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1.
Br J Anaesth ; 131(4): 739-744, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37604735

RESUMO

BACKGROUND: Arterial catheterisation in children can be challenging and time-consuming. We aimed to compare the success rates of ultrasound-guided arterial catheterisation utilising the short-axis out-of-plane approach with dynamic needle tip positioning in the radial, dorsalis pedis, and posterior tibial arteries in paediatric patients. We also examined the factors influencing the catheterisation success using dynamic needle tip positioning. METHODS: Paediatric patients (aged <3 yr) undergoing cardiac surgery were randomly assigned to three groups based on puncture sites: radial artery (Group R), dorsalis pedis artery (Group D), and posterior tibial artery (Group P). The first-attempt and overall success rates of arterial catheterisation were compared, followed by multiple logistic regression analysis (dependent variable: first-attempt success; independent variables: body weight, diameter and depth of the artery, targeted artery, and trisomy 21). RESULTS: The study included 270 subjects (n=90 per group). There was no significant difference in the first-attempt (Group R: 82%, Group D: 76%, and Group P: 81%) and overall success rates (Group R: 94%, Group D: 93%, and Group P: 91%) among the three groups. The diameter of the artery (per 0.1 mm) (odds ratio: 1.32, 95% confidence interval: 1.09-1.60) and trisomy 21 (odds ratio: 0.43, 95% confidence interval: 0.20-0.92) were independent predictors of first-attempt success or failure. CONCLUSION: The first-attempt and overall success rates of arterial catheterisation of the dorsalis pedis and posterior tibial arteries were not inferior to those in the radial artery when using dynamic needle tip positioning. These two lower extremity peripheral arteries present viable alternative catheterisation sites in paediatric patients. CLINICAL TRIAL REGISTRATION: UMIN000042847.


Assuntos
Síndrome de Down , Artérias da Tíbia , Humanos , Criança , Artérias da Tíbia/diagnóstico por imagem , Artéria Radial/diagnóstico por imagem , Extremidade Inferior , Ultrassonografia de Intervenção
2.
J Cardiothorac Vasc Anesth ; 37(10): 2057-2064, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37217420

RESUMO

OBJECTIVES: To compare the efficacy of the ultrasound-guided approach with and without dynamic needle-tip positioning and the palpation technique regarding success for peripheral venous catheterization in children. DESIGN: A systematic review with network meta-analysis. SETTING: Databases of MEDLINE (via PubMed) and Cochrane Central Register of Controlled Trials. PARTICIPANTS: Patients (<18 years) undergoing peripheral venous catheter insertion. INTERVENTIONS: Randomized clinical trials were included to compare the following techniques: the ultrasound-guided short-axis out-of-plane approach with dynamic needle-tip positioning, the approach without dynamic needle-tip positioning, and the palpation technique. MEASUREMENTS AND MAIN RESULTS: The outcomes were first-attempt and overall success rates. Eight studies were included in the qualitative analyses. According to the estimate of network comparison, dynamic needle-tip positioning was associated with higher first-attempt (risk ratio [RR] 1.67; 95% CI 1.33-2.09) and overall success rates (RR 1.25; 95% CI 1.08-1.44) than palpation. The approach without dynamic needle-tip positioning was not associated with higher first-attempt (RR 1.17; 95% CI 0.91-1.49) and overall success rates (RR 1.10; 95% CI 0.90-1.33) than palpation. Compared to the approach without dynamic needle-tip positioning, dynamic needle-tip positioning was associated with a higher first-attempt success rate (RR 1.43; 95% CI 1.07-1.92), but not a higher overall success rate (RR 1.14; 95% CI 0.92-1.41). CONCLUSIONS: Dynamic needle-tip positioning is efficacious for peripheral venous catheterization in children. It would be better to include dynamic needle-tip positioning for the ultrasound-guided short-axis out-of-plane approach.


Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Humanos , Criança , Metanálise em Rede , Ultrassonografia de Intervenção/métodos , Cateterismo Periférico/métodos , Ultrassonografia , Agulhas , Cateterismo Venoso Central/métodos
3.
Anaesth Crit Care Pain Med ; 42(3): 101206, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36858256

RESUMO

The efficacy of the short-axis out-of-plane (SA-OOP) approach with and without dynamic needle tip positioning (DNTP) remains unclear. This systematic review with network meta-analysis aimed to compare the success rate of arterial line insertion in children using the SA-OOP approach with and without DNTP and the palpation technique. We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials. We included randomized controlled trials that compared two of the following techniques for arterial line insertion in children: (1) the ultrasound-guided SA-OOP approach with DNTP; (2) the ultrasound-guided SA-OOP approach without DNTP; and (3) the palpation technique. A network meta-analysis was performed. The outcomes were first-attempt and overall success rates. Eight studies were finally included in this network meta-analysis. The ultrasound-guided SA-OOP approach with DNTP was associated with increased first-attempt (relative risk RR = 3.45 [95% confidence interval (CI) 2.51-4.74]) and overall success rates (RR = 1.81 [1.41-2.32]) when compared with palpation. The same approach performed without DNTP was also associated with increased first-attempt (RR = 1.96 [1.59-2.42]) and overall success rates (RR = 1.25 [1.05-1.49]) when compared with palpation. The ultrasound-guided SA-OOP approach with DNTP was associated with increased first-attempt (RR = 1.76 [1.26-2.44]) and overall success rates (RR = 1.45 [1.10-1.91]) when compared with the same approach performed without DNTP. DNTP should be performed during the ultrasound-guided SA-OOP approach for arterial line insertion in children, as this can help increase first attempt and overall success rates.


Assuntos
Cateterismo Periférico , Dispositivos de Acesso Vascular , Humanos , Criança , Ultrassonografia de Intervenção/métodos , Cateterismo Periférico/métodos , Metanálise em Rede , Artéria Radial/diagnóstico por imagem
4.
Circ Res ; 131(6): 510-527, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-35950500

RESUMO

BACKGROUND: An ancient family of arrestin-fold proteins, termed alpha-arrestins, may have conserved roles in regulating nutrient transporter trafficking and cellular metabolism as adaptor proteins. One alpha-arrestin, TXNIP (thioredoxin-interacting protein), is known to regulate myocardial glucose uptake. However, the in vivo role of the related alpha-arrestin, ARRDC4 (arrestin domain-containing protein 4), is unknown. METHODS: We first tested whether interaction with GLUTs (glucose transporters) is a conserved function of the mammalian alpha-arrestins. To define the in vivo function of ARRDC4, we generated and characterized a novel Arrdc4 knockout (KO) mouse model. We then analyzed the molecular interaction between arrestin domains and the basal GLUT1. RESULTS: ARRDC4 binds to GLUT1, induces its endocytosis, and blocks cellular glucose uptake in cardiomyocytes. Despite the closely shared protein structure, ARRDC4 and its homologue TXNIP operate by distinct molecular pathways. Unlike TXNIP, ARRDC4 does not increase oxidative stress. Instead, ARRDC4 uniquely mediates cardiomyocyte death through its effects on glucose deprivation and endoplasmic reticulum stress. At baseline, Arrdc4-KO mice have mild fasting hypoglycemia. Arrdc4-KO hearts exhibit a robust increase in myocardial glucose uptake and glycogen storage. Accordingly, deletion of Arrdc4 improves energy homeostasis during ischemia and protects cardiomyocytes against myocardial infarction. Furthermore, structure-function analyses of the interaction of ARRDC4 with GLUT1 using both scanning mutagenesis and deep-learning Artificial Intelligence identify specific residues in the C-terminal arrestin-fold domain as the interaction interface that regulates GLUT1 function, revealing a new molecular target for potential therapeutic intervention against myocardial ischemia. CONCLUSIONS: These results uncover a new mechanism of ischemic injury in which ARRDC4 drives glucose deprivation-induced endoplasmic reticulum stress leading to cardiomyocyte death. Our findings establish ARRDC4 as a new scaffold protein for GLUT1 that regulates cardiac metabolism in response to ischemia and provide insight into the therapeutic strategy for ischemic heart disease.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Infarto do Miocárdio , Isquemia Miocárdica , Animais , Arrestina/metabolismo , Arrestinas/metabolismo , Inteligência Artificial , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Mamíferos , Camundongos , Camundongos Knockout , Isquemia Miocárdica/genética , Estresse Fisiológico
5.
Am J Physiol Heart Circ Physiol ; 321(2): H259-H274, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34085839

