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Background: Saline is still the most widely used storage and rinsing solution for vessel grafts during cardiac surgery despite knowing evidence of its negative influence on the human endothelial cell function. Aim of this study was to assess the effect of DuraGraft©, an intraoperative graft treatment solution, on human saphenous vein segments and further elaborate the vasoprotective effect on rat aortic segments in comparison to saline. Methods: Human Saphenous vein (HSV) graft segments from patients undergoing aortocoronary bypass surgery (n = 15), were randomized to DuraGraft© (n = 15) or saline (n = 15) solution before intraoperative storage. Each segment was divided into two subsegmental parts for evaluation. These segments as well as rat aortic segments stored in DuraGraft© underwent assessment of vascular function in a multichamber isometric myograph system in comparison to Krebs-Henseleit solution (KHS), a physiologic organ buffer solution. Results: Potassium-Chloride (KCL)-induced contraction depicted a tendency towards increase when treated with DuraGraft© compared to saline preservation of HSV segments (23.02 ± 14.77 vs 14.44 ± 9.13 mN, p = 0.0571). Vein segments preserved with DuraGraft© showed a significant improvement of endothelium-dependent vasorelaxation in response to cumulative concentrations of bradykinin compared to saline treated segments (p < 0.05). Rat aortic segments stored in saline showed significantly impaired vasoconstriction (3.59 ± 4.20, p < 0.0001) and vasorelaxation when compared to KHS and DuraGraft© (p < 0.0001). Conclusions: DuraGraft© demonstrated a favorable effect on graft relaxation and contraction indicating preservation of vascular endothelial function. Clinical Trial Registration Number: NCT04614077.
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Thoracic aortic aneurysm (TAA) is an age-related and life-threatening vascular disease. Telomere shortening is a predictor of age-related diseases, and its progression is associated with premature vascular disease. The aim of the present work was to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of TAA. We analyzed healthy and aortic aneurysm specimens (215 samples) for telomere length (TL), chronic DNA damage, and resulting changes in cellular homeostasis, focusing on senescence and apoptosis. Compared with healthy thoracic aorta (HTA), patients with tricuspid aortic valve (TAV) showed telomere shortening with increasing TAA size, in contrast to genetically predisposed bicuspid aortic valve (BAV). In addition, TL was associated with chronic hypoxia and telomeric DNA damage and with the induction of senescence-associated secretory phenotype (SASP). TAA-TAV specimens showed a significant difference in SASP-marker expression of IL-6, NF-κB, mTOR, and cell-cycle regulators (γH2AX, Rb, p53, p21), compared to HTA and TAA-BAV. Furthermore, we observed an increase in CD163+ macrophages and a correlation between hypoxic DNA damage and the number of aortic telocytes. We conclude that chronic hypoxia is associated with telomeric DNA damage and the induction of SASP in a diseased aortic wall, promising a new therapeutic target.
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Aneurisma da Aorta Torácica , Doença da Válvula Aórtica Bicúspide , Doenças das Valvas Cardíacas , Humanos , Doenças das Valvas Cardíacas/metabolismo , Fenótipo Secretor Associado à Senescência , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/complicações , Valva Aórtica/metabolismoRESUMO
BACKGROUND: Arterial tortuosity is linked to a higher risk of adverse clinical events after transfemoral transcatheter aortic valve replacement (TF-TAVR). Currently, there are no assessment tools that can quantify this variable in three-dimensional space. This study investigated the impact of novel scoring methods of iliofemoral tortuosity on access and bleeding complications after TF-TAVR. METHODS: The main access vessel was assessed between the aortoiliacal and femoral bifurcation in preoperative multislice computed tomography scans of 240 consecutive patients undergoing TF-TAVR. Tortuosity was assessed by three methods: largest single angle, sum of all angles, and iliofemoral tortuosity (IFT) score [((true vessel length/ideal vessel length)-1)*100]. The primary study endpoint was a composite of access and bleeding complications. The secondary study endpoints were 30-day mortality and long-term survival. RESULTS: Among 240 patients, only the IFT score demonstrated a good positive correlation with the composite primary endpoint of access and bleeding complications (P = 0.031). A higher incidence of access and bleeding complications was found in patients with a higher IFT score (56 [36.8%] vs 17 [19.3%]; P = 0.003). In a multivariate logistic regression analysis, only the IFT score was a significant predictor of the primary endpoint (OR: 2.11; 95% CI: 1.09-4.05; P = 0.026). CONCLUSION: Vascular tortuosity is an underestimated risk factor during TF-TAVR. The IFT score is a valuable tool in risk stratification before TF-TAVR, predicting periprocedural access and bleeding complications.
