean garments stocked. Clinical documentation was also a key challenge. NASG introduction dovetailed very well with pre-existing systems for obstetric emergency response, and improved clinical outcomes. Scale-up of the NASG in the Zimbabwean public health system can be undertaken with careful attention to mentorship, drills, documentation and logistics.


Assuntos
Complicações do Trabalho de Parto/terapia , Hemorragia Pós-Parto/terapia , Complicações Hematológicas na Gravidez/terapia , Choque/terapia , Adulto , Vestuário , Feminino , Primeiros Socorros , Humanos , Morte Materna , Complicações do Trabalho de Parto/epidemiologia , Complicações do Trabalho de Parto/patologia , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/patologia , Choque/epidemiologia , Choque/patologia , Organização Mundial da Saúde , Zimbábue/epidemiologia
7.
J Korean Med Sci ; 36(2): e7, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33429471

RESUMO

BACKGROUND: A rapid response system (RRS) contributes to the safety of hospitalized patients. Clinical deterioration may occur in the general ward (GW) or in non-GW locations such as radiology or dialysis units. However, there are few studies regarding RRS activation in non-GW locations. This study aimed to compare the clinical characteristics and outcomes of patients with RRS activation in non-GW locations and in the GW. METHODS: From January 2016 to December 2017, all patients requiring RRS activation in nine South Korean hospitals were retrospectively enrolled and classified according to RRS activation location: GW vs non-GW RRS activations. RESULTS: In total, 12,793 patients were enrolled; 222 (1.7%) were non-GW RRS activations. There were more instances of shock (11.6% vs. 18.5%) and cardiac arrest (2.7% vs. 22.5%) in non-GW RRS activation patients. These patients also had a lower oxygen saturation (92.6% ± 8.6% vs. 88.7% ± 14.3%, P < 0.001) and a higher National Early Warning Score 2 (7.5 ± 3.4 vs. 8.9 ± 3.8, P < 0.001) than GW RRS activation patients. Although non-GW RRS activation patients received more intubation (odds ratio [OR], 3.135; P < 0.001), advanced cardiovascular life support (OR, 3.912; P < 0.001), and intensive care unit transfer (OR, 2.502; P < 0.001), their hospital mortality (hazard ratio, 0.630; P = 0.013) was lower than GW RRS activation patients upon multivariate analysis. CONCLUSION: Considering that there were more critically ill but recoverable cases in non-GW locations, active RRS involvement should be required in such locations.


Assuntos
Equipe de Respostas Rápidas de Hospitais , Estudos de Coortes , Parada Cardíaca/patologia , Mortalidade Hospitalar , Equipe de Respostas Rápidas de Hospitais/organização & administração , Humanos , Unidades de Terapia Intensiva , Razão de Chances , Transferência de Pacientes , Quartos de Pacientes , República da Coreia , Estudos Retrospectivos , Choque/patologia
13.
Shock ; 54(1): 1-3, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32530843
14.
Sci Rep ; 10(1): 8462, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439972

