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1.
J Pers Med ; 13(9)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37763148

RESUMO

This single-center retrospective exploratory analysis evaluated the effects of sugammadex compared with neostigmine on postoperative recovery in patients with myasthenia gravis (MG) who underwent video-assisted thoracoscopic surgery (VATS)-thymectomy. This retrospective study included 180 patients with MG, aged >18 years, who received sugammadex (sugammadex group, n = 83) or neostigmine-glycopyrrolate (neostigmine group, n = 88) after VATS-thymectomy between November 2007 and December 2020. Inverse probability of treatment weighting (IPTW) adjustment was performed to balance the baseline characteristics between the two groups. The primary outcome was the length of postoperative hospital stay, and the secondary outcomes were the incidence of postoperative mortality and complications, as well as the postoperative extubation and reintubation rates, in the operating room after VATS-thymectomy; the outcomes were compared between the two groups. After IPTW adjustment, the sugammadex group showed a significantly shorter median postoperative hospital stay than the neostigmine group (4 (2, 4) vs. 5 (3, 6) days, respectively; p = 0.003). There were no significant differences between the two groups in the incidences of postoperative complications (including postoperative myasthenic crisis, nerve palsy, atelectasis, and pleural effusion). Patients with MG following VATS-thymectomy who received sugammadex showed a significantly shorter postoperative hospital stay than those who received neostigmine.

2.
Eur J Anaesthesiol ; 40(9): 691-698, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37455644

RESUMO

BACKGROUND: The effect of hypercarbia on lung oxygenation during thoracic surgery remains unclear. OBJECTIVE: To investigate the effect of hypercarbia on lung oxygenation during one-lung ventilation in patients undergoing thoracic surgery and evaluate the incidence of postoperative pulmonary complications. DESIGN: Prospective randomised controlled trial. SETTING: A tertiary university hospital in the Republic of Korea from November 2019 to December 2020. PATIENTS: Two hundred and ninety-seven patients with American Society of Anaesthesiologists physical status II to III, scheduled to undergo elective lung resection surgery. INTERVENTION: Patients were randomly assigned to Group 40, 50, or 60. An autoflow ventilation mode with a lung protective ventilation strategy was applied to all patients. Respiratory rate was adjusted to maintain a partial pressure of arterial carbon dioxide of 40 ±â€Š5 mmHg in Group 40, 50 ±â€Š5 mmHg in Group 50 and 60 ±â€Š5 mmHg in Group 60 during one-lung ventilation and at the end of surgery. MAIN OUTCOME MEASURES: The primary outcome was the arterial oxygen partial pressure/fractional inspired oxygen ratio after 60 min of one-lung ventilation. RESULTS: Data from 262 patients were analysed. The partial pressure/fractional inspired oxygen ratio was significantly higher in Group 50 and Group 60 than in Group 40 (269.4 vs. 262.9 vs. 214.4; P  < 0.001) but was not significantly different between Group 50 and Group 60. The incidence of postoperative pulmonary complications was comparable among the three groups. CONCLUSION: Permissive hypercarbia improved lung oxygenation during one-lung ventilation without increasing the risk of postoperative pulmonary complications or the length of hospital stay. TRIAL REGISTRATION: NCT04175379.


Assuntos
Ventilação Monopulmonar , Cirurgia Torácica , Humanos , Ventilação Monopulmonar/efeitos adversos , Estudos Prospectivos , Pulmão/cirurgia , Respiração Artificial/efeitos adversos , Hipercapnia , Oxigênio , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Volume de Ventilação Pulmonar
3.
Br J Anaesth ; 130(1): e106-e118, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35995638

RESUMO

BACKGROUND: Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear. METHODS: In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H2O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively. RESULTS: The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H2O in the driving pressure group vs 9.2 cm H2O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H2O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H2O-1; P<0.001) and Pao2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group. CONCLUSIONS: In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation. CLINICAL TRIAL REGISTRATION: NCT04260451.