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Aorta/diagnóstico por imagem , Artéria Femoral/diagnóstico por imagem , Artéria Ilíaca/diagnóstico por imagem , Complicações Intraoperatórias/epidemiologia , Hemorragia Pós-Operatória/epidemiologia , Substituição da Valva Aórtica Transcateter/métodos , Lesões do Sistema Vascular/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/epidemiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Masculino , Tomografia Computadorizada MultidetectoresRESUMO
BACKGROUND: We investigated the impact of an elevated plasma volume status (PVS) in patients undergoing TAVI on early clinical safety and mortality and assessed the prognostic utility of PVS for outcome prediction. MATERIALS AND METHODS: We retrospectively calculated the PVS in 652 patients undergoing TAVI between 2009 and 2018 at two centres. They were then categorized into two groups depending on their preoperative PVS (PVS ≤-4; n = 257 vs PVS>-4; n = 379). Relative PVS was derived by subtracting calculated ideal (iPVS = c × weight) from actual plasma volume (aPVS = (1 - haematocrit) × (a + (b × weight in kg)). RESULTS: The need for renal replacement therapy (1 (0.4%) vs 17 (4.5%); P = .001), re-operation for noncardiac reasons (9 (3.5%) vs 32 (8.4%); P = .003), re-operation for bleeding (9 (3.5%) vs 27 (7.1%); P = .037) and major bleeding (14 (5.4%) vs 37 (9.8%); P = .033) were significantly higher in patients with a PVS>-4. The composite 30-day early safety endpoint (234 (91.1%) vs 314 (82.8%); P = .002) confirms that an increased preoperative PVS is associated with a worse overall outcome after TAVI. CONCLUSIONS: An elevated PVS (>-4) as a marker for congestion is associated with significantly worse outcome after TAVI and therefore should be incorporated in preprocedural risk stratification.
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The mitochondrial ATP synthase (F(1)F(o) complex) is an evolutionary conserved multimeric protein complex that synthesizes the main bulk of cytosolic ATP, but the regulatory mechanisms of the subunits are only poorly understood in plants. In yeast, the δ-subunit links the membrane-embedded F(o) part to the matrix-facing central stalk of F(1). We used genetic interference and an inhibitor to investigate the molecular function and physiological impact of the δ-subunit in Arabidopsis thaliana. Delta mutants displayed both male and female gametophyte defects. RNA interference of delta resulted in growth retardation, reduced ATP synthase amounts, and increased alternative oxidase capacity and led to specific long-term increases in Ala and Gly levels. By contrast, inhibition of the complex using oligomycin triggered broad metabolic changes, affecting glycolysis and the tricarboxylic acid cycle, and led to a successive induction of transcripts for alternative respiratory pathways and for redox and biotic stress-related transcription factors. We conclude that (1) the δ-subunit is essential for male gametophyte development in Arabidopsis, (2) a disturbance of the ATP synthase appears to lead to an early transition phase and a long-term metabolic steady state, and (3) the observed long-term adjustments in mitochondrial metabolism are linked to reduced growth and deficiencies in gametophyte development.
