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1.
BMC Emerg Med ; 23(1): 85, 2023 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-37542224

RESUMO

BACKGROUND: In critically ill patients, healthy vitamin C levels are important to avoid an imbalance in reactive oxygen species. To achieve this, oxidative stress levels in emergency patients need to be accurately measured in real-time. However, normally, reactive oxygen/nitrogen species are short-lived, rendering measurement difficult; moreover, measurement of relatively stable antioxidants and other oxidative stress markers in real-time is challenging. Therefore, we used electron-spin resonance spectrometry (ESR) to assess vitamin C levels, clarify their relationship with patients' severity, and establish more effective vitamin C therapy in critically ill patients. METHODS: We studied 103 severely ill emergency patients and 15 healthy volunteers. Vitamin C radical (VCR/dimethyl sulfoxide [DMSO]) values were analyzed in arterial blood samples by ESR at admission and once daily thereafter during the acute recovery phase. Severity scores were calculated. The relationship between these scores and VCR/DMSO values and chronological changes in VCR/DMSO values were analyzed. RESULTS: Serum VCR/DMSO values were significantly lower in critically ill patients than in healthy volunteers (0.264 ± 0.014 vs. 0.935 ± 0.052, p < 0.05), particularly in the severe trauma group and the cardiopulmonary arrest/post-cardiac arrest syndrome group. VCR/DMSO values and various severity scores did not correlate at admission; however, they correlated with SOFA scores from days 2-6. VCR/DMSO values remained low from the first measurement day through Day 6 of illness. CONCLUSIONS: Vitamin C levels were low at admission, remained low with conventional nutritional support, and did not correlate with the initial patient's severity; however, they correlated with patients' severity after admission. Some patients had normal vitamin C levels. Therefore, vitamin C levels should be measured in real-time and supplemented if they are below normal levels. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Estado Terminal , Dimetil Sulfóxido , Humanos , Estado Terminal/terapia , Elétrons , Ácido Ascórbico , Análise Espectral
2.
Am J Physiol Lung Cell Mol Physiol ; 322(5): L647-L661, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35272486

RESUMO

Circadian amplitude enhancement has the potential to be organ protective but has not been studied in acute lung injury (ALI). Consistent light and dark cycles are crucial for the amplitude regulation of the circadian rhythm protein Period2 (PER2). Housing mice under intense instead of ambient light for 1 wk (light: dark cycle:14h:10h), we demonstrated a robust increase of pulmonary PER2 trough and peak levels, which is consistent with circadian amplitude enhancement. A search for the affected lung cell type suggested alveolar type 2 (ATII) cells as strong candidates for light induction of PER2. A head-to-head comparison of mice with cell-type-specific deletion of Per2 in ATII, endothelial, or myeloid cells uncovered a dramatic phenotype in mice with an ATII-specific deletion of Per2. During Pseudomonas aeruginosa-induced ALI, mice with Per2 deletion in ATII cells showed 0% survival, whereas 85% of control mice survived. Subsequent studies demonstrated that intense light therapy dampened lung inflammation or improved the alveolar barrier function during P. aeruginosa-induced ALI, which was abolished in mice with an ATII-specific deletion of Per2. A genome-wide mRNA array uncovered bactericidal/permeability-increasing fold-containing family B member 1 (BPIFB1) as a downstream target of intense light-elicited ATII-PER2 mediated lung protection. Using the flavonoid and PER2 amplitude enhancer nobiletin, we recapitulated the lung-protective and anti-inflammatory effects of light and BPIFB1, respectively. Together, our studies demonstrate that light-elicited amplitude enhancement of ATII-specific PER2 is a critical control point of inflammatory pathways during bacterial ALI.