Assuntos
Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Respiração com Pressão Positiva/efeitos adversos , Pulmão , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Volume de Ventilação Pulmonar
4.
Mol Ther ; 30(4): 1523-1535, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35077861

RESUMO

Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we showed that a lectibody consisting of the high-mannose glycan-binding lectin Avaren and human immunoglobulin G1 (IgG1) Fc (AvFc) selectively recognizes a range of cell lines derived from lung, breast, colon, and blood cancers at nanomolar concentrations. Binding of AvFc to the non-small cell lung cancer (NSCLC) cell lines A549 and H460 was characterized in detail. Co-immunoprecipitation proteomics analysis revealed that epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) are among the lectibody's common targets in these cells. AvFc blocked the activation of EGFR and IGF1R by their respective ligands in A549 cells and inhibited the migration of A549 and H460 cells upon stimulation with EGF and IGF1. Furthermore, AvFc induced potent Fc-mediated cytotoxic effects and significantly restricted A549 and H460 tumor growth in severe combined immunodeficiency (SCID) mice. Immunohistochemistry analysis of primary lung tissues from NSCLC patients demonstrated that AvFc preferentially binds to tumors over adjacent non-tumor tissues. Our findings provide evidence that increased abundance of high-mannose glycans in the glycocalyx of cancer cells can be a druggable target, and AvFc may provide a new tool to probe and target this tumor-associated glycobiomarker.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Manose , Camundongos , Polissacarídeos/farmacologia
6.
J Clin Med ; 9(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244659

RESUMO

Placing a double-lumen endobronchial tube (DLT) in an appropriate position to facilitate lung isolation is essential for thoracic procedures. The novel ANKOR DLT is a DLT developed with three cuffs with a newly added carinal cuff designed to prevent further advancement by being blocked by the carina when the cuff is inflated. In this prospective study, the direction and depth of initial placement of ANKOR DLT were compared with those of conventional DLT. Patients undergoing thoracic surgery (n = 190) with one-lung ventilation (OLV) were randomly allocated into either left-sided conventional DLT group (n = 95) or left-sided ANKOR DLT group (n = 95). The direction and depth of DLT position were compared via fiberoptic bronchoscopy (FOB) after endobronchial intubation between the groups. There was no significant difference in the number of right mainstem endobronchial intubations between the two groups (p = 0.468). The difference between the initial depth of DLT placement and the target depth confirmed by FOB was significantly lower in the ANKOR DLT group than in the conventional DLT group (1.8 ± 1.8 vs. 12.9 ± 9.7 mm; p < 0.001). In conclusion, the ANKOR DLT facilitated its initial positioning at the optimal depth compared to the conventional DLT.

7.
Korean J Anesthesiol ; 73(3): 194-204, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32098009

RESUMO

Protective ventilation is a prevailing ventilatory strategy these days and is comprised of small tidal volume, limited inspiratory pressure, and application of positive end-expiratory pressure (PEEP). However, several retrospective studies recently suggested that tidal volume, inspiratory pressure, and PEEP are not related to patient outcomes, or only related when they influence the driving pressure. Therefore, this review introduces the concept of driving pressure and looks into the possibility of driving pressure-guided ventilation as a new ventilatory strategy, especially in thoracic surgery where postoperative pulmonary complications are common, and thus, lung protection is of utmost importance.


Assuntos
Respiração com Pressão Positiva/métodos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Volume de Ventilação Pulmonar/fisiologia , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos
8.
FASEB J ; 33(12): 13527-13545, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31560862

RESUMO

Cholera toxin B subunit (CTB) exhibits broad-spectrum biologic activity upon mucosal administration. Here, we found that a recombinant CTB containing an endoplasmic reticulum (ER) retention motif (CTB-KDEL) induces colon epithelial wound healing in colitis via the activation of an unfolded protein response (UPR) in colon epithelial cells. In a Caco2 cell wound healing model, CTB-KDEL, but not CTB or CTB-KDE, facilitated cell migration via interaction with the KDEL receptor, localization in the ER, UPR activation, and subsequent TGF-ß signaling. Inhibition of the inositol-requiring enzyme 1/X-box binding protein 1 arm of UPR abolished the cell migration effect of CTB-KDEL, indicating that the pathway is indispensable for the activity. CTB-KDEL's capacity to induce UPR and epithelial restitution or wound healing was corroborated in a dextran sodium sulfate-induced acute colitis mouse model. Furthermore, CTB-KDEL induced a UPR, up-regulated wound healing pathways, and maintained viable crypts in colon explants from patients with inflammatory bowel disease (IBD). In summary, CTB-KDEL exhibits unique wound healing effects in the colon that are mediated by its localization to the ER and subsequent activation of UPR in epithelial cells. The results provide implications for a novel therapeutic approach for mucosal healing, a significant unmet need in IBD treatment.-Royal, J. M., Oh, Y. J., Grey, M. J., Lencer, W. I., Ronquillo, N., Galandiuk, S., Matoba, N. A modified cholera toxin B subunit containing an ER retention motif enhances colon epithelial repair via an unfolded protein response.


