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1.
Microbiol Resour Announc ; 12(12): e0052923, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37966239

RESUMO

We report here seven draft genomes of bacterial strains from two Danish wastewater facilities, two of which might be characterized as a new group within the Pseudomonas and Pseudochrobactrum genera, respectively. These genomes will provide useful references for understanding bacterial interactions and horizontal gene transfer within bacterial communities.

2.
Mol Reprod Dev ; 90(12): 810-823, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37671983

RESUMO

This study assessed the histones methylation profile (H3K4me3 and H3K9me3) in late preantral (PA) and early antral (EA) caprine follicles grown in vivo and in vitro, and the anethole effect during in vitro culture of PA follicles. Uncultured in vivo-grown follicles (PA, n = 64; EA, n = 73) were used as controls to assess the methylation profile and genes' expression related to apoptosis cascade (BAX, proapoptotic; BCL2, antiapoptotic), steroidogenesis (CYP17, CYP19A1), and demethylation (KDM1AX1, KDM1AX2, KDM3A). The isolated PA follicles (n = 174) were cultured in vitro for 6 days in α-MEM+ in either absence (control) or presence of anethole. After culture, EA follicles were evaluated for methylation, mRNA abundance, and morphometry. Follicle diameter increased after culture, regardless of treatment. The methylation profile and the mRNA abundance were similar between in vivo-grown PA and EA follicles. Anethole treatment led to higher H3K4me3 fluorescence intensity in EA follicles. The mRNA abundances of BAX, CYP17, and CYP19A1 were higher, and BCL2 and KDM3A were lower in in vitro-grown EA follicles than in vivo-grown follicles. In conclusion, in vitro follicle culture affected H3K4me3 fluorescence intensity, mRNA abundance of apoptotic genes, and steroidogenic and demethylase enzymes compared with in vivo-grown follicles.


Assuntos
Cabras , Lisina , Animais , Proteína X Associada a bcl-2/metabolismo , Cabras/metabolismo , Histonas , Esteroide 17-alfa-Hidroxilase/metabolismo , RNA Mensageiro/genética , Oócitos/metabolismo
3.
Sports Biomech ; : 1-20, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36223481

RESUMO

Several constraints, including environmental (e.g., aquatic resistance, temperature and viscosity), organismic (e.g., anthropometry, buoyancy) and task-related (e.g., imposed swim speed or stroke rate) impact motor coordination and swimming performance. As motor coordination requires structurally organising intra- and inter-limb coupling, the purpose of this review was to update the literature concerning coordination between the upper-limbs in front crawl swimming. We focused on the effects of biomechanical, physiological, and personal (gender, skill level, and age) factors on coordination and performance. In fact, it could be highlighted that upper-limbs coordination varies with organismic, task and environmental constraints, resulting in several available motor solutions that should be adopted according to how each swimmer deals with occurring constraints. As such, there is no ideal or optimal coordination pattern that youth, learners and less-skilled swimmers should imitate.

4.
Arch Biochem Biophys ; 730: 109419, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36183841

RESUMO

Exercise training provides several cardiovascular benefits in both physiological and pathological conditions; however, its use as a therapeutic tool for pulmonary arterial hypertension (PAH) has been poorly explored. This study aimed to extend the comprehension of the cardioprotective effects of exercise training in the set of PAH focusing on the metabolic changes promoted by exercise in the right ventricle (RV). The monocrotaline animal model of PAH was used and male Wistar rats were submitted to two weeks of treadmill exercise training (5 days/week, 60 min/day, 25 m/min) following disease establishment. Trained rats showed an improved diastolic function (lower end-diastolic pressure and tau) despite the presence of cardiac overload (increased peak systolic pressure, end-diastolic pressure and arterial elastance). This enhanced hemodynamic response was paralleled by an increased uptake of glucose to cardiomyocytes through glucose transporter type 4 (GLUT4) followed by increased lactate dehydrogenase (LDH) activity. Exercise did not reverse the decrease of fatty acid oxidation related to PAH but increased the content of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Two weeks of exercise did not modulate the changes in amino acid metabolism secondary to PAH. Our work suggests that continuous aerobic exercise of moderate intensity, despite its short-term duration and application in a late stage of the disease, supports the RV response to PAH by promoting a shift in the cardiac metabolic phenotype.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Masculino , Ratos , Animais , Monocrotalina/efeitos adversos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/patologia , PPAR gama/metabolismo , Transportador de Glucose Tipo 4 , Ratos Wistar , Modelos Animais de Doenças , Glucose , Lactato Desidrogenases/metabolismo , Aminoácidos , Ácidos Graxos
5.
Artigo em Inglês | MEDLINE | ID: mdl-35742277