RESUMO

Underlying molecular mechanisms for the development of diabetic cardiomyopathy remain to be determined. Long-term exposure to hyperglycemia causes oxidative stress, which leads to cardiomyocyte dysfunction. Previous studies established the importance of thioredoxin-interacting protein (Txnip) in cellular redox homeostasis and glucose metabolism. Txnip is a highly glucose-responsive molecule that interacts with the catalytic center of reduced thioredoxin and inhibits the antioxidant function of thioredoxin. Here, we show that the molecular interaction between Txnip and thioredoxin plays a pivotal role in the regulation of redox balance in the diabetic myocardium. High glucose increased Txnip expression, decreased thioredoxin activities, and caused oxidative stress in cells. The Txnip-thioredoxin complex was detected in cells with overexpressing wild-type Txnip but not Txnip cysteine 247 to serine (C247S) mutant that disrupts the intermolecular disulfide bridge. Then, diabetes was induced in cardiomyocyte-specific Txnip C247S knock-in mice and their littermate control animals by injections of streptozotocin (STZ). Prolonged hyperglycemia upregulated myocardial Txnip expression in both genotypes. The absence of Txnip's inhibition of thioredoxin in Txnip C247S mutant hearts promoted mitochondrial antioxidative capacities in cardiomyocytes, thereby protecting the heart from oxidative damage by diabetes. Stress hemodynamic analysis uncovered that Txnip C247S knock-in hearts have a greater left ventricular contractile reserve than wild-type hearts under STZ-induced diabetic conditions. These results provide novel evidence that Txnip serves as a regulator of hyperglycemia-induced cardiomyocyte toxicities through direct inhibition of thioredoxin and identify the single cysteine residue in Txnip as a therapeutic target for diabetic injuries.NEW & NORTEWORTHY Thioredoxin-interacting protein (Txnip) has been of great interest as a molecular mechanism to mediate diabetic organ damage. Here, we provide novel evidence that a single mutation of Txnip confers a defense mechanism against myocardial oxidative stress in streptozotocin-induced diabetic mice. The results demonstrate the importance of Txnip as a cysteine-containing redox protein that regulates antioxidant thioredoxin via disulfide bond-switching mechanism and identify the cysteine in Txnip as a therapeutic target for diabetic cardiomyopathy.


Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/genética , Tiorredoxinas/metabolismo , Função Ventricular Esquerda/genética , Animais , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Técnicas de Introdução de Genes , Glucose/farmacologia , Células HEK293 , Humanos , Preparação de Coração Isolado , Camundongos , Mutação , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Tiorredoxinas/genética
6.
J Mol Cell Cardiol ; 155: 36-49, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33652022

RESUMO

RATIONALE: Thioredoxin-interacting protein (Txnip) is a novel molecular target with translational potential in diverse human diseases. Txnip has several established cellular actions including binding to thioredoxin, a scavenger of reactive oxygen species (ROS). It has been long recognized from in vitro evidence that Txnip forms a disulfide bridge through cysteine 247 (C247) with reduced thioredoxin to inhibit the anti-oxidative properties of thioredoxin. However, the physiological significance of the Txnip-thioredoxin interaction remains largely undefined in vivo. OBJECTIVE: A single mutation of Txnip, C247S, abolishes the binding of Txnip with thioredoxin. Using a conditional and inducible approach with a mouse model of a mutant Txnip that does not bind thioredoxin, we tested whether the interaction of thioredoxin with Txnip is required for Txnip's pro-oxidative or cytotoxic effects in the heart. METHODS AND RESULTS: Overexpression of Txnip C247S in cells resulted in a reduction in ROS, due to an inability to inhibit thioredoxin. Hypoxia (1% O2, 24 h)-induced killing effects of Txnip were decreased by lower levels of cellular ROS in Txnip C247S-expressing cells compared with wild-type Txnip-expressing cells. Then, myocardial ischemic injuries were assessed in the animal model. Cardiomyocyte-specific Txnip C247S knock-in mice had better survival with smaller infarct size following myocardial infarction (MI) compared to control animals. The absence of Txnip's inhibition of thioredoxin promoted mitochondrial anti-oxidative capacities in cardiomyocytes, thereby protecting the heart from oxidative damage induced by MI. Furthermore, an unbiased RNA sequencing screen identified that hypoxia-inducible factor 1 signaling pathway was involved in Txnip C247S-mediated cardioprotective mechanisms. CONCLUSION: Txnip is a cysteine-containing redox protein that robustly regulates the thioredoxin system via a disulfide bond-switching mechanism in adult cardiomyocytes. Our results provide the direct in vivo evidence that regulation of redox state by Txnip is a crucial component for myocardial homeostasis under ischemic stress.