Assuntos
Toxina da Cólera/farmacologia , Colite/tratamento farmacológico , Retículo Endoplasmático/metabolismo , Células Epiteliais/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Resposta a Proteínas não Dobradas , Cicatrização/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Adulto , Idoso , Motivos de Aminoácidos , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana/toxicidade , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Adulto Jovem
9.
Medicine (Baltimore) ; 98(33): e16869, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415423

RESUMO

RATIONALE: Precise lung isolation technique with visual confirmation is essential for thoracic surgeries to create a safe and clear surgical field. However, in certain situations, such as when patients have massive pulmonary secretion or when the fiberoptic bronchoscopy (FOB) is not applicable, lung isolation has been performed blindly. PATIENT CONCERN: A 52-year-old woman, whose airway was unable to visualize with FOB due to massive pulmonary secretion, was presented for bilateral sequential lung transplantation. Extracorporeal membranous oxygenation, tracheostomy, and mechanical ventilation were applied to the patient for 39 days preoperatively as a bridge for lung transplantation. DIAGNOSIS: Patient was diagnosed with an idiopathic pulmonary fibrosis and obesity. INTERVENTION: Initially, height-based blind positioning with a conventional double-lumen endobronchial tube (DLT) failed to ventilate the patient properly, and the confirmation of DLT positioning with FOB was impossible due to massive pulmonary secretion. Therefore, a novel DLT (ANKOR DLT) that has one more cuff, located at a point between the distal opening of the tracheal lumen and the starting point of bronchial cuff, than conventional DLT was used for the lung isolation in the patient. OUTCOMES: After the completion of lung graft, FOB finding showed that the ANKOR DLT was optimally positioned at the tracheobronchial tree of the patient, and its depth was 2.5 cm shallower than that of the conventional tube. LESSONS: ANKOR DLT would be a feasible choice to achieve successful blind lung isolation when the use of FOB is impossible to achieve the optimal lung isolation.


Assuntos
Broncoscopia/instrumentação , Fibrose Pulmonar Idiopática/cirurgia , Intubação Intratraqueal/métodos , Ventilação Monopulmonar/métodos , Desenho de Equipamento , Feminino , Humanos , Fibrose Pulmonar Idiopática/complicações , Transplante de Pulmão/instrumentação , Transplante de Pulmão/métodos , Pessoa de Meia-Idade , Obesidade/complicações
10.
J Clin Med ; 8(5)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126111

RESUMO

Although the application of positive end-expiratory pressure (PEEP) can alter cardiopulmonary physiology during one-lung ventilation (OLV), these changes have not been clearly elucidated. This study assessed the effects of different levels of PEEP on biventricular function, as well as pulmonary oxygenation during OLV. Thirty-six lung cancer patients received one PEEP combination of six sequences, consisting of 0 (PEEP_0), 5 (PEEP_5), and 10 cmH2O (PEEP_10), using a crossover design during OLV. The ratio of arterial oxygen partial pressure to inspired oxygen fraction (P/F ratio), systolic and diastolic echocardiographic parameters were measured at 20 min after the first, second, and third PEEP. P/F ratio at PEEP_5 was significantly higher compared to PEEP_0 (p = 0.014), whereas the P/F ratio at PEEP_10 did not show significant differences compared to PEEP_0 or PEEP_5. Left ventricular ejection fraction (LV EF) and right ventricular fractional area change (RV FAC) at PEEP_10 (EF, p < 0.001; FAC, p = 0.001) were significantly lower compared to PEEP_0 or PEEP_5. RV E/E' (p = 0.048) and RV myocardial performance index (p < 0.001) at PEEP_10 were significantly higher than those at PEEP_0 or PEEP_5. In conclusion, increasing PEEP to 10 cmH2O decreased biventricular function, especially on RV function, with no further improvement on oxygenation compared to PEEP 5 cmH2O during OLV.