Assuntos
Lesão Pulmonar Aguda , Proteínas Circadianas Period , Lesão Pulmonar Aguda/prevenção & controle , Animais , Ritmo Circadiano , Pulmão/metabolismo , Camundongos , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo
3.
J Clin Biochem Nutr ; 71(3): 185-190, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36447489

RESUMO

Landiolol, a highly cardioselective ultra-short-acting ß1-blocker, prevents perioperative atrial fibrillation associated with systemic inflammation and oxidative stress. We evaluated the direct scavenging activity of landiolol against multiple free radical species. Nine free radical species (hydroxyl, superoxide anion, ascorbyl, tert-butyl peroxyl, tert-butoxyl, singlet oxygen, 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and tyrosyl radicals) were directly quantified using an X-band ESR spectrometer with the spin-trapping method. IC50 and reaction rate constants were estimated from the dose-response curve for each free radical. Landiolol scavenged six of the free radical species examined: hydroxyl radical (IC50 = 0.76 mM, k landiolol = 1.4 × 10|10 M|-1 s|-1, p<0.001), superoxide anion (58 mM, 2.1 M|-1 s|-1, p = 0.044), tert-butoxyl radical (4.3 mM, k landiolol/k CYPMPO = 0.77, p<0.001), ascorbyl free radical (0.31 mM, p<0.001), singlet oxygen (0.69 mM, k landiolol/k 4-OH |TEMP = 2.9, p<0.001), and nitric oxide (15 mM, 1.7 × 10 M|-1 s|-1, p<0.001). This study is the first to report that landiolol dose-dependently scavenges multiple free radical species with different reaction rate constants. These results indicate the potential clinical application of landiolol as an antioxidative and anti-inflammatory agent in addition to its present clinical use as an anti-arrhythmic agent.

4.
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
5.
J Anesth ; 30(4): 583-90, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27137846

RESUMO

BACKGROUND: During epidural anesthesia, the catheter tip occasionally deviates from the epidural space into the intervertebral foramen, resulting in inadequate anesthesia. METHODS: During postoperative plain radiography, iohexol was injected via the epidural catheter to determine its position and to observe the spread of the material. After exclusion of seven patients with catheters that migrated into the subcutaneous area and 25 patients with no evidence of the contrast medium, 415 patients were evaluated. We retrospectively compared patients to determine whether the incidence of deviation into the intervertebral foramen differed between four types of epidural catheters. We also investigated the load applied to the catheter tip using a Shimadzu Autograph AG-X-500 N-111 universal testing machine. RESULTS: Deviation of the epidural catheter into the intervertebral foramen was observed in eight and 33 patients in the Hakko and Perifix Soft tip catheter groups, respectively. The incidence of deviation was higher in the Perifix Soft tip catheter group, and lower in the FlexTip Plus and Perifix FX catheter groups. A rapid increase was observed in the force exerted on the tips of the Hakko and Perifix Soft tip catheters, while the force transmitted to the tips of the FlexTip Plus and Perifix FX catheters gradually increased and then reached a plateau at a low level. CONCLUSIONS: The incidence of deviation was significantly lower with spiral-type catheters than with other types of catheters. This might be attributable to the gradual transmission of a lower level of force to the tip in spiral-type catheters.


Assuntos
Anestesia Epidural/métodos , Cateterismo/métodos , Catéteres , Adulto , Idoso , Meios de Contraste , Espaço Epidural , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos
7.
J Gastroenterol Hepatol ; 29(4): 749-56, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24236761

RESUMO

BACKGROUND AND AIM: Medical treatment for inflammatory bowel disease (IBD) requires chronic administration and causes side effects. Recently, anti-inflammatory effects of phototherapy were reported in animal models. The present study evaluated whether phototherapy improves dextran sulfate sodium (DSS)-induced colitis in a mouse model of IBD. METHODS: Mice were divided into four equal groups: Control, DSS, DSS + light low (LL), and DSS + light high (LH) groups. Normal fluorescent light intensity in the Control and DSS groups was 200 lux. Artificial light intensities were as follows: DSS + LL group, 1000 lux; DSS + LH group, 2500 lux. After administering phototherapy for 7 days, we evaluated disease activity index (DAI), histological score, colon length/weight, serum 1,25-dihydroxyvitamin D(3) level, and serum and colonic cytokines in the mice. RESULTS: DAI and histological scores were significantly lower in the DSS + LL group than in the DSS group (both, P < 0.05). Colon length and weight were significantly higher in the DSS + LL group than in the DSS group (both, P < 0.05). Serum interleukin (IL)-6, TNF-α, and IL-17 in the DSS + LL group were significantly lower, and serum and colonic IL-10 were significantly higher in the DSS + LL group than in the DSS group (all, P < 0.05). Serum 1,25-dihydroxyvitamin D(3) levels in the DSS + LH group were significantly increased compared with those in the DSS + LL and DSS groups. CONCLUSION: Artificial light phototherapy suppressed DSS-induced colitis in mice by suppression of pro-inflammatory cytokines and promotion of anti-inflammatory cytokines.