RESUMO

Bile acids (BA), with their large hydrophobic steroid nucleus and polar groups are amphipathic molecules. In bile, these exist as micelles above their critical micellar concentration (CMC). In blood at low concentrations, these exist as monomers, initiating cellular signals. This micellar to monomer transition may involve complex thermodynamic interactions between bile salts alone or with phospholipids, i.e. mixed micelles and the aqueous environment. We therefore went on to test if therapeutically relevant changes in temperature could influence micellar behavior of bile salts, and in turn whether this affected the biological responses in cells, and in vivo. Sodium taurocholate (STC) belongs to a major class of bile salts. STC has a CMC in the 5-8 mM range and its infusion into the pancreatic duct is commonly used to study pancreatitis. We thus studied micellar breakdown of STC using isothermal titration calorimetry (ITC), dynamic light scattering and cryogenic transmission electron microscopy. Under conditions relevant to the in vivo environment (pH 7.4, Na 0.15 M), ITC showed STC to have a U shaped reduction in micellar breakdown between 37 °C and 15 °C with a nadir at 25 °C approaching ≈90% inhibition. This temperature dependence paralleled pancreatic acinar injury induced by monomeric STC. Mixed micelles of STC and 1-palmitoyl, 2-oleyl phosphatidylcholine, a phospholipid present in high proportions in bile, behaved similarly, with ≈75% reduction in micellar breakdown at 25 °C compared to 37 °C. In vivo pancreatic cooling to 25 °C reduced the increase in circulating BAs after infusion of 120 mM (5%) STC into the pancreatic duct, and duct ligation. Lower BA levels were associated with improved cardiac function, reduced myocardial damage, shock, lung injury and improved survival independent of pancreatic injury. Thus micellar breakdown of bile salts is essential for their entry into the systemic circulation, and thermodynamic interference with this may reduce their systemic entry and consequent injury during cholestasis, such as from biliary pancreatitis.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colestase/complicações , Inflamação/prevenção & controle , Lesão Pulmonar/prevenção & controle , Micelas , Contusões Miocárdicas/prevenção & controle , Choque/prevenção & controle , Animais , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos , Contusões Miocárdicas/etiologia , Contusões Miocárdicas/metabolismo , Contusões Miocárdicas/patologia , Choque/etiologia , Choque/metabolismo , Choque/patologia , Temperatura , Termodinâmica
15.
Sci Rep ; 10(1): 2095, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034233

RESUMO

The reverse shock index (rSI), a ratio of systolic blood pressure (SBP) to heart rate (HR), is used to identify prognosis in trauma patients. Multiplying rSI by Glasgow Coma Scale (rSIG) can possibly predict better in-hospital mortality in patients with trauma. However, rSIG has never been used to evaluate the mortality risk in adult severe trauma patients (Injury Severity Score [ISS] ≥ 16) with head injury (head Abbreviated Injury Scale [AIS] ≥ 2) in the emergency department (ED). This retrospective case control study recruited adult severe trauma patients (ISS ≥ 16) with head injury (head AIS ≥ 2) who presented to the ED of two major trauma centers between January 01, 2014 and May 31, 2017. Demographic data, vital signs, ISS scores, injury mechanisms, laboratory data, managements, and outcomes were included for the analysis. Logistic regression and receiver operating characteristic analysis were used to evaluate the accuracy of rSIG score in predicting in-hospital mortality. In total, 438 patients (mean age: 56.48 years; 68.5% were males) were included in this study. In-hospital mortality occurred in 24.7% patients. The median (interquartile range) ISS score was 20 (17-26). Patients with rSIG ≤ 14 had seven-fold increased risks of mortality than those without rSIG ≤ 14 (odds ratio: 7.64; 95% confidence interval: 4.69-12.42). Hosmer-Lemeshow goodness-of-fit test and area under the curve values for rSIG score were 0.29 and 0.76, respectively. The sensitivity, specificity, positive predictive value, and negative predictive values of rSIG ≤ 14 were 0.71, 0.75, 0.49, and 0.89, respectively. The rSIG score is a prompt and simple tool to predict in-hospital mortality among adult severe trauma patients with head injury.


Assuntos
Traumatismos Craniocerebrais/mortalidade , Escala de Coma de Glasgow , Índice de Gravidade de Doença , Ferimentos e Lesões/mortalidade , Escala Resumida de Ferimentos , Pressão Sanguínea , Estudos de Casos e Controles , Traumatismos Craniocerebrais/diagnóstico , Feminino , Escala de Coma de Glasgow/estatística & dados numéricos , Frequência Cardíaca , Humanos , Escala de Gravidade do Ferimento , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Choque/diagnóstico , Choque/patologia , Análise de Sobrevida , Ferimentos e Lesões/diagnóstico
17.
Shock ; 53(5): 646-652, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31454826