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Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/genética , Células Germinativas Vegetais/crescimento & desenvolvimento , Mitocôndrias/enzimologia , ATPases Mitocondriais Próton-Translocadoras/genética , Arabidopsis/embriologia , Arabidopsis/enzimologia , Arabidopsis/fisiologia , Respiração Celular , Cotilédone/embriologia , Cotilédone/enzimologia , Cotilédone/genética , Cotilédone/fisiologia , Regulação para Baixo/genética , Flores/embriologia , Flores/enzimologia , Flores/genética , Flores/fisiologia , Perfilação da Expressão Gênica , Células Germinativas Vegetais/citologia , Meristema/embriologia , Meristema/enzimologia , Meristema/genética , Meristema/fisiologia , Metaboloma , Mitocôndrias/genética , ATPases Mitocondriais Próton-Translocadoras/antagonistas & inibidores , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Mutagênese Insercional , Oligomicinas/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Oxidativo , Fenótipo , Infertilidade das Plantas , Plântula/embriologia , Plântula/enzimologia , Plântula/genética , Plântula/fisiologia , Transdução de Sinais , TranscriptomaRESUMO
The plant respiratory chain contains several pathways which bypass the energy-conserving electron transport complexes I, III and IV. These energy bypasses, including type II NAD(P)H dehydrogenases and the alternative oxidase (AOX), may have a role in redox stabilization and regulation, but current evidence is inconclusive. Using RNA interference, we generated Arabidopsis thaliana plants simultaneously suppressing the type II NAD(P)H dehydrogenase genes NDA1 and NDA2. Leaf mitochondria contained substantially reduced levels of both proteins. In sterile culture in the light, the transgenic lines displayed a slow growth phenotype, which was more severe when the complex I inhibitor rotenone was present. Slower growth was also observed in soil. In rosette leaves, a higher NAD(P)H/NAD(P)⺠ratio and elevated levels of lactate relative to sugars and citric acid cycle metabolites were observed. However, photosynthetic performance was unaffected and microarray analyses indicated few transcriptional changes. A high light treatment increased AOX1a mRNA levels, in vivo AOX and cytochrome oxidase activities, and levels of citric acid cycle intermediates and hexoses in all genotypes. However, NDA-suppressing plants deviated from the wild type merely by having higher levels of several amino acids. These results suggest that NDA suppression restricts citric acid cycle reactions, inducing a shift towards increased levels of fermentation products, but do not support a direct association between photosynthesis and NDA proteins.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , FMN Redutase/genética , Proteínas Mitocondriais/genética , NADH NADPH Oxirredutases/genética , Interferência de RNA , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Sequência de Bases , Western Blotting , Ciclo do Ácido Cítrico/efeitos dos fármacos , Ciclo do Ácido Cítrico/efeitos da radiação , Transporte de Elétrons/efeitos dos fármacos , Transporte de Elétrons/efeitos da radiação , FMN Redutase/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Isoenzimas/genética , Isoenzimas/metabolismo , Luz , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Proteínas Mitocondriais/metabolismo , Dados de Sequência Molecular , NADH NADPH Oxirredutases/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotenona/farmacologia , Homologia de Sequência do Ácido Nucleico , Técnicas de Cultura de Tecidos , Transcriptoma/efeitos dos fármacos , Transcriptoma/efeitos da radiação , Desacopladores/farmacologiaRESUMO
BACKGROUND: The timing of treatment for chronic aortic valve regurgitation (AR), especially in asymptomatic patients, is gaining attention since less invasive strategies have become available. The aim of the present study was to evaluate left ventricular reverse remodeling after aortic valve replacement (AVR) for severe AR. METHODS: Patients (n = 25) who underwent surgical AVR for severe AR with left ventricular ejection fraction (LVEF) less than 55% were included in this study. Preprocedural and follow-up clinical and echocardiographic measurements of LVEF and left ventricular (LV) diameters were retrospectively analyzed. RESULTS: Mean LVEF increased significantly following surgical AVR (p < 0.0001). LV diameters showed a clear regression (p = 0.0088). Younger patients and those receiving a mechanical valve tended to have less improved LVEF on follow-up than patients over 60 years or the ones who were implanted with a biological prosthesis (p = 0.0239 and p = 0.069, respectively). Gender had no effect on the degree of LVEF improvement (p = 0.4908). CONCLUSIONS: We demonstrated significant LV reverse remodeling following AVR for AR. However, more data are needed on LV functional and geometrical improvement comparing the different types of valve prostheses to provide an optimal treatment strategy.