Assuntos
Colite/induzido quimicamente , Colite/terapia , Fototerapia/métodos , Animais , Biomarcadores/análise , Biomarcadores/sangue , Calcitriol/sangue , Colite/diagnóstico , Colite/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Mediadores da Inflamação/análise , Mediadores da Inflamação/sangue , Interleucina-10/análise , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
8.
JA Clin Rep ; 9(1): 53, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37612528

RESUMO

BACKGROUND: The anesthetic management of pregnant women with acute heart failure remains challenging with regard to maintaining the hemodynamic status of the mother and baby. The likelihood of decreased blood pressure is lower with remimazolam than with propofol. However, there is no report of general anesthesia with remimazolam for cesarean section. CASE PRESENTATION: The patient was a 34-year-old pregnant woman who was diagnosed with acute heart failure associated with infective endocarditis. We performed cesarean section under general anesthesia using remimazolam, with percutaneous cardiopulmonary support on standby. The mother's mean blood pressure was maintained above 65 mmHg during the surgery, without catecholamines or vasopressors. The infant's Apgar scores were 4 at 1 min and 7 at 5 min. CONCLUSION: Cesarean section was successfully performed under general anesthesia with remimazolam in a pregnant patient with acute heart failure. Further studies are needed to clarify the association between remimazolam and neonatal hypotension.

9.
JA Clin Rep ; 8(1): 86, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36260199

RESUMO

BACKGROUND: Remimazolam is an ultra-short-acting benzodiazepine anesthetic that is antagonized by flumazenil, and it is typically expected to be applied in anesthesia with the purpose of ensuring early postoperative recovery. We report a case of long-term delayed emergence with re-sedation even after three times of flumazenil administration. CASE PRESENTATION: A 71-year-old man was scheduled for a robotic-assisted laparoscopic radical prostatectomy for prostate cancer. We used remimazolam for anesthetic induction and maintenance. The intraoperative bispectral index (BIS) was 30-50. Flumazenil was administered as patient emergence was delayed after surgery; however, re-sedation was observed. This finding persisted till 12 h after surgery, and the patient awakened on postoperative day 2. CONCLUSIONS: Remimazolam is a short-acting anesthetic, but long-term delayed emergence with re-sedation may occur even after flumazenil administration. Anesthesia using remimazolam requires anesthesia management that takes into account the individual differences in sensitivity and metabolism, with BIS as the indicator.

10.
Middle East J Anaesthesiol ; 21(3): 375-83, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22428492

RESUMO

PURPOSE: In order to enhance postoperative recovery, preoperative consumption of carbohydrate (CHO) drinks has been used to suppress metabolic fluctuations. Trace elements such as zinc and copper are known to play an important role in postoperative recovery. Here, we examined the effects of preoperatively consuming a CHO drink containing zinc and copper. METHODS: Subjects were 122 elective surgery patients divided into two groups (overnight fasting and CHO groups); each group was further divided into morning or afternoon surgery groups. Subjects in the CHO group consumed 300 mL of a CHO drink the night before surgery, followed by 200 ml before morning surgery or 700 ml before afternoon surgery (> or =2 hours before anesthesia induction). Blood levels of glucose, nonesterified fatty acids (NEFA), retinol-binding protein, zinc, and copper were determined. RESULTS: One subject in the CHO group was excluded after refusing the drink. There were no adverse effects from the CHO drink. NEFA levels increased in the fasting groups. Although zinc levels increased in the CHO group immediately after anesthesia induction, no group differences were observed the day after surgery. CONCLUSION: Preoperative consumption of a CHO drink containing trace elements suppressed preoperative metabolic fluctuations without complications and prevented trace element deficiency. Further beneficial effects during the perioperative period can be expected by adding trace elements to CHO supplements.