RESUMO

This study investigated the effects of a coordinative in-water training. Total 26 young swimmers (16 boys) were divided in a training group (that performed two sets of 6 × 25-m front crawl, with manipulated speed and stroke frequency, two/week for eight weeks) and a control group. At the beginning and end of the training period, swimmers performed 50-m front crawl sprints recorded by seven land and six underwater Qualisys cameras. A linear mixed model regression was applied to investigate the training effects adjusted for sex. Differences between sex were registered in terms of speed, stroke length, and stroke index, highlighting that an adjustment for sex should be made in the subsequent analysis. Between moments, differences were noticed in coordinative variables (higher time spent in anti-phase and push, and lower out-of-phase and recovery for training group) and differences between sex were noticed in performance (stroke length and stroke index). Interactions (group * time) were found for the continuous relative phase, speed, stroke length, and stroke index. The sessions exerted a greater (indirect) influence on performance than on coordinative variables, thus, more sessions may be needed for a better understanding of coordinative changes since our swimmers, although not experts, are no longer in the early learning stages.


Assuntos
Modalidades de Fisioterapia , Natação , Fenômenos Biomecânicos , Humanos , Masculino
6.
Waste Manag ; 134: 110-119, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34418741

RESUMO

A membrane bioreactor inoculated with commercial baker's yeast (Saccharomyces cerevisiae) (MBRy) integrated to an air-stripping/absorption (AS/AB) as pre-treatment (aiming ammonia recovery) or a post-treatment (polishment step) was assessed for the landfill leachate treatment. The effect of chemical oxygen demand (COD) and nitrogen (N) ratio (C:N) on the performance of the MBRy was also investigated. At high COD/N ratio, high organic matter removal in terms of COD (71 ± 4%) and ammonia removal (97 ± 3%) was observed. Lower COD/N ratio favored yeast growth in the mixed liquor even under adverse conditions. The results of ammonia removal and recovery, and economic analysis demonstrated that the best way to integrate the AS/BS processes is as pre-treatment of MBRy. The ammonia concentration in the AS/AB process feed was a key factor to achieve the market specification. Although pH and temperature adjustment were adequate to promote ammonia removal/recovery, the AS operation at high temperatures showed the highest ammonia removal rate (99%). Therefore, the integration of AS/AB with MBRy allows obtaining a permeate with a final concentration of 2902 ± 374 mg L-1 of COD and 9 ± 7.5 mg L-1 of ammonia. Although it was possible to reach the Brazilian discharge standard for ammonia (20 mg L-1), it was not possible to reach the standard for COD, where the remaining fraction is recalcitrant organic matter, requiring the integration of a physico-chemical process. It should be noted that the proposed route allowed recovery 7 kg of ammonia per m3 of treated leachate.