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OBJECTIVES: The objective of this study was to enhance the efficiency of aortic arch replacement through the development of a novel frozen elephant trunk (FET) prosthesis with an endovascular side branch for left subclavian artery (LSA) connection. After successful pre-clinical testing, the feasibility and safety of implementing this innovative prosthesis in human subjects were investigated. METHODS: Between September 2020 and September 2021, 4 patients (mean age 67) with conditions such as penetrating ulcer, non A-non B aortic dissection and chronic arch aneurysm underwent surgery utilizing the customized device. Surgeries were performed under high moderate hypothermia (27°C), employing bilateral selective antegrade cerebral perfusion (SACP) and distal aortic perfusion. Anastomosis of the FET prosthesis with the aortic arch occurred in zone 1, followed by separate reimplantation of the left common carotid artery and the brachiocephalic artery. RESULTS: All patients were discharged in good clinical condition. The mean aortic cross-clamp, antegrade selective cerebral perfusion and distal aortic perfusion times were 111, 71 and 31 min, respectively. Endovascular extension of the side branch for the LSA was required in all cases to prevent endoleak formation. One patient received a stent graft extension at the end of the operation, while 2 others underwent the procedure during their hospital stay. One patient was diagnosed with an endoleak at the first follow-up after 3 months, and endoleak sealing was achieved via the brachial artery with an extension stent graft. CONCLUSIONS: Preliminary clinical outcomes suggest that the newly designed FET prosthesis shows promise in simplifying total arch replacement. These initial findings provide a foundation for planned clinical studies to further assess the effectiveness of this modified surgical hybrid graft, with particular attention to the length and diameter of the LSA sidearm.
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Implante de Prótese Vascular , Prótese Vascular , Procedimentos Endovasculares , Artéria Subclávia , Humanos , Artéria Subclávia/cirurgia , Idoso , Masculino , Implante de Prótese Vascular/métodos , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/efeitos adversos , Pessoa de Meia-Idade , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/instrumentação , Dissecção Aórtica/cirurgia , Desenho de Prótese , Aneurisma da Aorta Torácica/cirurgia , Feminino , Aorta Torácica/cirurgiaRESUMO
Objective: Cardiac surgery is known to activate a cascade of inflammatory mediators leading to a systemic inflammatory response. Hemadsorption (HA) devices such as CytoSorb® have been postulated to mitigate an overshooting immune response, which is associated with increased morbidity and mortality, and thus improve outcome. We aimed to investigate the effect of CytoSorb® on interleukin (IL)-6 levels in patients undergoing complex cardiac surgery in comparison to a control group. Methods: A total of 56 patients (28 CytoSorb®, 28 control) undergoing acute and elective cardiac surgery between January 2020 and February 2021 at the Department of Cardiac and Vascular Surgery, Clinic Floridsdorf, Vienna, were retrospectively analyzed. The primary endpoint was the difference in IL-6 levels between the CytoSorb® and control group. Secondary endpoint was periprocedural mortality. Results: CytoSorb®, installed in the bypass circuit, had no significant effect on IL-6 levels. IL-6 peaked on the first postoperative day (HA: 775.3 ± 838.4 vs. control: 855.5 ± 1,052.9â pg/ml, p = 0.856). In total, three patients died in the HA group, none in the control (logistic regression model, p = 0.996). Patients with an increased Euroscore II of 7 or more showed a reduced IL-6 response compared to patients with an Euroscore II below 7 (178.3 ± 63.1â pg/ml vs. 908.6 ± 972.6â pg/ml, p-value = 0.00306). Conclusions: No significant reduction of IL-6 levels or periprocedural mortality through intraoperative HA with CytoSorb® in patients undergoing cardiac surgery was observed. However, this study was able to show a reduced immunologic response in patients with a high Euroscore II. The routine application of CytoSorb® in cardiac surgery to reduce inflammatory mediators has to be scrutinized in future prospective randomized studies.