Assuntos
Carboidratos da Dieta/farmacologia , Estado Nutricional/efeitos dos fármacos , Período Perioperatório , Oligoelementos/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia , Bebidas , Glicemia/análise , Pressão Sanguínea/fisiologia , Cobre/sangue , Procedimentos Cirúrgicos Eletivos , Jejum/fisiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Conteúdo Gastrointestinal , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Proteínas de Ligação ao Retinol/metabolismo , Adulto Jovem , Zinco/sangue
11.
Chronobiol Int ; 38(9): 1262-1273, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34034593

RESUMO

The cycle of day and night dominates life on earth. Therefore, almost all living organisms adopted a molecular clock linked to the light-dark cycles. It is now well established that this molecular clock is crucial for human health and wellbeing. Disruption of the molecular clockwork directly results in a myriad of disorders, including cardiovascular diseases. Further, the onset of many cardiovascular diseases such as acute myocardial infarction exhibits a circadian periodicity with worse outcomes in the early morning hours. Based on these observations, the research community became interested in manipulating the molecular clock to treat cardiovascular diseases. In recent years, several exciting discoveries of pharmacological agents or molecular mechanisms targeting the molecular clockwork have paved the way for circadian medicine's arrival in cardiovascular diseases. The current review will outline the most recent circadian therapeutic advances related to the circadian rhythm protein Period2 (PER2) to treat myocardial ischemia and summarize future research in the respective field.


Assuntos
Relógios Circadianos , Infarto do Miocárdio , Isquemia Miocárdica , Traumatismo por Reperfusão , Ritmo Circadiano , Humanos , Infarto do Miocárdio/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo
12.
Trends Mol Med ; 27(7): 627-629, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33980464

RESUMO

Angiopoietin-like 4 (ANGPTL4) is critical for regulating plasma lipids, and thus an attractive therapeutic target for cardiovascular diseases. Unfortunately, targeting ANGPTL4 results in a proinflammatory and ultimately lethal phenotype in animals. The serendipitous discovery of cardiac ANGPTL4 as a circadian protein reveals novel mechanistic insight and a solution for this therapeutic dilemma.


Assuntos
Proteína 4 Semelhante a Angiopoietina/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Regulação da Expressão Gênica , Terapia de Alvo Molecular , Proteína 4 Semelhante a Angiopoietina/genética , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Humanos
13.
Curr Pharm Des ; 26(34): 4330-4337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294028

RESUMO

BACKGROUND: We recently reported a role for the circadian rhythm protein Period 2 (PER2) in midazolam induced cognitive dysfunction. Based on previous studies showing a critical role for the adenosine A2B receptor (ADORA2B) in PER2 regulation, we hypothesized that hippocampal ADORA2B is crucial for cognitive function. METHODS: Midazolam treated C57BL/6J mice were analyzed for Adora2b hippocampal mRNA expression levels, and spontaneous T-maze alternation was determined in Adora2b-/- mice. Using the specific ADORA2B agonist BAY-60-6583 in midazolam treated C57BL/6J mice, we analyzed hippocampal Per2 mRNA expression levels and spontaneous T-maze alternation. Finally, Adora2b-/- mice were assessed for mRNA expression of markers for inflammation or cognitive function in the hippocampus. RESULTS: Midazolam treatment significantly downregulated Adora2b or Per2 mRNA in the hippocampus of C57BL/6J mice, and hippocampal PER2 protein expression or T-maze alternation was significantly reduced in Adora2b-/- mice. ADORA2B agonist BAY-60-6583 restored midazolam mediated reduction in spontaneous alternation in C57BL/6J mice. Analysis of hippocampal Tnf-α or Il-6 mRNA levels in Adora2b-/- mice did not reveal an inflammatory phenotype. However, C-fos, a critical component of hippocampus-dependent learning and memory, was significantly downregulated in the hippocampus of Adora2b-/- mice. CONCLUSION: These results suggest a role of ADORA2B in midazolam induced cognitive dysfunction. Further, our data demonstrate that BAY-60-6583 treatment restores midazolam induced cognitive dysfunction, possibly via increases of Per2. Additional mechanistic studies hint towards C-FOS as another potential underlying mechanism of memory impairment in Adora2b-/- mice. These findings suggest the ADORA2B agonist as a potential therapy in patients with midazolam induced cognitive dysfunction.