Assuntos
Poluentes Químicos da Água , Amônia , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos , Análise Custo-Benefício , Nitrogênio , Poluentes Químicos da Água/análise
8.
Artigo em Inglês | MEDLINE | ID: mdl-33921424

RESUMO

This study aimed to investigate the relationship between health perception and health predictors among the elderly. In this study, 376 older adults from four different countries (Hungary, n = 86; Italy, n = 133; Portugal, n = 95; and Spain, n = 62) were analyzed. All subjects completed the EQ-5D-5L to assess their quality-adjusted life years and were assessed in handgrip (HG) and in Timed Up and Go (TUG) tests. A three-way MANOVA was conducted to analyze the groups based on their age, sex, and country. The interaction effects in all included variables were also considered. The Bonferroni test was also executed as a post hoc test. Any interaction results were noticed. Regarding age, lower perceived quality of life scores and higher TUG results were registered in the oldest group, and greater values of left and right HG results were registered in the second-oldest group. Males showed greater left and right HG values than women. Spain showed lower perceived quality of life scores. Portugal and Italy showed greater HG left values, while Portugal had better HG right values. Hungary produced the greatest TUG scores. Quality of life is dependent on the subject's age and physical fitness, as increasing age was associated with decreased values of HG and TUG. Only strength was different between sexes.


Assuntos
Força da Mão , Qualidade de Vida , Idoso , Europa (Continente) , Feminino , Humanos , Hungria , Itália , Masculino , Percepção , Portugal , Espanha
9.
Int J Sports Physiol Perform ; 15(5): 731-740, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32015214

RESUMO

PURPOSE: The purposes of this study were to (1) analyze the variations of acute and chronic training load and well-being measures during 3 periods of the season (early, mid, and end) and (2) test the associations between weekly training load and well-being measures during different periods of the season. METHODS: Thirteen professional volleyball players from a team competing in the Portuguese Volleyball First Division (age 31.0 [5.0] y) were monitored during an entire season. Weekly acute (wAL) and chronic load (wCL), acute to chronic workload ratio (wACWL), and training monotony (wTM) were calculated during all weeks of the season. The weekly values of muscle soreness (wDOMS), stress (wStress), fatigue (wFatigue), sleep (wSleep), and Hooper index (wHI) were also obtained across the season. RESULTS: The midseason had meaningfully low values of wAL (-26.9%; effect size [ES]: -1.12) and wCL (-28.0%; ES: -2.81), and greater values of wACWL (+38.9%; ES: 2.81) compared with early season. The wCL (+10.6%; ES: 0.99), wStress (44.6%; ES: 0.87), and wHI (29.0%; ES: 0.62) were meaningfully greater during the end of season than in midseason. Overall, wAL presented very large correlations with wDOMS (r = .80), wSleep (r = .72), and wFatigue (r = .82). CONCLUSIONS: The results of this study suggest that the load was meaningfully higher during early season; however, stress was higher during the final stages of the season. Overall, it was also found that the acute load is more highly correlated with well-being status and its variations than chronic load or training monotony.


Assuntos
Comportamento Competitivo/fisiologia , Nível de Saúde , Condicionamento Físico Humano/métodos , Estações do Ano , Voleibol/fisiologia , Voleibol/psicologia , Adulto , Humanos , Fadiga Mental/etiologia , Mialgia/etiologia , Percepção/fisiologia , Condicionamento Físico Humano/fisiologia , Esforço Físico/fisiologia , Sono , Estresse Psicológico/etiologia
10.
Motor Control ; 23(4): 535-552, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31010390

RESUMO

This study aimed to examine young swimmers' behavioral flexibility when facing different task constraints, such as swimming speed and stroke frequency. Eighteen (five boys and 13 girls) 13- to 15-year-old swimmers performed a 15 × 50-m front crawl with five trials, at 100%, 90%, and 70% each of their 50 m maximal swimming speed and randomly at 90%, 95%, 100%, 105%, and 110% of their preferred stroke frequency. Seven aerial and six underwater cameras were used to assess kinematics (one cycle), with upper-limb coordination computed through a continuous relative phase and index of coordination. A cluster analysis identified six patterns of coordination used by swimmers when facing various speed and stroke frequency constraints. The patterns' nature and the way the swimmers shifted between them are more important than getting the highest number of patterns (range of repertoire), that is, a change in the motor pattern in order to adapt correctly is more important than being able to execute a great number of patterns.