11.
Int J Med Sci ; 15(10): 961-968, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013436

RESUMO

Background: The efficacy of dexamethasone plus palonosetron for postoperative nausea and vomiting (PONV) prophylaxis is not firmly established. This randomized, double-blind, controlled study evaluated whether the combination was superior to palonosetron alone in preventing PONV in patients receiving intravenous patient-controlled analgesia (IV-PCA) after upper extremity surgery. Methods: A total of 202 patients undergoing upper extremity surgery were randomly assigned to group P (palonosetron alone) or group PD (palonosetron plus dexamethasone). Group P patients received palonosetron 0.075 mg and normal saline 1.6 mL; group PD patients received palonosetron 0.075 mg and dexamethasone 8 mg. In both groups, palonosetron was added to the IV-PCA opioid infusion, which was continued for 48 h postoperatively. Incidence and severity of nausea, incidence of vomiting, rescue antiemetic requirements, pain intensity, and rescue analgesic requirements were evaluated for 72 h postoperatively. Quality of recovery was assessed using the quality of recovery-15 (QoR-15) questionnaire. Results: The incidence of PONV was significantly lower in group PD than in group P at 0-48 h postoperatively (61.5% vs 77.1%; p = 0.019). Severity of nausea at 0-6 h postoperatively was significantly less in group PD compared with group P (none/mild/moderate/severe: 49/22/15/10 vs. 36/16/25/19, p = 0.008). The incidence of vomiting and rescue antiemetic requirements were similar between groups. Pain intensity was significantly less in group PD than in group P at 0-48 h and 48-72 h postoperatively. Global QoR-15 was similar 24 h postoperatively between groups. Conclusions: Dexamethasone-palonosetron combination therapy reduced PONV incidence and postoperative pain in patients receiving opioid-based analgesia after upper extremity surgery.


Assuntos
Analgésicos Opioides/efeitos adversos , Antieméticos/administração & dosagem , Dexametasona/administração & dosagem , Náusea/tratamento farmacológico , Palonossetrom/administração & dosagem , Vômito/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estudos Prospectivos , Vômito/induzido quimicamente
12.
Anesth Analg ; 126(4): 1353-1361, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29324496

RESUMO

BACKGROUND: The optimal regional technique for analgesia and improved quality of recovery after video-assisted thoracic surgery (a procedure associated with considerable postoperative pain) has not been established. The main objective in this study was to compare quality of recovery in patients undergoing serratus plane block (SPB) with either ropivacaine or normal saline on the first postoperative day. Secondary outcomes were analgesic outcomes, including postoperative pain intensity and opioid consumption. METHODS: Ninety patients undergoing video-assisted thoracic surgery were randomized to receive ultrasound-guided SPB with 0.4 mL/kg of either 0.375% ropivacaine (SPB group) or normal saline (control group) after anesthetic induction. The primary outcome was the 40-item Quality of Recovery (QoR-40) score at 24 hours after surgery. The QoR-40 questionnaire was completed by patients the day before surgery and on postoperative days 1 and 2. Pain scores, opioid consumption, and adverse events were assessed for 2 days postoperatively. RESULTS: Eighty-five patients completed the study: 42 in the SPB group and 43 in the control group. The global QoR-40 scores on both postoperative days 1 and 2 were significantly higher in the SPB group than in the control group (estimated mean difference 8.5, 97.5% confidence interval [CI], 2.1-15.0, and P = .003; 8.5, 97.5% CI, 2.0-15.1, and P = .004, respectively). The overall mean difference between the SPB and control groups was 8.5 (95% CI, 3.3-13.8; P = .002). Pain scores at rest and opioid consumption were significantly lower up to 6 hours after surgery in the SPB group than in the control group. Cumulative opioid consumption was significantly lower up to 24 hours postoperatively in the SPB group. CONCLUSIONS: Single-injection SPB with ropivacaine enhanced the quality of recovery for 2 days postoperatively and improved postoperative analgesia during the early postoperative period in patients undergoing video-assisted thoracic surgery.