Assuntos
Alelos , Substituição de Aminoácidos , Proteínas de Transporte/genética , Resistência à Doença/genética , Mutação , Infarto do Miocárdio/etiologia , Tiorredoxinas/genética , Trifosfato de Adenosina/metabolismo , Animais , Biomarcadores , Proteínas de Transporte/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Suscetibilidade a Doenças , Eletrocardiografia , Expressão Gênica , Glucose/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Transgênicos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Especificidade de Órgãos/genética , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/metabolismo , Ubiquitina Tiolesterase/metabolismo
8.
Crit Care ; 24(1): 592, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998762

RESUMO

Peripheral vascular catheterization (PVC) in pediatric patients is technically challenging. Ultrasound guidance has gained the most interest in perioperative and intensive care fields because it visualizes the exact location of small target vessels and is less invasive than other techniques. There have been a growing number of studies related to ultrasound guidance for PVC with or without difficult access in pediatric patients, and most findings have demonstrated its superiority to other techniques. There are various ultrasound guidance approaches, and a comprehensive understanding of the basics, operator experience, and selection of appropriate techniques is required for the successful utilization of this technique. This narrative review summarizes the literature regarding ultrasound-guided PVC principles, approaches, and pitfalls to improve its clinical performance in pediatric settings.


Assuntos
Cateterismo Periférico/métodos , Ultrassonografia de Intervenção/métodos , Cateterismo Periférico/instrumentação , Cateterismo Periférico/tendências , Criança , Humanos , Pediatria/métodos , Pediatria/tendências , Ultrassonografia de Intervenção/instrumentação , Ultrassonografia de Intervenção/tendências
10.
PLoS One ; 14(7): e0218797, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269049

RESUMO

MicroRNAs (miRNAs) are small RNA molecules that modulate gene and protein expression in hematopoiesis. Platelets are known to contain a fully functional miRNA machinery. While platelets used for transfusion are normally stored at room temperature, recent evidence suggests more favorable effects under a cold-storage condition, including higher adhesion and aggregation properties. Thus, we sought to determine whether functional differences in platelets are associated with the differential profiling of platelet miRNA expressions. To obtain the miRNA expression profile, next-generation sequencing was performed on human platelets obtained from 10 healthy subjects. The miRNAs were quantified after being stored in three different conditions: 1) baseline (before storage), 2) stored at 22°C with agitation for 72 h, and 3) stored at 4°C for 72 h. Following the identification of miRNAs by sequencing, the results were validated at the level of mature miRNAs from 18 healthy subjects, by using quantitative polymerase chain reaction (qPCR). Differential expression was observed for 125 miRNAs that were stored at 4°C and 9 miRNAs stored at 22°C as compared to the baseline. The validation study by qPCR confirmed that storage at 4°C increased the expression levels (fold change 95% CI) of mir-20a-5p (1.87, p<0.0001), mir-10a-3p (1.88, p<0.0001), mir-16-2-3p (1.54, p<0.01), and mir-223-5p (1.38, p<0.05), compared with those of the samples stored at 22°C. These results show that miRNAs correlate with platelet quality under specific storage conditions. The data indicate that miRNAs could be potentially used as biomarkers of platelet quality.


Assuntos
Biomarcadores/metabolismo , Plaquetas/metabolismo , MicroRNAs/genética , Transfusão de Plaquetas , Adulto , Temperatura Baixa , Feminino , Regulação da Expressão Gênica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Manejo de Espécimes
11.
Pediatr Crit Care Med ; 20(9): e410-e414, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31232853

RESUMO

OBJECTIVES: This study evaluated whether the dynamic needle tip positioning technique increased the success rate of ultrasound-guided peripheral venous catheterization in pediatric patients with a small-diameter vein compared with the static ultrasound-guided technique. DESIGN: Randomized controlled study. SETTING: Single institution, Osaka Women's and Children's Hospital. PATIENTS: The study population included 60 pediatric patients less than 2 years old who required peripheral venous catheterization in the PICU. INTERVENTIONS: Patients were randomly divided into the dynamic needle tip positioning (n = 30) or static group (n = 30). Each group received ultrasound-guided peripheral venous catheterization with or without dynamic needle tip positioning, respectively. The Fisher exact test, Kaplan-Meier curve plots, log-rank tests, and Mann-Whitney U test were used in the statistical analysis. MEASUREMENTS AND MAIN RESULTS: The first-attempt success rate was higher in the dynamic needle tip positioning group than in the static group (86.7% vs 60%; p = 0.039; relative risk = 1.44; 95% CI, 1.05-2.0). The overall success rate within 10 minutes was higher in the dynamic needle tip positioning group than in the static group (90% vs 63.3%; p = 0.03; relative risk = 1.42; 95% CI, 1.06-1.91). Significantly fewer attempts were made in the dynamic needle tip positioning group than in the static group (median [interquartile range, range] = 1 [1-1, 1-2] vs 1 [1-2, 1-3]; p = 0.013]). The median (interquartile range) catheterization times were 51.5 seconds (43-63 s) and 71.5 seconds (45-600 s) in the dynamic needle tip positioning and static groups, respectively (p = 0.01). CONCLUSIONS: Dynamic needle tip positioning increased the first-attempt and overall success rates of ultrasound-guided peripheral venous catheterization in pediatric patients less than 2 years old.