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The frozen elephant trunk (FET) technique is an established therapeutic option in the treatment of complex aortic diseases. We report our long-term clinical outcomes after FET repair. A total of 187 consecutive patients underwent FET repair at our department between 8/2005 and 3/2023. Indications included acute and chronic aortic dissections and thoracic aneurysms. Endpoints included operative morbidity and mortality, long-term survival, and the need for reinterventions. Operative mortality, spinal cord injury and permanent stroke rates were: 9.6%, 2.7% and 10.2%, respectively. At five years, overall survival was 69.9 ± 3.9% and freedom from aortic-related death was 82.5 ± 3.0%, whereas at ten years, overall survival was 53.0 ± 5.5% and freedom from aortic-related death was 75.8 ± 4.8%. Sixty-one reinterventions on the thoracic aorta were necessary. Freedom from secondary interventions at ten years was 44.7 ± 6.4% overall (63.1 ± 10.0% for acute dissections, 40.8 ± 10.3% for chronic dissections and 28.9 ± 13.1% for aneurysms, respectively). The high reintervention rate for chronic dissections and for aneurysms is related to the pre-existing aortic pathology. Late aortic growth of untreated segments with potentially fatal outcome occurs even after ten years, so careful annual follow-up is mandatory in this patient cohort.
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BACKGROUND: To assess quality of life and unmet needs after stroke, patient-reported outcome measures (PROMs) have gained increasing attention. However, patients' perspectives on assessing PROMs remain unclear, potentially hindering implementation into clinical practice. Therefore, this study explored patients' preferences on assessing PROMs after ischemic stroke. METHODS: A paper-based questionnaire was sent to stroke survivors treated at the Department of Neurology, University of Leipzig, Germany. Health-related quality of life (HRQoL, EQ-5D-5L) and preferences regarding different aspects of data collection to assess PROMs were investigated and linked to socio-demographic and medical characteristics. RESULTS: 158 persons were contacted and 80 replies were subsequently analyzed. Mean age was 70.16 years and mean HRQoL was 68.79 (visual analogue scale with a theoretical maximum of 100). Participants showed positive attitudes towards PROMs as they saw potential to improve care of other patients (n = 66/79; 83.54%) or to improve their own situation (n = 53/74; 71.62%). Participants preferred an annual interview after stroke (n = 39/80; 48.75%) and would preferably spend 15-30 min (n = 41/79; 51.90%) to answer a written survey (n = 69/80; 86.25%). The initially treating clinic was preferred as initiator of such surveys (n = 43/79; 54.43%). Stratification revealed that participants with more than 1 h of daily digital media usage preferred email as way of communication. CONCLUSIONS: For the first time, this study showed individual preferences on assessing PROMs after ischemic stroke, focusing on the way, time interval, duration, and initiation site of surveys. These insights might help to successfully implement PROMs after stroke and subsequently detect unmet needs and deficits in stroke care.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Idoso , Internet , Qualidade de Vida , Acidente Vascular Cerebral/terapia , Sobreviventes , Medidas de Resultados Relatados pelo PacienteRESUMO
By understanding stroke as a chronic disease, aftercare becomes increasingly important. For developing aftercare programs, the patients' perspective regarding, for example, stroke-related symptoms and interactions with the healthcare system is necessary. Records from a local stroke pilot program were used to extract relevant topics from the patients' perspective, as mentioned during a phone call two months after hospital discharge. Data from 157 patients with ischemic stroke or transient ischemic attack (TIA) were included. "Rehabilitation" was mentioned by 67.5% of patients, followed by "specialist physician", "symptoms", and "medication". Compared with severely disabled patients, those with no relevant disability at hospital discharge mentioned "symptoms" significantly more often. Regarding rehabilitation, "outpatient care" was mentioned more often by patients in an inpatient setting, and 11.8% without rehabilitation mentioned "depression". Patients in single-compared to multi-person households differed, for example, in the frequency of mentioning "specialist physicians" and gradually "outpatient care". A multivariate model yielded associations between the disability at discharge and the probability of mentioning relevant topics afterward. This study provided insights into the patients' perspective and identified topics that need attention while accompanying stroke and TIA patients after discharge. Further, the degree of disability at discharge might be helpful for planning individual aftercare.