11.
Motor Control ; 23(3): 354-364, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30599800

RESUMO

To analyze young swimmers' performance regarding sex and skill level, 23 boys and 26 girls (15.7 ± 0.8 and 14.5 ± 0.8 years old, respectively) were assessed for anthropometry, flexibility, strength, drag, coordination, and biomechanical variables. During a 50-m maximal front-crawl bout, seven aerial and six underwater Qualisys cameras assessed kinematics, and a load cell was used to measure drag (Tedea, United Kingdom) and tethered swimming force. A multivariate analysis of variance test (p < .05) enabled us to observe differences between skill levels in speed, stroke frequency, stroke index, and intracyclic velocity variations, but most relevant differences were noticed when comparing sexes, particularly for anthropometrics, shoulder flexibility, speed, stroke frequency, stroke length, drag, mechanical power, power per stroke, and maximal and mean force. Considering the included variables, only male swimmers' performance could be predicted through multiple linear regression, with stroke index, left shoulder flexion, and intracycle velocity variations showing great importance in achieving better results.


Assuntos
Desempenho Atlético/fisiologia , Fenômenos Biomecânicos/fisiologia , Natação/fisiologia , Adolescente , Feminino , Humanos , Masculino
12.
J Pharm Sci ; 108(1): 439-450, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30165065

RESUMO

The present work presents an in-depth evaluation of continuously collected data during a twin-screw granulation and drying process performed on a continuous manufacturing line. During operation, the continuous line logs 49 univariate process variables, hence generating a large amount of data. Three identical 5-h continuous manufacturing runs were performed. Multivariate data analysis tools, more specifically latent variable modeling tools such as principal component analysis, were used to extract information from the generated data sets unveiling process trends and drifts. Furthermore, a statistical process monitoring strategy is presented. The approach is based on the application of multivariate statistical process monitoring to model the variables that remain around a steady state.


Assuntos
Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Dessecação/métodos , Análise Multivariada , Pós/química , Análise de Componente Principal
13.
Sci Total Environ ; 648: 44-55, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30110666

RESUMO

Achromobacter denitrificans strain PR1, previously found to harbour specific degradation pathways with high sulfamethoxazole (SMX) degradation rates, was bioaugmented into laboratory-scale membrane bioreactors (MBRs) operated under aerobic conditions to treat SMX-containing real domestic wastewater. Different hydraulic retention times (HRTs), which is related to reaction time and loading rates, were considered and found to affect the SMX removal efficiency. The availability of primary substrates was important in both bioaugmented and non-bioaugmented activated sludge (AS) for cometabolism of SMX. High HRT (24 h) resulted in low food to microorganism ratio (F/M) and low SMX removal, due to substrate limitation. Decrease in HRT from 24 h to 12 h, 6 h and finally 4 h led to gradual increases in primary substrates availability, e.g. organic compounds and ammonia, resulted in increased SMX removal efficiency and degradation rate, and is more favorable for high-rate wastewater treatment processes. After inoculation into the MBRs, the bioaugmentation strain was sustained in the reactor for a maximum of 31 days even though a significant decrease in abundance was observed. The bioaugmented MBRs showed enhanced SMX removal, especially under SMX shock loads compared to the control MBRs. The results of this study indicate that re-inoculation is required regularly after a period of time to maintain the removal efficiency of the target compound.