Assuntos
Cateterismo Periférico/métodos , Agulhas , Ultrassonografia de Intervenção/métodos , Cateterismo Periférico/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Masculino , Estudos Prospectivos
12.
J Cardiothorac Vasc Anesth ; 33(7): 1919-1925, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30638922

RESUMO

OBJECTIVE: Arterial catheterization for infants and small children is technically challenging. This study evaluated whether the dynamic needle tip positioning (DNTP) technique improved the success rate of ultrasound-guided radial artery catheterization in patients with a radial artery depth ≥4 mm compared with the conventional ultrasound-guided technique. DESIGN: Randomized controlled study. SETTING: Single institution, Osaka Women's and Children's Hospital. PARTICIPANTS: Patients (n = 40; age <3 years) with artery depth ≥4 mm. INTERVENTIONS: Patients were divided randomly into 2 groups. The DNTP group received ultrasound-guided radial artery catheterization with DNTP; the conventional group received catheterization without DNTP. MEASUREMENTS AND MAIN RESULTS: First-attempt success rates were 85% and 50% in the DNTP and conventional groups, respectively (p = 0.018; relative risk = 1.7; 95% CI: 1.06-2.73). Overall success rates within 10 minutes were 95% and 60% in the DNTP and conventional groups, respectively (p = 0.008; relative risk = 1.58; 95% CI: 1.09-2.3). Posterior wall puncture rates were 5% and 50% in the DNTP and conventional groups, respectively (p = 0.0014; relative risk = 0.1; 95% CI: 0.014-0.71). Significantly fewer attempts were made in the DNTP group (median = 1 v 1.5; p = 0.01). The median catheterization times were 38 seconds (34-55.5) and 149 seconds (49.5-600) in the DNTP and conventional groups, respectively (p = 0.0003). CONCLUSION: Dynamic needle tip positioning improved first-attempt and overall success rates of ultrasound-guided radial artery catheterization in pediatric patients with a radial artery depth ≥4 mm.


Assuntos
Cateterismo Periférico/métodos , Ultrassonografia de Intervenção/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Artéria Radial
13.
Ann Thorac Surg ; 107(1): e51-e53, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29890146

RESUMO

Anomalous origin of the coronary artery from the aortic arch associated with hypoplastic left heart syndrome is an extremely rare anomaly. Coronary anomalies can significantly deteriorate the clinical outcomes of hypoplastic left heart syndrome. We describe the case of a newborn with concomitant hypoplastic left heart syndrome and abnormal origin of the left coronary artery arising from the distal aortic arch.


Assuntos
Anomalias dos Vasos Coronários/cirurgia , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Aorta/anormalidades , Aorta/cirurgia , Anomalias dos Vasos Coronários/patologia , Evolução Fatal , Feminino , Parada Cardíaca/etiologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/patologia , Recém-Nascido , Complicações Intraoperatórias/etiologia , Ligadura , Procedimentos de Norwood , Cuidados Paliativos , Artéria Pulmonar/cirurgia
14.
Anesth Analg ; 129(2): 339-345, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30320649