Assuntos
Anestésicos Locais/administração & dosagem , Músculos Intermediários do Dorso/inervação , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Ropivacaina/administração & dosagem , Cirurgia Torácica Vídeoassistida , Ultrassonografia de Intervenção , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Anestésicos Locais/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/efeitos adversos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Recuperação de Função Fisiológica , República da Coreia , Ropivacaina/efeitos adversos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
J Anesth ; 31(1): 18-24, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27817156

RESUMO

PURPOSE: The role of dexmedetomidine on left ventricular function is ambiguous. We analyzed pressure-volume loops to investigate whether dexmedetomidine has a myocardial depressive effect. METHODS: Thirty-two Sprague-Dawley rats were anesthetized and a pressure-volume loop catheter was advanced into the left ventricle. Rats were divided into four groups (n = 8 each). The control group received a 10-min infusion of 0.1 ml of normal saline, and the other three groups received 1.0 (Dex1.0 group) , 2.5 (Dex2.5 group), and 5.0 µg/kg (Dex5.0 group) dexmedetomidine in a similar fashion to the control group. Steady-state hemodynamic parameters were recorded. The inferior vena cava was occluded intermittently to assess preload-independent indices. RESULTS: Compared with the control group, changes in the Dex1.0 group were insignificant. In the Dex2.5 group, only the systolic blood pressure was higher (vs control, P = 0.03), and other parameters were insignificant. The Dex5.0 group exhibited a lower heart rate, higher systolic blood pressure, higher arterial elastance (vs control, all P < 0.001), and unaltered cardiac output. The Dex5.0 group showed steeper slopes of end-systolic pressure increment and end-systolic pressure-volume relationship than the control, Dex1.0, and Dex2.5 groups (all P < 0.001). Slopes of end-diastolic pressure decrement and end-diastolic pressure-volume relationship did not differ among groups. CONCLUSION: Dexmedetomidine had no direct myocardial depressant effect in the rat heart in doses that are similar to those encountered under clinical conditions. Dexmedetomidine did not significantly alter the ability of the heart to cope with bradycardia and greatly increased afterload. Their potentially negative impact on cardiac output was effectively attenuated by improved myocardial contractility and preserved diastolic function in healthy subjects.


Assuntos
Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Calibragem , Débito Cardíaco/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Relação Dose-Resposta a Droga , Elasticidade , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Infusões Intravenosas , Masculino , Ratos , Ratos Sprague-Dawley
14.
Amino Acids ; 49(3): 695-704, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27438265

RESUMO

Aging is associated with increased cardiomyocyte loss, left-ventricular hypertrophy, and the accumulation of extracellular matrix, which results in declining cardiac function. The role of the matrix crosslinking enzyme, tissue transglutaminase (TG2), in age-related myocardial stiffness, and contractile function remains incompletely understood. In this study, we examined the role of TG2 in cardiac function, and determined whether TG2 inhibition can prevent age-associated changes in cardiac function. Male Fisher rats (18-month-old) were administered the transglutaminase inhibitor cystamine (study group) or saline (age-matched controls) for 12 weeks via osmotic mini-pumps. Cardiac function was determined by echocardiography and invasive pressure-volume loops. Rat hearts were dissected out, and TG2 expression, activity, and S-nitrosation were determined. Young (6-month-old) males were used as controls. TG2 activity significantly increased in the saline-treated but not in the cystamine-treated aging rat hearts. TG2 expression also increased with age and was unaltered by cystamine treatment. Aged rats showed increased left ventricular (LV) end-systolic dimension and a decrease in fractional shortening compared with young, which was not affected by cystamine. However, cystamine treatment preserved the preload-independent index of LV filling pressure and restored end-diastolic pressure, end-diastolic pressure-volume relationships, and arterial elastance toward young. An increase in TG2 activity contributes to age-associated increase in diastolic stiffness, thereby contributing to age-associated diastolic dysfunction. TG2 may thus represent a novel target for age-associated diastolic heart failure.