Assuntos
Achromobacter denitrificans/metabolismo , Reatores Biológicos/microbiologia , Sulfametoxazol/metabolismo , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Membranas Artificiais , Águas Residuárias/análise
14.
Biofouling ; 33(7): 556-566, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28675051

RESUMO

The impact of sludge retention time (SRT) on the biofouling of a membrane bioreactor (MBR) by extracellular polymeric substances (EPS) was investigated. The MBR was operated at 60 and 20 d SRT. The gel layer (recovered through optimized membrane autopsy methods) and the cake layer were analyzed for their content and profile of EPS proteins and polysaccharides. The change to a shorter SRT led to decreased membrane filterability, concomitant with a higher expression of EPS proteins in the cake layer, which were identified as being mainly related with biosynthesis and stress functions. The gel layer was more substantial in internal fibers, with polysaccharides being the major component in this layer. With the decrease in SRT (and filterability decrease), the overall polysaccharide content and sugar variety increased. In conclusion, SRT impacted not only on the quantity but also the composition of EPS molecules, and both were shown to be important in biofouling.


Assuntos
Incrustação Biológica , Reatores Biológicos/microbiologia , Membranas Artificiais , Esgotos/microbiologia , Purificação da Água/métodos , Filtração , Fatores de Tempo
15.
Int J Pharm ; 520(1-2): 29-38, 2017 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-28137428

RESUMO

Orthogonal partial least squares regression (OPLS) is being increasingly adopted as an alternative to partial least squares (PLS) regression due to the better generalization that can be achieved. Particularly in multivariate batch statistical process control (BSPC), the use of OPLS for estimating nominal trajectories is advantageous. In OPLS, the nominal process trajectories are expected to be captured in a single predictive principal component while uncorrelated variations are filtered out to orthogonal principal components. In theory, OPLS will yield a better estimation of the Hotelling's T2 statistic and corresponding control limits thus lowering the number of false positives and false negatives when assessing the process disturbances. Although OPLS advantages have been demonstrated in the context of regression, its use on BSPC was seldom reported. This study proposes an OPLS-based approach for BSPC of a cocrystallization process between hydrochlorothiazide and p-aminobenzoic acid monitored on-line with near infrared spectroscopy and compares the fault detection performance with the same approach based on PLS. A series of cocrystallization batches with imposed disturbances were used to test the ability to detect abnormal situations by OPLS and PLS-based BSPC methods. Results demonstrated that OPLS was generally superior in terms of sensibility and specificity in most situations. In some abnormal batches, it was found that the imposed disturbances were only detected with OPLS.


Assuntos
Cristalização/métodos , Análise dos Mínimos Quadrados , Controle de Qualidade , Ácido 4-Aminobenzoico/química , Hidroclorotiazida/química , Espectroscopia de Luz Próxima ao Infravermelho
16.
J Cardiovasc Pharmacol ; 69(3): 178-182, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28045761

RESUMO

INTRODUCTION: We examined the effects of the selective late INa inhibitor eleclazine on the 50% probability of successful defibrillation (DFT50) before and after administration of amiodarone to determine its suitability for use in patients with implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: In 20 anesthetized pigs, transvenous active-fixation cardiac defibrillation leads were fluoroscopically positioned into right ventricular apex through jugular vein. ICDs were implanted subcutaneously. Dominant frequency of ventricular fibrillation was analyzed by fast Fourier transform. The measurements were made before drug administration (control), and at 40 minutes after vehicle, eleclazine (2 mg/kg, i.v., bolus over 15 minutes), or subsequent/single amiodarone administration (10 mg/kg, i.v., bolus over 10 minutes). Eleclazine did not alter DFT50, dominant frequency, heart rate, or mean arterial pressure (MAP). Subsequent amiodarone increased DFT50 (P = 0.006), decreased dominant frequency (P = 0.022), and reduced heart rate (P = 0.031) with no change in MAP. Amiodarone alone increased DFT50 (P = 0.005; NS compared to following eleclazine) and decreased dominant frequency (P = 0.003; NS compared to following eleclazine). CONCLUSION: Selective late INa inhibition with eleclazine does not alter DFT50 or dominant frequency of ventricular fibrillation when administered alone or in combination with amiodarone. Accordingly, eleclazine would not be anticipated to affect the margin of defibrillation safety in patients with ICDs.