RESUMO

BACKGROUND: Recombinant activated factor VII (rFVIIa) concentrate reduces allogeneic blood transfusions, but it may increase thromboembolic complications in complex cardiac surgery. The mixture of activated factor VII (FVIIa) and factor X (FX) (FVIIa/FX) (FVIIa:FX = 1:10) is a novel bypassing agent for hemophilia patients. We hypothesized that the combination of FX and FVIIa could improve thrombin generation (TG) in acquired multifactorial coagulation defects such as seen in cardiac surgery and conducted in vitro evaluation of FVIIa/FX in parallel with other coagulation factor concentrates using in vitro and in vivo diluted plasma samples. METHODS: Plasma samples were collected from 9 healthy volunteers and 12 cardiac surgical patients. We measured TG (Thrombinoscope) using in vitro 50% dilution plasma and in vivo dilution plasma after cardiopulmonary bypass, in parallel with thromboelastometry (ROTEM) and standard coagulation assays. In vitro additions of FVIIa/FX (0.35, 0.7, and 1.4 µg/mL, based on the FVIIa level), rFVIIa (1.4, 2.8, and 6.4 µg/mL), prothrombin complex concentrate (0.3 international unit), and 20% plasma replacement were evaluated. RESULTS: In diluted plasma, the addition of either FVIIa/FX or rFVIIa shortened the lag time and increased the peak TG, but the effect in lag time of FVIIa/FX at 0.35 µg/mL was more extensive than rFVIIa at 6.4 µg/mL. Prothrombin complex concentrate increased peak TG by increasing the prothrombin level but failed to shorten the lag time. No improvement in any of the TG variables was observed after 20% volume replacement with plasma. The addition of factor concentrates normalized prothrombin time/international normalized ratio but not with plasma replacement. In cardiac patients, similar patterns were observed on TG in post-cardiopulmonary bypass samples. FVIIa/FX shortened clotting time (CT) in a concentration-dependent manner on CT on thromboelastometry. Plasma replacement did not improve CT, but a combination of plasma and FVIIa/FX (0.35 µg/mL) more effectively shortened CT than FVIIa/FX alone. CONCLUSIONS: The combination of FVIIa and FX improved TG more efficiently than rFVIIa alone or plasma in dilutional coagulopathy models. The required FVIIa dose in FVIIa/FX was considerably lower than those reported during bypassing therapy in hemophilia patients (1.4-2.8 µg/mL). The combination of plasma could restore coagulation more efficiently compared to FVIIa/FX alone. Lesser FVIIa requirement to exert procoagulant activity may be favorable in terms of reducing systemic thromboembolic complications.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Coagulantes/farmacologia , Fator VIIa/farmacologia , Fator X/farmacologia , Hemodiluição/efeitos adversos , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Fatores de Coagulação Sanguínea/farmacologia , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Humanos , Masculino , Proteínas Recombinantes/farmacologia , Trombina/metabolismo , Fatores de Tempo
15.
Crit Care Med ; 46(8): e761-e767, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29742582

RESUMO

OBJECTIVES: Platelet defect mechanisms after cardiopulmonary bypass remain unclear. Our hypothesis microRNA expressions in circulating platelets significantly change between pre and post cardiopulmonary bypass, and consequent messenger RNA and protein expression level alterations cause postcardiopulmonary bypass platelet defect. DESIGN: Single-center prospective observational study. SETTING: Operating room of Kyoto Prefectural University of Medicine. PATIENTS: Twenty-five adult patients scheduled for elective cardiac surgeries under cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the initial phase, changes in microRNA expression between pre and post cardiopulmonary bypass underwent next generation sequencing analysis (10 patients). Based on the results, we focused on changes in mir-10b and mir-96, which regulate glycoprotein 1b and vesicle-associated membrane protein 8, respectively, and followed them until messenger RNA and protein syntheses (15 patients) using quantitative polymerase chain reaction and Western blotting. Seven microRNAs including mir-10b and mir-96 exhibited significant differences in the initial phase. In the subsequent phase, mir-10b-5p and mir-96-5p overexpressions were confirmed, and glycoprotein 1b and vesicle-associated membrane protein 8 messenger RNA levels were significantly decreased after cardiopulmonary bypass: fold differences (95% CI): mir-10b-5p: 1.35 (1.05-2.85), p value equals to 0.01; mir-96-5p: 1.59 (1.06-2.13), p value equals to 0.03; glycoprotein 1b messenger RNA: 0.46 (0.32-0.60), p value of less than 0.001; and vesicle-associated membrane protein messenger RNA: 0.70 (0.56-0.84), p value of less than 0.001. Glycoprotein 1b and vesicle-associated membrane protein 8 were also significantly decreased after cardiopulmonary bypass: glycoprotein 1b: 82.6% (71.3-93.8%), p value equals to 0.005; vesicle-associated membrane protein 8: 79.0% (70.7-82.3%), p value of less than 0.001. CONCLUSIONS: Expressions of several microRNAs in circulating platelets significantly changed between pre and post cardiopulmonary bypass. Overexpressions of mir-10b and mir-96 decreased glycoprotein 1b and vesicle-associated membrane protein 8 messenger RNA as well as protein, possibly causing platelet defect after cardiopulmonary bypass.