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Transcatheter aortic valve replacement (TAVR) offers a novel treatment option for patients with severe symptomatic aortic valve stenosis, particularly for patients who are unsuitable candidates for surgical intervention. However, high therapeutical costs, socio-economic considerations, and numerous comorbidities make it necessary to target and allocate available resources efficiently. In the present study, we aimed to identify risk factors associated with futile treatment following transfemoral (TF) and transapical (TA) TAVR. Five hundred and thirty-two consecutive patients (82 ± 9 years, female 63%) who underwent TAVR between June 2009 and December 2016 at the Vienna Heart Center Hietzing were retrospectively analyzed to identify predictors of futility, defined as all-cause mortality at one year following the procedure for the overall patient cohort, as well as the TF and TA cohort. Out of 532 patients, 91 (17%) did not survive the first year after TAVR. A multivariate logistic model identified cerebrovascular disease, home oxygen dependency, wheelchair dependency, periinterventional myocardial infarction, and postinterventional renal replacement therapy as the factors independently associated with an increased one-year mortality. Our findings underscore the significance of a precise preinterventional evaluation, as well as illustrating the subtle differences in baseline characteristics in the TF and TA cohort and their impact on one-year mortality.
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INTRODUCTION: Post stroke management has moved into the focus as it represents the only way to secure acute treatment effects in the long term. Due to individual courses, post stroke management appears rather challenging and is hindered by existing barriers between treatment sectors. As a novel concept, the PostStroke-Manager combines digital and sensor-based technology with personal assistance to enable intersectoral cooperation, best possible reduction of stroke-related disability, optimal secondary prevention, and detection of physical and psychological comorbidities. METHODS: This prospective single-center observational study aims to investigate the feasibility of the PostStroke-Manager concept in an outpatient setting. Ninety patients who have suffered an ischemic or hemorrhagic stroke or transient ischemic attack will be equipped with a tablet and mobile devices recording physical activity, blood pressure, and electrocardiographic signals. Through a server-based platform, patients will be connected with the primary care physician, a stroke pilot and, if necessary, other specialists who will use web-based platforms. Via the tablet, patients will have access to an application with 10 newly designed components including, for instance, a communication tool, medication schedule, medical records platform, and psychometric screenings (e.g., depression, anxiety symptoms, quality of life, adherence, cognitive impairment). During the 1-year follow-up period, clinical visits are scheduled at three-month intervals. In the interim, communication will be secured by an appropriate tool that includes text messenger, audio, and video telephony. As the primary endpoint, feasibility will be measured by a 14-item questionnaire that addresses digital components, technical support, and personal assistance. The PostStroke-Manager will be judged feasible if at least 50% of these aspects are rated positively by at least 75% of patients. Secondary endpoints include feedback from professionals and longitudinal analyses on clinical and psychometric parameters. PERSPECTIVE: This study will answer the question of whether combined digital and personal support is a feasible approach to post stroke management. Furthermore, the patient perspective gained regarding digital support may help to specify future applications. This study will also provide information regarding the potential use of remote therapies and mobile devices in situations with limited face-to-face contacts. TRIAL REGISTRATION: German Register for Clinical Trials ( DRKS00023213 .), registered 27 April 2021.
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OBJECTIVES: Our goal was to develop a modified frozen elephant trunk (FET) prosthesis with a stented left subclavian artery (LSA) side branch for LSA connection and to perform preclinical testing in a human cadaver model. METHODS: We measured aortic diameters, distance between and diameters of supra-aortic vessels and the distance from the LSA offspring to the level of the left vertebral artery offspring in 70 patients. Based on these measurements, a novel FET prosthesis was developed (Cryolife/Jotec, Hechingen, Germany) featuring a stented side branch for an intrathoracic LSA connection. The feasibility and ease of implantation were tested in 2 human cadaver models at the Anatomical Institute of the Medical University Graz. A covered stent graft (Advanta V12™ by Atrium Medical Corp., Hudson, NH, USA) was used for an LSA extension. RESULTS: Accurate deployment of the novel FET prosthesis with anatomical orientation of the stented side branch towards the LSA ostium followed by consecutive stent graft deployment was feasible in both cases. Proximalizing the distal anastomosis level from zone 3 to zone 1 not only diminished the complexity of the procedure but substantially facilitated the completion of the distal anastomosis. A 2.5-cm long extension stent graft was sufficient to seal to the LSA and to maintain left vertebral artery patency in both cases. CONCLUSIONS: This initial study in human anatomical bodies could demonstrate the feasibility of implanting a newly designed FET prosthesis. This evolution of the FET technique has the potential to substantially ease total aortic arch replacement by proximalization of the distal anastomosis into zone 1 and by shortening spinal and lower body hypothermic circulatory arrest times via a stented side branch to the LSA. This direct connection enables early restoration of systemic perfusion.