RESUMO

Resuscitation with human fresh frozen plasma (FFP) in hemorrhagic shock (HS) patients is associated with improved clinical outcomes. Our group has demonstrated that the beneficial effect of FFP is due to its blockade on endothelial hyperpermeability, thereby improving vascular barrier function. The current study aimed to investigate HS-induced endothelial cell apoptosis, a potential major contributor to the endothelial hyperpermeability, and to determine the effect and the key components/factors of FFP on protecting endothelial cells from apoptosis. We first measured and demonstrated an increase in apoptotic endothelial microparticles (CD146AnnexinV) in patients in shock compared to normal subjects, indicating the induction of endothelial cell activation and apoptosis in shock patients. We then transfused HS rats with FFP and showed that FFP blocked HS-induced endothelial cell apoptosis in gut tissue. To identify the anti-apoptotic factors in FFP, we utilized high-performance liquid chromatography, fractionated FFP, and screened the fractions in vitro for the anti-apoptotic effects. We selected the most effective fractions, performed mass spectrometry, and identified fibrinogen as a potent anti-apoptotic factor. Taken together, our findings suggest that HS-induced endothelial apoptosis may constitute a major mechanism underlying the vascular hyperpermeability. Furthermore, the identified anti-apoptotic factor fibrinogen may contribute to the beneficial effects of FFP resuscitation, and therefore, may have therapeutic potential for HS.


Assuntos
Células Endoteliais/fisiologia , Fibrinogênio/fisiologia , Plasma/citologia , Choque/patologia , Choque/terapia , Ferimentos e Lesões/complicações , Animais , Apoptose , Estudos de Casos e Controles , Técnicas de Cultura de Células , Citoproteção , Modelos Animais de Doenças , Células Endoteliais/patologia , Humanos , Ratos , Ferimentos e Lesões/patologia , Ferimentos e Lesões/terapia
18.
Aliment Pharmacol Ther ; 51(2): 253-260, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642558

RESUMO

BACKGROUND: Acute upper gastrointestinal bleeding (UGIB) remains a major cause of hospital admission worldwide. The recent UK National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report on severe gastrointestinal bleeding used the Shock Index to assess bleeding severity and found an association between Shock Index and mortality. However, this has never been prospectively validated as a predictor of outcome in UGIB. AIMS: To compare the Shock Index with existing pre-endoscopic UGIB risk scores in predicting outcomes after UGIB METHODS: In an international, prospective study of 3012 consecutive patients with UGIB, we compared the Shock Index with existing scores including the Glasgow Blatchford score (GBS), admission Rockall score, AIMS65, and the newly described "ABC" score. Pre-determined endpoints were need for major (≥4 units red cells) transfusion, need for endoscopic therapy and 30-day mortality. RESULTS: The Shock Index was inferior to the GBS in predicting need for major transfusion (area under the receiver operator characteristic curve [AUROC] 0.655 vs 0.836, P < 0.001) and need for endotherapy (AUROC 0.606 vs 0.747, P < 0.001). The Shock Index was inferior to all other scores for 30-day mortality: for example, AUROC 0.611 vs 0.863 for ABC score (P < 0.001). Adding the Shock Index to the ABC score did not improve accuracy of the ABC score in predicting mortality (AUROC 0.864 vs 0.863, P = 0.95). CONCLUSION: The Shock Index performed poorly with AUROCs <0.66 and was inferior to existing pre-endoscopy scores at predicting major clinical endpoints after UGIB. We found no clear evidence that the Shock Index is clinically useful at predicting outcomes in UGIB. [Correction added on 20 December 2019, after first online publication: Summary section has been changed for clarification.].