Assuntos
Plaquetas/metabolismo , Ponte Cardiopulmonar , MicroRNAs/biossíntese , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicoproteínas/biossíntese , Humanos , Masculino , Estudos Prospectivos , Proteínas R-SNARE/biossíntese , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase em Tempo Real
16.
J Cardiothorac Vasc Anesth ; 32(4): 1609-1614, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29395816

RESUMO

OBJECTIVE: Point-of-care (POC) devices allow for prothrombin time/international normalized ratio (PT/INR) testing in whole blood (WB) and timely administration of plasma or prothrombin complex concentrate during cardiopulmonary bypass surgery. This study evaluated the sensitivities of a new POC PT test, a dry-hematology method with heparin neutralization technology (DRIHEMATO PT-S [DRI PT-S]; A&T Corporation, Kanagawa, Japan), and compared it with other POC tests currently available. DESIGN: Prospective, observational study. SETTING: University hospital, single center. PARTICIPANTS: Healthy volunteers and warfarin-treated and cardiac surgical patients. MEASUREMENT AND MAIN RESULTS: In WB samples obtained from 6 healthy volunteers, PT-INR results of DRI PT-S were not affected by an in vitro addition of heparin <6.0 U/mL. In warfarin-treated samples (n = 88, PT/INR 0.98-3.87), PT-INR with DRI PT-S showed acceptable correlation with the laboratory method (r2 = 0.85, p < 0.001). In blood samples obtained from cardiac surgical patients (n = 72), heparin prolonged the PT/INR with the laboratory assay, dry-hematology method with non heparin neutralization technology (DRI PT), Coaguchek XS (Roche Diagnostics, Basel, Switzerland), and Hemochron Jr. (Accriva Diagnostics, Edison, NJ), but DRI PT-S was not affected by heparin anticoagulation. In nonheparinized samples, different methods between DRI PT-S and the laboratory method yielded acceptable correlations (r2 = 0.76, p < 0.0001). There was a moderate correlation between factor levels and the PT-INR with DRI PT-S (factor [F]II: r2 = 0.63, FVII: r2 = 0.47, FX: r2 = 0.67; p < 0.0001). CONCLUSIONS: This study demonstrated that PT/INR can be accurately assessed using the dry-hematology method in WB under therapeutic heparin levels. Currently available other POC PT/INR tests are affected by heparin, and thus they are not recommended for coagulation monitoring during cardiopulmonary bypass.


Assuntos
Ponte Cardiopulmonar/métodos , Monitorização Intraoperatória/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Tempo de Protrombina/métodos , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Ponte Cardiopulmonar/normas , Feminino , Humanos , Coeficiente Internacional Normatizado/métodos , Coeficiente Internacional Normatizado/normas , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/normas , Sistemas Automatizados de Assistência Junto ao Leito/normas , Estudos Prospectivos , Tempo de Protrombina/normas , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Adulto Jovem
17.
Pediatr Res ; 83(4): 866-873, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29281614

RESUMO

BackgroundChildren with cyanotic heart disease develop secondary erythrocytosis and thrombocytopenia via unknown mechanisms. Mature erythrocyte microRNAs may reflect clinical pathologies and cell differentiation processes pre-enucleation. This study evaluated erythrocyte microRNAs in children with cyanotic heart disease.MethodsErythrocyte microRNAs from children with cyanotic and acyanotic heart disease and without cardiac disease were quantified with Ion PGM System (n=10 per group). Differential expression was confirmed by quantitative PCR (qPCR; n=20 per group).ResultsMir-486-3p, mir-486-5p, and mir-155-5p increased in patients with cyanotic heart disease compared with those without heart disease: fold differences (95% confidence interval): mir-486-3p: 1.92 (1.14-3.23), P=0.011; mir-486-5p: 2.27 (1.41-3.65), P<0.001; and mir-155-5p: 1.44 (1.03-2.03), P=0.028. Mir-486-5p was increased, and let-7e-5p and mir-1260a were decreased in patients with acyanotic heart disease compared with those without heart disease: mir-486-5p: 1.66 (1.03-2.66), P=0.035; let-7e-5p: 0.66 (0.44-0.99), P=0.049; and mir-1260a: 0.53 (0.29-0.99), P=0.045.ConclusionSeveral microRNA levels changed in children with cyanotic and acyanotic heart disease. Mir-486-3p and -5p are associated with hematopoietic differentiation. Mir-486-3p regulates the erythroid vs. megakaryocyte lineage fate decision. Mir-155 is a hypoxia-inducible microRNA, whose overexpression inhibits megakaryocyte differentiation. Erythrocyte microRNA expression changes may contribute to erythrocytosis and thrombocytopenia in children with cyanotic heart disease.