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular , Estudos de Viabilidade , Alemanha , Humanos , Stents , Artéria Subclávia/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of this study was to evaluate early- and mid-term outcome and aortic remodelling in patients undergoing implantation of 2 different frozen elephant trunk prostheses, either the Thoraflex™ hybrid (Vascutek, Inchinnan, UK) and the E-vita Open (Jotec Inc., Hechingen, Germany) for acute aortic dissection. METHODS: All consecutive patients [n = 88; median age 59 (49-67) years; 69% male] undergoing surgery with a frozen elephant trunk prosthesis for acute aortic dissection from August 2005 until March 2018 were included in this study. The Thoraflex™ device was implanted in 55 patients and the E-vita Open graft in 33 patients. RESULTS: Preoperative characteristics did not differ significantly between groups. There was also no statistically significant difference in postoperative outcome: in-hospital mortality (11% vs 12%; P > 0.99), stroke (18% vs 6%; P = 0.12) and spinal cord injury (6% vs 6%; P > 0.99). While there was no statistically significant difference in the occurrence of distal stent graft-induced new entries (16% vs 18%; P = 0.77), there was a significantly higher rate of secondary endovascular aortic interventions in the Thoraflex™ hybrid group (22% vs 0%; P = 0.003). There was a trend towards a higher rate of false lumen thrombosis at the level of the stent graft (74% vs 95%; P = 0.085) and was comparable at the thoraco-abdominal transition (53% vs 80%; P = 0.36) 1 year after implantation of the prostheses. CONCLUSIONS: In this comparison of 2 frozen elephant trunk prostheses, there is no evidence that different surgical techniques influence in-hospital outcome. At 1-year follow-up, patients who underwent implantation of the E-vita Open prosthesis showed a significantly reduced rate of secondary aortic interventions and a trend towards a higher rate of false lumen thrombosis which might be attributed to a longer coverage of the descending aorta due to a longer stent graft design and significantly more frequent implantation in zone 3.
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Aorta Torácica/cirurgia , Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Prótese Vascular , Idoso , Dissecção Aórtica/mortalidade , Aneurisma Aórtico/mortalidade , Implante de Prótese Vascular/mortalidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The electron transport chain in mitochondria of different organisms contains a mixture of common and specialised components. The specialised enzymes form branches to the universal electron path, especially at the level of ubiquinone, and allow the chain to adjust to different cellular and metabolic requirements. In plants, specialised components have been known for a long time. However, recently, the known number of plant respiratory chain dehydrogenases has increased, including both components specific to plants and those with mammalian counterparts. This review will highlight the novel branches and their consequences for the understanding of electron transport and redundancy of electron paths.
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Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Mitocôndrias/genética , Plantas/genética , Arabidopsis/enzimologia , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/fisiologia , Complexo II de Transporte de Elétrons/genética , Complexo II de Transporte de Elétrons/fisiologia , Glicerol-3-Fosfato Desidrogenase (NAD+)/genética , Glicerol-3-Fosfato Desidrogenase (NAD+)/fisiologia , Membranas Mitocondriais/fisiologia , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/fisiologia , NADH Desidrogenase/genética , NADH Desidrogenase/fisiologia , Especificidade por SubstratoRESUMO
The ion channel-forming peptide AlaM (alamethicin) is known to permeabilize isolated mitochondria as well as animal cells. When intact tobacco (Nicotiana tabacum L.) Bright Yellow-2 cells were treated with AlaM, the cells became permeable for low-molecular-mass molecules as shown by induced leakage of NAD(P)+. After the addition of cofactors and substrates, activities of cytosolic as well as mitochondrial respiratory enzymes could be directly determined inside the permeabilized cells. However, at an AlaM concentration at which the cytoplasmic enzymes were maximally accessible, the vacuole remained intact, as indicated by an unaffected tonoplast proton gradient. Low-flux permeabilization of plasma membranes and mitochondria at moderate AlaM concentrations was reversible and did not affect cell vigour. Higher AlaM concentrations induced cell death. After the addition of catalase that removes the H2O2 necessary for NADH oxidation by apoplastic peroxidases, mitochondrial oxygen consumption could be measured in permeabilized cells. Inhibitor-sensitive oxidation of the respiratory substrates succinate, malate and NADH was observed after the addition of the appropriate coenzymes (ATP, NAD+). The capacities of different pathways in the respiratory electron-transport chain could thus be determined directly. We conclude that AlaM permeabilization provides a very useful tool for monitoring metabolic pathways or individual enzymes in their native proteinaceous environment with controlled cofactor concentrations. Possible uses and limitations of this method for plant cell research are discussed.