Assuntos
Envelhecimento/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Ventrículos do Coração/enzimologia , Hipertrofia Ventricular Esquerda/enzimologia , Miócitos Cardíacos/enzimologia , Transglutaminases/metabolismo , Envelhecimento/patologia , Animais , Pressão Sanguínea , Cistamina/farmacologia , Ecocardiografia , Elasticidade , Inibidores Enzimáticos/farmacologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/enzimologia , Matriz Extracelular/patologia , Proteínas de Ligação ao GTP/antagonistas & inibidores , Proteínas de Ligação ao GTP/genética , Expressão Gênica , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Bombas de Infusão Implantáveis , Masculino , Miocárdio/enzimologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Proteína 2 Glutamina gama-Glutamiltransferase , Ratos , Ratos Endogâmicos F344 , Transglutaminases/antagonistas & inibidores , Transglutaminases/genética
15.
Medicine (Baltimore) ; 95(7): e2854, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26886651

RESUMO

Video-assisted thoracoscopic surgery (VATS) has been known to be a stressful event for patients, and dexmedetomidine is known to attenuate surgery-induced sympathetic responses and potentiate analgesia in perioperative periods. The present was designed to evaluate the effects of intraoperative dexmedetomidine administration on the quality of recovery (QoR) and pulmonary function after VATS. Patients with lung cancer undergoing VATS were randomized to Dex group (loading of 1.0 µg/kg for 20 minutes before the termination of surgery, n = 50) or Control group (comparable volume of normal saline, n = 50). The QoR-40 questionnaire assesses postoperative recovery and validates the overall surgical and general anesthesia outcomes. The QoR-40 scores, forced expiratory volume for 1 second (FEV1) on postoperative day (POD) 1 and 2, and emergence agitation were evaluated. The global QoR-40 score (162.3 ±â€Š17.8 vs 153.3 ±â€Š18.7, P = 0.016 on POD 1; 174.3 ±â€Š16.0 vs 166.8 ±â€Š16.7, P = 0.028 on POD 2) and FEV1 (2.1 ±â€Š0.4 vs 1.9 ±â€Š0.5 L, P = 0.034 on POD 1; 2.2 ±â€Š0.5 vs 2.0 ±â€Š0.4 L, P = 0.030 on POD 2) were significantly higher in the Dex group compared with the Control group on POD1 and POD 2. The score of emergence agitation was lower in the Dex group compared with the Control group (3 [2-5] vs 5 [3-7], P < 0.001). The number of patients indicating severe emergence agitation was shorter in the Dex group than Control group (0 [0%] vs 7 [14%], P = 0.048). The length of hospital stay was significantly shorter (6.7 [3-9] vs 8.4 [4-9] days, P = 0.045) in the Dex group compared with the Control group. Intraoperative dexmedetomidine administration improved QoR, postoperative pulmonary function, and emergence agitation in patients undergoing VATS. Consequently, intraoperative dexmedetomidine administration could improve postoperative outcomes and reduced the length of hospital stay in patients undergoing VATS.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Dexmedetomidina/administração & dosagem , Pulmão/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Cirurgia Torácica Vídeoassistida , Idoso , Feminino , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Medicine (Baltimore) ; 95(6): e2805, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26871847

RESUMO

Dexmedetomidine is a commonly used sedative and adjuvant agent to general anesthesia. The present was designed to evaluate the effects of dexmedetomidine on myocardial function by using tissue Doppler echocardiography during general anesthesia in patients with diastolic dysfunction.Forty patients undergoing orthostatic surgery with ejection fraction preserved diastolic dysfunction grade 2 or 3 were randomly allocated to the Control and Dex group (n = 20, each). In the Dex group, dexmedetomidine was given as an initial loading dose of 1.0 µg/kg over 10 minutes followed by a maintenance dose of 0.5 µg/kg/h. The ratio of peak early diastolic transmitral or transtricuspid inflow velocity to early diastolic mitral or tricuspid annular velocity (LV or RV E/e') and left or right ventricular myocardial performance index (LV or RV MPI) were measured at before and after the administration dexmedetomidine or saline.The Dex group showed significant decrease of heart rate (P = 0.038), and increase of mean blood pressure (P < 0.001), LV E/e' (P = 0.025), and LV MPI (P < 0.001) compared to those of the Control group on a linear mixed model analysis. Also, the Dex group showed significant increase of RV E/e' (P < 0.001) and RV MPI (P = 0.028) compared to those of the Control group.Intraoperative dexmedetomidine administration during general anesthesia was appeared to deteriorate biventricular function in patients with diastolic dysfunction. We suggest careful consideration and a need for reducing dosage when administrating dexmedetomidine in patients with diastolic dysfunction.