Assuntos
Amiodarona/uso terapêutico , Cardioversão Elétrica/métodos , Oxazepinas/uso terapêutico , Bloqueadores dos Canais de Sódio/uso terapêutico , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/fisiopatologia , Amiodarona/farmacologia , Animais , Masculino , Oxazepinas/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Suínos , Fibrilação Ventricular/terapia , Canais de Sódio Disparados por Voltagem/fisiologia
17.
Environ Sci Pollut Res Int ; 24(4): 3550-3561, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27878775

RESUMO

The treatment of large volumes of wastewater during oil refining is presently a challenge. Bioremediation has been considered an eco-friendly approach for the removal of polycyclic aromatic hydrocarbons (PAHs), which are one of the most hazardous groups of organic micropollutants. However, it is crucial to identify native PAH-removing microorganisms for the development of an effective bioremediation process. This study reports the high potential of an anaerobic microbial consortium enriched from a petrochemical refinery wastewater to remove two priority PAHs-acenaphthene and phenanthrene. Seventy-seven percent of acenaphthene was removed within 17 h, whereas phenanthrene was no longer detected after 15 h. Bioremoval rates were extremely high (0.086 and 0.156 h-1 for acenaphthene and phenanthrene, respectively). The characterization of the microbial communities by next-generation sequencing and fluorescence in situ hybridization showed that the PAH-removing consortium was mainly composed by bacteria affiliated to Diaphorobacter and Paracoccus genera, independently of the PAH tested. Moreover, besides biodegradation, biosorption was a relevant mechanism involved in the removal of both PAHs, which is an important finding since biosorption is less expensive than biodegradation and can be carried out with dead biomass. Although biodegradation is the most commonly reported biological mechanism for PAH removal, this study demonstrated that biosorption by this microbial community may be extremely efficient for their removal. Given the outstanding ability of this microbial consortium to quickly remove the compounds addressed, it could be further applied for the bioremediation of PAHs in refinery wastewaters and other contaminated environments.


Assuntos
Biodegradação Ambiental , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Bactérias/metabolismo , Biomassa , Hibridização in Situ Fluorescente , Consórcios Microbianos
18.
Appl Microbiol Biotechnol ; 100(19): 8507-21, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27270599

RESUMO

Membrane bioreactors (MBRs) are an advanced technology for wastewater treatment whose wide application has been hindered by rapid fouling of the membranes. MBRs can be operated with long sludge retention time (SRT), a crucial parameter impacting microbial selection in the reactor. This also affects filtration performance, since a major fouling agent are the extracellular polymeric substances (EPS). In this study, the impact of the SRT on the ecophysiology of the MBRs and, consequently, on membrane fouling was evaluated. A MBR was operated under a SRT of 60 days followed by a SRT of 20 days. A comprehensive analysis of the microbial community structure and EPS proteins and polysaccharide profiles of the mixed liquor and cake layer was carried out throughout both operation periods. The results of this study showed that the imposition of a shorter SRT led to a shift in the dominant bacterial populations. The mixed liquor and cake layer communities were very different, with Actinomycetales order standing out in the cake layer at SRT of 20 days. Overall, higher EPS concentrations (particularly proteins) were found at this SRT. Furthermore, EPS profiles were clearly affected by the SRT: it was possible to correlate a group of soluble EPS proteins with the SRT of 60 days, and a lower sludge age led to a lower diversity of polysaccharide sugar monomers, with an increase of glucose and galactose in the cake layer. This study improves our knowledge regarding the molecular reasons for fouling, which may contribute to improve MBR design and operation.