Assuntos
Alameticina/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Ionóforos/farmacologia , Nicotiana/efeitos dos fármacos , Organelas/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Membranas Intracelulares/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ácidos Nicotínicos , Nucleotídeos , Consumo de Oxigênio , Permeabilidade , Nicotiana/metabolismo , Nicotiana/ultraestruturaRESUMO
BACKGROUND: The plant respiratory chain contains several energy-dissipating enzymes, these being type II NAD(P)H dehydrogenases and the alternative oxidase, not present in mammals. The physiological functions of type II NAD(P)H dehydrogenases are largely unclear and little is known about their responses to stress. In this investigation, potato plants (Solanum tuberosum L., cv. Desiree) were sprayed with antimycin A, an inhibitor of the cytochrome pathway. Enzyme capacities of NAD(P)H dehydrogenases (EC 1.6.5.3) and the alternative oxidase were then analysed in isolated leaf mitochondria. RESULTS: We report a specific decrease in internal rotenone-insensitive NADH dehydrogenase capacity in mitochondria from antimycin A-treated leaves. External NADPH dehydrogenase and alternative oxidase capacities remained unaffected by the treatment. Western blotting revealed no change in protein abundance for two characterised NAD(P)H dehydrogenase homologues, NDA1 and NDB1, nor for two subunits of complex I. The alternative oxidase was at most only slightly increased. Transcript levels of nda1, as well as an expressed sequence tag derived from a previously uninvestigated closely related potato homologue, remained unchanged by the treatment. As compared to the daily rhythm-regulated nda1, the novel homologue displayed steady transcript levels over the time investigated. CONCLUSIONS: The internal rotenone-insensitive NADH oxidation decreases after antimycin A treatment of potato leaves. However, the decrease is not due to changes in expression of known nda genes. One consequence of the lower NADH dehydrogenase capacity may be a stabilisation of the respiratory chain reduction level, should the overall capacity of the cytochrome and the alternative pathway be restricted.
Assuntos
Antimicina A/farmacologia , NADH Desidrogenase/metabolismo , Oxirredutases/metabolismo , Folhas de Planta/efeitos dos fármacos , Solanum tuberosum/efeitos dos fármacos , Western Blotting , Transporte de Elétrons/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Proteínas Mitocondriais , NAD/metabolismo , NADP/metabolismo , Oxirredução/efeitos dos fármacos , Folhas de Planta/enzimologia , Folhas de Planta/metabolismo , Proteínas de Plantas , Rotenona/farmacologia , Solanum tuberosum/enzimologia , Solanum tuberosum/metabolismo , Succinatos/metabolismoRESUMO
Plant cell wall polysaccharides are synthesised at the plasma membrane and in the Golgi apparatus. Current research efforts mainly try to address how these molecules are synthesised or modified. However, it is clear that polysaccharide synthesis in the two compartments needs to be carried out in a coordinated fashion, and that carbohydrates and proteins that are delivered from the Golgi to the cell surface have to undergo a range of modifications. Consequently, there appears to be a need for a fine-tuned system that coalesces signals from the wall, synthesis of carbohydrate-based molecules and vesicle shuttling. Several recent papers have scratched the surface for an initial understanding of these linked processes. For example, the impairment of the proton pumping activity in the trans-Golgi network, which is part of the cell's trafficking system, results in growth defects, changes in Golgi stack morphology and cellulose deficiency. An increased understanding of how cell wall synthesis is coordinated with the secretory machinery may facilitate avenues for modulating cell wall contents and therefore overall plant biomass.