Assuntos
Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/mortalidade , Índice de Gravidade de Doença , Choque/diagnóstico , Trato Gastrointestinal Superior/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Transfusão de Sangue/mortalidade , Transfusão de Sangue/estatística & dados numéricos , Estudos de Coortes , Endoscopia Gastrointestinal , Feminino , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/patologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Choque/etiologia , Choque/mortalidade , Choque/patologia , Análise de Sobrevida , Trato Gastrointestinal Superior/patologia , Adulto Jovem
19.
J Trauma Acute Care Surg ; 87(5): 1070-1076, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31658237

RESUMO

BACKGROUND: Ischemia/reperfusion injury (IRI) has been shown to cause endothelial glycocalyx (EG) damage.Whether the hypoxic/ischemic insult or the oxidative and inflammatory stress of reperfusion plays a greater part in glycocalyx damage is not known. Furthermore, the mechanisms by which IRI causes EG damage have not been fully elucidated. The aims of this study were to determine if hypoxia alone or hypoxia/reoxygenation (H/R) caused greater damage to the glycocalyx, and if this damage was mediated by reactive oxygen species (ROS) and Ca signaling. METHODS: Human umbilical vein endothelial cells were cultured to confluence and exposed to either normoxia (30 minutes), hypoxia (2% O2 for 30 minutes), or H/R (30 minutes hypoxia followed by 30 minutes normoxia). Some cells were pretreated with ROS scavengers TEMPOL, MitoTEMPOL, Febuxostat, or Apocynin, or with the Ca chelator BAPTA or Ca channel blockers 2-aminoethoxydiphenyl borate, A967079, Pyr3, or ML204. Intracellular ROS was quantified for all groups. Endothelial glycocalyx was measured using fluorescently tagged wheat germ agglutinin and imaged with fluorescence microscopy. RESULTS: Glycocalyx thickness was decreased in both hypoxia and H/R groups, with the decrease being greater in the H/R group. TEMPOL, MitoTEMPOL, BAPTA, and 2-aminoethoxydiphenyl borate prevented loss of glycocalyx in H/R. The ROS levels were likewise elevated compared with normoxia in both groups, but were increased in the H/R group compared with hypoxia alone. BAPTA did not prevent ROS production in either group. CONCLUSION: In our cellular model for shock, we demonstrate that although hypoxia alone is sufficient to produce glycocalyx loss, H/R causes a greater decrease in glycocalyx thickness. Under both conditions damage is dependent on ROS and Ca signaling. Notably, we found that ROS are generated upstream of Ca, but that ROS-mediated damage to the glycocalyx is dependent on Ca.


Assuntos
Sinalização do Cálcio/fisiologia , Endotélio/patologia , Glicocálix/patologia , Traumatismo por Reperfusão/fisiopatologia , Choque/fisiopatologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Hipóxia Celular/fisiologia , Linhagem Celular , Quelantes/farmacologia , Endotélio/citologia , Sequestradores de Radicais Livres/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/patologia , Choque/patologia
20.
Prostaglandins Other Lipid Mediat ; 145: 106377, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31586592

RESUMO

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock, the most common form of vasodilatory shock, is a subset of sepsis in which circulatory and cellular/metabolic abnormalities are severe enough to increase mortality. Inflammatory shock constitutes the hallmark of sepsis, but also a final common pathway of any form of severe long-term tissue hypoperfusion. The pathogenesis of inflammatory shock seems to be due to circulating substances released by pathogens (e.g., bacterial endotoxins) and host immuno-inflammatory responses (e.g., changes in the production of histamine, bradykinin, serotonin, nitric oxide [NO], reactive nitrogen and oxygen species, and arachidonic acid [AA]-derived eicosanoids mainly through NO synthase, cyclooxygenase, and cytochrome P450 [CYP] pathways, and proinflammatory cytokine formation). Therefore, refractory hypotension to vasoconstrictors with end-organ hypoperfusion is a life threatening feature of inflammatory shock. This review summarizes the current knowledge regarding the role of eicosanoids derived from CYP pathway of AA in animal models of inflammatory shock syndromes with an emphasis on septic shock in addition to potential therapeutic strategies targeting specific CYP isoforms responsible for proinflammatory/anti-inflammatory mediator production.


Assuntos
Ácido Araquidônico/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Óxido Nítrico Sintase/metabolismo , Choque/metabolismo , Animais , Humanos , Inflamação/metabolismo , Inflamação/patologia , Choque/patologia
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