Assuntos
Anestesia Geral , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Dexmedetomidina/farmacologia , Ecocardiografia Doppler , Coração/efeitos dos fármacos , Coração/fisiologia , Hipnóticos e Sedativos/farmacologia , Cuidados Intraoperatórios , Idoso , Diástole , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos
17.
J Clin Monit Comput ; 30(6): 995-1002, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26719298

RESUMO

Hemodynamic instability in the beach chair position (BCP) may lead to adverse outcomes. Cardiac preload optimization is a prerequisite to improve hemodynamics. We evaluated the clinical usefulness of dynamic indices for the prediction of fluid responsiveness in BCP patients under general anesthesia. Forty-two patients in the BCP under mechanical ventilation received colloids at 6 ml/kg for 10 min. Stroke volume variation (SVV), pulse pressure variation (PPV), pleth variability index (PVI), and hemodynamic data were measured before and after the fluid challenge. Patients were considered responders to volume expansion if the stroke volume index increased by ≥15 %. The areas under receiver operating characteristic curves for SVV, PPV and PVI were 0.83, 0.81 and 0.74, respectively (p < 0.05), with the corresponding optimal cut-off values of 12, 15 and 10 %. SVV, PPV and PVI can be used to predict fluid responsiveness in the BCP under mechanical ventilation.


Assuntos
Hidratação/métodos , Hemodinâmica , Pletismografia/métodos , Postura , Idoso , Anestesia , Área Sob a Curva , Artroscopia/métodos , Pressão Sanguínea , Ecocardiografia/métodos , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Estudos Prospectivos , Curva ROC , Respiração Artificial , Sensibilidade e Especificidade , Volume Sistólico
18.
Yonsei Med J ; 57(1): 238-46, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26632407

RESUMO

PURPOSE: Oxidative stress during CO2 pneumoperitoneum is reported to be associated with decreased bioactivity of nitric oxide (NO). However, the changes in endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and arginase during CO2 pneumoperitoneum have not been elucidated. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomized into three groups. After anesthesia induction, the abdominal cavities of the rats of groups intra-abdominal pressure (IAP)-10 and IAP-20 were insufflated with CO2 at pressures of 10 mm Hg and 20 mm Hg, respectively, for 2 hours. The rats of group IAP-0 were not insufflated. After deflation, plasma NO was measured, while protein expression levels and activity of eNOS, iNOS, arginase (Arg) I, and Arg II were analyzed with aorta and lung tissue samples. RESULTS: Plasma nitrite concentration and eNOS expression were significantly suppressed in groups IAP-10 and IAP-20 compared to IAP-0. While expression of iNOS and Arg I were comparable between the three groups, Arg II expression was significantly greater in group IAP-20 than in group IAP-0. Activity of eNOS was significantly lower in groups IAP-10 and IAP-20 than in group IAP-0, while iNOS activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. Arginase activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. CONCLUSION: The activity of eNOS decreases during CO2 pneumoperitoneum, while iNOS activity is significantly increased, a change that contributes to increased oxidative stress and inflammation. Moreover, arginase expression and activity is increased during CO2 pneumoperitoneum, which seems to act inversely to the NO system.


Assuntos
Aorta/fisiologia , Arginase/antagonistas & inibidores , Inflamação/prevenção & controle , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pneumoperitônio/complicações , Animais , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Inflamação/etiologia , Injeções Subcutâneas , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Masculino , Óxido Nítrico/metabolismo , Pneumoperitônio/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
19.
Eur J Anaesthesiol ; 33(4): 275-82, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26716866