Assuntos
Disfunção Cognitiva , Receptor A2B de Adenosina , Adenosina , Animais , Hipocampo/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Midazolam , Receptor A2B de Adenosina/metabolismo
14.
PLoS One ; 15(12): e0244792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382840

RESUMO

Blood coagulation is central to myocardial ischemia and reperfusion (IR) injury. Studies on the light elicited circadian rhythm protein Period 2 (PER2) using whole body Per2-/- mice found deficient platelet function and reduced clotting which would be expected to protect from myocardial IR-injury. In contrast, intense light induction of PER2 protected from myocardial IR-injury while Per2 deficiency was detrimental. Based on these conflicting data, we sought to evaluate the role of platelet specific PER2 in coagulation and myocardial ischemia and reperfusion injury. We demonstrated that platelets from mice with tissue-specific deletion of Per2 in the megakaryocyte lineage (Per2loxP/loxP-PF4-CRE) significantly clot faster than platelets from control mice. We further found increases in infarct sizes or plasma troponin levels in Per2loxP/loxP-PF4-CRE mice when compared to controls. As intense light increases PER2 protein in human tissues, we also performed translational studies and tested the effects of intense light therapy on coagulation in healthy human subjects. Our human studies revealed that intense light therapy repressed procoagulant pathways in human plasma samples and significantly reduced the clot rate. Based on these results we conclude that intense light elicited PER2 has an inhibitory function on platelet aggregation in mice. Further, we suggest intense light as a novel therapy to prevent or treat clotting in a clinical setting.


Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/metabolismo , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteínas Circadianas Period/metabolismo , Fototerapia , Animais , Humanos , Luz , Masculino , Camundongos , Isquemia Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/sangue , Proteínas Circadianas Period/genética , Agregação Plaquetária/fisiologia , Proteômica
15.
Mil Med ; 185(9-10): e1542-e1550, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32515788

RESUMO

INTRODUCTION: Hemorrhagic shock is a primary injury amongst combat casualties. Hemorrhagic shock can lead to acute lung injury, which has a high mortality rate. Based on studies showing the role of intense light for organ-protection, we sought to evaluate if intense light pretreatment would be protective in a murine model of hemorrhagic shock lung. MATERIALS AND METHODS: After exposure to standard room light or to intense light (10 000 LUX), mice were hemorrhaged for 90 minutes to maintain a mean arterial pressure (MAP) of 30-35 mmHg. Mice were then resuscitated with their blood and a NaCl infusion at a rate of 0.2 ml/h over a 3-hour period. During resuscitation, blood pressure was recorded. At the end of resuscitation, bronchoalveolar lavage was analyzed for alveolar epithelial barrier function and inflammation. To get insight into the relevance of intense light for humans, we performed a proteomics screen for lung injury biomarkers in plasma from healthy volunteers following intense light therapy. RESULTS: We found that intense light pretreated mice had improved hemodynamics and significantly lower albumin, IL-6, and IL-8 levels in their bronchoalveolar lavage than controls. We further discovered that intense light therapy in humans significantly downregulated proinflammatory plasma proteins that are known to cause acute lung injury. CONCLUSIONS: Our data demonstrate that mice exposed to intense light before hemorrhagic shock lung have less lung inflammation and improved alveolar epithelial barrier function. We further show that intense light therapy downregulates lung injury promoting proteins in human plasma. Together, these data suggest intense light as a possible strategy to ameliorate the consequences of a hemorrhagic shock on lung injury.