Assuntos
Eritrócitos/metabolismo , Cardiopatias Congênitas/sangue , Cardiopatias/sangue , MicroRNAs/genética , Policitemia/sangue , Trombocitopenia/sangue , Pré-Escolar , Eritrócitos/citologia , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias/complicações , Humanos , Hipóxia/sangue , Lactente , Recém-Nascido , Masculino , Policitemia/complicações , Trombocitopenia/complicações
18.
JA Clin Rep ; 3(1): 10, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29492449

RESUMO

BACKGROUND: Subglottic stenosis can lead to life-threatening difficult tracheal intubation during general anesthesia. We report a case of difficult tracheal intubation in an 11-month-old female who had unrecognized subglottic stenosis. CASE PRESENTATION: The patient was scheduled for elective correction of a right accessory auricle. She was suspected of having first and second branchial arch syndrome. Preoperative physical examination was normal. Anesthesia was induced uneventfully using sevoflurane. It was not possible to pass size 4.0, 3.5, or 3.0 cuffed endotracheal tubes due to an advanced subglottic lesion. Subsequent successful intubation was achieved using a 3.0 uncuffed tube. Stridor was audible after extubation, and the patient required several days' treatment with dexamethasone to address respiratory distress. CONCLUSIONS: We encountered unrecognized subglottic stenosis that led to difficult tracheal intubation and post-extubation airway stenosis.

19.
Anesthesiology ; 125(4): 716-23, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27467290

RESUMO

BACKGROUND: The main cause of unsuccessful peripheral radial artery catheterization using traditional palpation is imprecisely locating the arterial center. The authors evaluated factors causing disparities between the arterial centers determined by palpation versus ultrasound. The authors applied them to create and test a novel catheterization training program. METHODS: The arterial central axis was determined by ultrasound and palpation in 350 adults. Potential independent predictors of disparity included sex, body mass index, pulse pressure, transverse arterial diameter, subcutaneous arterial depth, chronic hypertension, and experience as an anesthesiologist (less than 3 vs. greater than or equal to 3 yr). Using the results, the authors developed a radial artery catheterization training program. It was tested by enrolling 20 first-year interns, randomized to a training or control group. The time to successful insertion was the primary outcome measure. The success rate and time required for catheterization by palpation were evaluated in 100 adult patients per group. RESULTS: Independent predictors of central axis disparity were pulse pressure, subcutaneous radial artery depth, years of experience, and chronic hypertension. Training improved the catheterization time (training group 56 ± 2 s vs. control group 109 ± 2 s; difference -53 ± 3 s; 95% CI, -70 to -36 s; P < 0.0001) and total success rate (training group 83 of 100 attempts, 83%; 95% CI, 75 to 90 vs. control group 57 of 100, 57%; 95% CI, 47 to 66; odds ratio, 3.7; 95% CI, 2.7 to 5.1). CONCLUSIONS: Misjudging the central axis position of the radial artery is common with a weak pulse and/or deep artery. The authors' program, which focused on both these issues, shortened the time for palpation-guided catheterization and improved success.


Assuntos
Anestesiologistas/educação , Cateterismo Periférico/métodos , Internato e Residência/métodos , Palpação/estatística & dados numéricos , Artéria Radial/diagnóstico por imagem , Ultrassonografia de Intervenção/estatística & dados numéricos , Cateterismo Periférico/estatística & dados numéricos , Competência Clínica/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Case Rep Anesthesiol ; 2016: 6871565, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26989518

RESUMO

A 4-month-old female infant who weighed 3.57 kg with severe subglottic stenosis underwent tracheostomy under extracorporeal cardiopulmonary support. First, we set up extracorporeal cardiopulmonary support to the infant and then successfully intubated an endotracheal tube with a 2.5 mm inner diameter before tracheostomy by otolaryngologists. Extracorporeal cardiopulmonary support is an alternative for maintenance of oxygenation in difficult airway management in infants.

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