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a risk factor that increases the incidence of postoperative cardiopulmonary morbidity and mortality after lung resection. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has been reported previously to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction. OBJECTIVE: The objective is to determine whether dexmedetomidine improves oxygenation and lung mechanics in patients with moderate COPD during lung cancer surgery. DESIGN: A randomised, double-blinded, placebo-controlled study. SETTING: Single university hospital. PARTICIPANTS: Fifty patients scheduled for video-assisted thoracoscopic surgery who had moderate COPD. Patients were randomly allocated to a control group or a Dex group (n = 25 each). INTERVENTIONS: In the Dex group, dexmedetomidine was given as an initial loading dose of 1.0  µg  kg(-1) over 10  min followed by a maintenance dose of 0.5  µg  kg(-1)  h(-1) during OLV while the control group was administered a comparable volume of 0.9% saline. Data were measured at 30  min (DEX-30) and 60  min (DEX-60) after dexmedetomidine or saline administration during OLV. MAIN OUTCOME MEASURES: The primary outcome was the effect of dexmedetomidine on oxygenation. The secondary outcome was the effect of dexmedetomidine administration on postoperative pulmonary complications. RESULTS: Patients in the Dex group had a significantly higher PaO2/FIO2 ratio (27.9 ±â€Š5.8 vs. 22.5 ±â€Š8.4 and 28.6 ±â€Š5.9 vs. 21.0 ±â€Š9.9 kPa, P < 0.05), significantly lower dead space ventilation (19.2 ±â€Š8.5 vs. 24.1 ±â€Š8.1 and 19.6 ±â€Š6.7 vs. 25.3 ±â€Š7.8%, P < 0.05) and higher dynamic compliance at DEX-30 and DEX-60 (P = 0.0001 and P = 0.0184) compared with the control group. In the Dex group, the PaO2/FIO2 ratio in the postoperative period was significantly higher (P = 0.022) and the incidence of ICU admission was lower than in the control group. CONCLUSION: Dexmedetomidine administration may provide clinically relevant benefits by improving oxygenation and lung mechanics in patients with moderate COPD undergoing lung cancer surgery. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT 02185430.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Broncodilatadores/administração & dosagem , Dexmedetomidina/administração & dosagem , Neoplasias Pulmonares/cirurgia , Pulmão/efeitos dos fármacos , Pulmão/cirurgia , Pneumonectomia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Mecânica Respiratória/efeitos dos fármacos , Cirurgia Torácica Vídeoassistida , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Idoso , Broncodilatadores/efeitos adversos , Dexmedetomidina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Hospitais Universitários , Humanos , Pulmão/fisiopatologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , República da Coreia , Índice de Gravidade de Doença , Cirurgia Torácica Vídeoassistida/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
Mol Plant ; 9(4): 501-13, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-26712506

RESUMO

Rhizosphere acidification is essential for iron (Fe) uptake into plant roots. Plasma membrane (PM) H(+)-ATPases play key roles in rhizosphere acidification. However, it is not fully understood how PM H(+)-ATPase activity is regulated to enhance root Fe uptake under Fe-deficient conditions. Here, we present evidence that cytochrome b5 reductase 1 (CBR1) increases the levels of unsaturated fatty acids, which stimulate PM H(+)-ATPase activity and thus lead to rhizosphere acidification. CBR1-overexpressing (CBR1-OX) Arabidopsis thaliana plants had higher levels of unsaturated fatty acids (18:2 and 18:3), higher PM H(+)-ATPase activity, and lower rhizosphere pH than wild-type plants. By contrast, cbr1 loss-of-function mutant plants showed lower levels of unsaturated fatty acids and lower PM H(+)-ATPase activity but higher rhizosphere pH. Reduced PM H(+)-ATPase activity in cbr1 could be restored in vitro by addition of unsaturated fatty acids. Transcript levels of CBR1, fatty acids desaturase2 (FAD2), and fatty acids desaturase3 (FAD3) were increased under Fe-deficient conditions. We propose that CBR1 has a crucial role in increasing the levels of unsaturated fatty acids, which activate the PM H(+)-ATPase and thus reduce rhizosphere pH. This reaction cascade ultimately promotes root Fe uptake.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Citocromo-B(5) Redutase/metabolismo , Ferro/metabolismo , Arabidopsis/citologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Transporte Biológico , Membrana Celular/metabolismo , Citocromo-B(5) Redutase/genética , Espaço Extracelular/metabolismo , Ácidos Graxos Insaturados/metabolismo , Regulação da Expressão Gênica de Plantas , Mutação , ATPases Translocadoras de Prótons/metabolismo , Rizosfera , Sementes/metabolismo , Solo/química , Solubilidade , Regulação para Cima
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