Assuntos
Pulmão/fisiopatologia , Choque Hemorrágico , Animais , Modelos Animais de Doenças , Hemodinâmica , Inflamação , Camundongos , Ressuscitação , Choque Hemorrágico/complicações , Choque Hemorrágico/terapia
16.
Curr Pharm Des ; 25(19): 2199-2206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258066

RESUMO

BACKGROUND: Animal studies on cardiac arrest found that a combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction. Based on these findings, we hypothesized that esmololepinephrine combination therapy would be superior to a reported cardioprotective esmolol therapy alone in a mouse model of myocardial ischemia and reperfusion (IR) injury. METHODS: C57BL/6J mice were subjected to 60 min of myocardial ischemia and 120 min of reperfusion. Mice received either saline, esmolol (0.4 mg/kg/h), epinephrine (0.05 mg/kg/h), or esmolol combined with epinephrine (esmolol: 0.4 mg/kg/h or 0.8 mg/kg/h and epinephrine: 0.05 mg/kg/h) during reperfusion. After reperfusion, infarct sizes in the area-at-risk and serum cardiac troponin-I levels were determined. Hemodynamic effects of drugs infused were determined by measurements of heart rate (HR) and mean arterial blood pressure (MAP) via a carotid artery catheter. RESULTS: Esmolol during reperfusion resulted in robust cardioprotection (esmolol vs. saline: 24.3±8% vs. 40.6±3% infarct size), which was abolished by epinephrine co-administration (38.1±15% infarct size). Increasing the esmolol dose, however, was able to restore esmolol-cardioprotection in the epinephrine-esmolol (18.6±8% infarct size) co-treatment group with improved hemodynamics compared to the esmolol group (epinephrine-esmolol vs. esmolol: MAP 80 vs. 75 mmHg, HR 452 vs. 402 beats/min). CONCLUSION: These results confirm earlier studies on esmolol-cardioprotection from myocardial IR-injury and demonstrate that a dose optimized epinephrine-esmolol co-treatment maintains esmolol-cardioprotection with improved hemodynamics compared to esmolol treatment alone. These findings might have implications for current clinical practice in hemodynamically unstable patients suffering from myocardial ischemia.


Assuntos
Epinefrina/administração & dosagem , Isquemia Miocárdica/tratamento farmacológico , Propanolaminas/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio , Reprodutibilidade dos Testes
17.
J Vasc Access ; 20(1): 19-23, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29722288

RESUMO

INTRODUCTION:: Ultrasound-guided central venous catheter tip confirmation has a potential to precisely locate the central venous catheter, preventing its misplacement, using real-time guidance. This observational study sought to determine the accuracy of central venous catheter tip positioning via the external jugular vein via a supraclavicular fossa view under ultrasound guidance. METHODS:: In total, 77 patients scheduled for central venous catheter insertion via the right external jugular vein were enrolled. The depth of central venous catheter insertion was determined by advancing the tip of the guidewire to the junction of the superior vena cava and right pulmonary artery, using a right supraclavicular fossa view ultrasound method. We determined the reference insertion depth to the carina using a postoperative chest x-ray photograph method. We then compared insertion depths obtained by the ultrasound and x-ray photograph methods and body-height formula. RESULTS:: In total, 62 patients were able to advance the guidewire and underwent ultrasound-guided central venous catheter insertion. In four patients, we corrected for misplaced guidewires. According to Bland-Altman plots, the insertion depth was 0.88 cm shorter for the ultrasound method (95% limits of agreement, -1.66 to 3.41 cm) and 0.90 cm shorter for the formulaic method (95% limits of agreement, -2.77 to 4.56 cm), compared with the x-ray photograph method. The x-ray photograph method had significantly positive correlations with the ultrasound (r = 0.73) and formulaic methods (r = 0.27). CONCLUSION:: A right supraclavicular fossa view improves the accuracy of central venous catheter tip positioning and prevents central venous catheter misplacement via the right external jugular vein.


Assuntos
Cateterismo Venoso Central/instrumentação , Cateterismo Venoso Central/métodos , Cateteres de Demora , Cateteres Venosos Centrais , Veias Jugulares/diagnóstico por imagem , Ultrassonografia de Intervenção , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Cateterismo Venoso Central/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Flebografia , Valor Preditivo dos Testes , Punções
18.
Cell Rep ; 28(6): 1471-1484.e11, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390562

RESUMO

Consistent daylight oscillations and abundant oxygen availability are fundamental to human health. Here, we investigate the intersection between light-sensing (Period 2 [PER2]) and oxygen-sensing (hypoxia-inducible factor [HIF1A]) pathways in cellular adaptation to myocardial ischemia. We demonstrate that intense light is cardioprotective via circadian PER2 amplitude enhancement, mimicking hypoxia-elicited adenosine- and HIF1A-metabolic adaptation to myocardial ischemia under normoxic conditions. Whole-genome array from intense light-exposed wild-type or Per2-/- mice and myocardial ischemia in endothelial-specific PER2-deficient mice uncover a critical role for intense light in maintaining endothelial barrier function via light-enhanced HIF1A transcription. A proteomics screen in human endothelia reveals a dominant role for PER2 in metabolic reprogramming to hypoxia via mitochondrial translocation, tricarboxylic acid (TCA) cycle enzyme activity regulation, and HIF1A transcriptional adaption to hypoxia. Translational investigation of intense light in human subjects identifies similar PER2 mechanisms, implicating the use of intense light for the treatment of cardiovascular disease.


Assuntos
Relógios Circadianos , Endotélio Vascular/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Isquemia Miocárdica/terapia , Fototerapia , Transcrição Gênica/efeitos da radiação , Adulto , Animais , Hipóxia Celular , Linhagem Celular , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Proteínas Circadianas Period/efeitos da radiação
19.
Radiat Med ; 26(9): 519-25, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19030959

RESUMO

PURPOSE: The aim of this study was to evaluate the technical success, complications, and effectiveness of re-radiofrequency (re-RF) ablation for recurrent lung tumors previously treated with RF ablation. MATERIALS AND METHODS: Reenlargement at the site of ablation seen on follow-up computed tomography (CT) is defined as local progression. CT-guided re-RF ablation was performed during 11 treatment sessions (mean tumor size 2.6 cm diameter) in 10 patients. The treated lesions consisted of five recurrences of primary lung cancer and six metastatic lung tumors from the esophagus (n = 2), bladder (n = 2), kidney (n = 1), and colon (n = 1). RESULTS: At 3 of the 11 treatment sessions there were no relapses; at 8 of the 11 sessions local progression was seen at a median of 7 months (range 3-17 months). The local progression rate was significantly higher for tumors > 2.5 cm (P < 0.05). Minor complications included pneumothorax not requiring drainage (n = 3), subcutaneous emphysema (n = 1), and self-limited hemoptysis (n = 2). CONCLUSION: Re-RF ablation for lung tumors was feasible without any major complications. Although our study comprised only a few cases with a short follow-up period, patients with re-RF ablation were at higher risk of local progression.


Assuntos
Ablação por Cateter , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Tomógrafos Computadorizados , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter/efeitos adversos , Progressão da Doença , Feminino , Seguimentos , Hemoptise/etiologia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Pneumotórax/etiologia , Radiografia Intervencionista/métodos , Retratamento , Estudos Retrospectivos , Fatores de Risco , Enfisema Subcutâneo/etiologia , Resultado do Tratamento
20.
Masui ; 57(4): 443-6, 2008 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-18416200

RESUMO

Septic shock is an adverse clinical condition resulting in multiple organ failure from global tissue hypoxia. The importance of initial treatment is widely recognized. Thus, guidelines for septic shock recommend early goal-directed therapy (EGDT) during the first six hours of treatment. Central venous oxygen saturation monitoring is useful to maintain adequate tissue oxygen delivery. A newly developed central venous oximetry catheter (PreSep Oximetery Catheter, Edwards Lifesciences) allows continuous and easy monitoring of central venous oxygen saturation. This report shows the usefulness of this catheter in a patient who developed septic shock during an emergency operation for perforated bowel. By using EGDT perioperatively with continuous central venous oximetry, multiple organ failure might be successfully avoided.


Assuntos
Cateterismo Venoso Central , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/terapia , Monitorização Intraoperatória/métodos , Oximetria/métodos , Oxigênio/sangue , Choque Séptico/diagnóstico , Choque Séptico/terapia , Idoso , Colo Sigmoide/cirurgia , Emergências , Humanos , Perfuração Intestinal/complicações , Perfuração Intestinal/cirurgia , Cuidados Intraoperatórios , Complicações Intraoperatórias/etiologia , Masculino , Insuficiência de Múltiplos Órgãos/prevenção & controle , Choque Séptico/etiologia , Resultado do Tratamento , Veias
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