Assuntos
Proteínas de Bactérias/análise , Reatores Biológicos/microbiologia , Biota , Membranas/microbiologia , Polissacarídeos Bacterianos/análise , Fatores de Tempo , Águas Residuárias , Purificação da Água/métodos
19.
J Cardiovasc Electrophysiol ; 26(3): 329-35, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25346368

RESUMO

INTRODUCTION: Ventricular rate during atrial fibrillation (AF) can be reduced by slowing atrioventricular (AV) node conduction and/or by decreasing dominant frequency of AF. We investigated whether combined administration of ivabradine and ranolazine reduces ventricular rate during AF. METHODS AND RESULTS: Ivabradine (maximum clinical dose, 0.25 mg/kg, and 0.10 mg/kg, i.v.) and ranolazine (2.4 mg/kg, i.v., bolus followed by 0.135 mg/kg/min) were studied in an anesthetized pig (N = 16) model of AF. Combined administration of 0.25 mg/kg ivabradine with ranolazine reduced ventricular rate during AF by 51.9 ± 9.7 beats/min (23%, P = 0.017) and dominant frequency of AF by 2.8 ± 0.5 Hz (32%, P = 0.005). It increased PR (P = 0.0002, P = 0.0007) and A-H intervals (P = 0.047, P = 0.002) during pacing at 130 and 180 beats/min, respectively, to a greater degree than additive effects of single agents. Combined administration of 0.1 mg/kg ivabradine with ranolazine exceeded additive effects of single agents on A-H intervals and dominant frequency of AF. Moreover, ranolazine potentiated low-dose ivabradine's reduction in ventricular rate, as combined administration more than doubled effects of the higher ivabradine dose alone and was similar to the combination with the higher dose. Neither drug nor their combination affected contractility (left ventricular [LV] dP/dt), QT or His-ventricular (H-V) intervals, or mean arterial pressure during sinus rhythm or AF. CONCLUSION: Combined administration of ivabradine and ranolazine at clinically safe levels decreases ventricular rate during AF by reducing AV node conduction and AF dominant frequency without QT prolongation or depression in contractility. Targeting these actions offers intrinsic advantages over conventional nodal agents, which can reduce contractility.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Benzazepinas/administração & dosagem , Fármacos Cardiovasculares/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Ranolazina/administração & dosagem , Animais , Fibrilação Atrial/fisiopatologia , Quimioterapia Combinada , Cobaias , Frequência Cardíaca/fisiologia , Ivabradina , Masculino , Suínos
20.
Heart Rhythm ; 11(12): 2288-96, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25111327

RESUMO

BACKGROUND: If channels are functionally expressed in atrioventricular (AV) nodal tissue. OBJECTIVE: The purpose of this study was to address whether the prototypical If inhibitor, ivabradine, at clinically safe concentrations can slow AV node conduction to reduce ventricular rate (VR) during atrial fibrillation (AF). METHODS: Effects of ivabradine (0.1 mg/kg i.v. bolus) were studied in an anesthetized Yorkshire pig (N = 7) model of AF and in isolated guinea pig hearts (N = 7). RESULTS: Ivabradine reduced heart rate (P = .0001) without affecting mean arterial pressure during sinus rhythm. The agent lengthened PR intervals in a rate-dependent manner (P = .0009) by 14 ± 2.7 ms (P = .003) and 25 ± 3.0 ms (P = .0004) and increased atrial-His (A-H) intervals in a rate-dependent manner (P = .020) by 10 ± 1.7 ms and 17 ± 2.8 ms during pacing at 130 and 180 bpm, respectively (both P = .0008). Similar rate-dependent effects were observed in isolated guinea pig hearts. Ivabradine slowed VR during AF from 240 ± 21 bpm to 211 ± 25 bpm (P = .041). The ivabradine-induced increase in A-H interval was inversely correlated with VR (r = -0.85, P = .03, at 130 bpm; r = -0.95, P = .003, at 180 bpm). QT and HV intervals, AF dominant frequency (8.5 ± 0.9 to 8.7 ± 1.1 Hz, P = NS), mean arterial pressure, and left ventricular dP/dt (1672 ± 222 to 1889 ± 229 mm Hg/s, P = NS) during AF were unaffected. CONCLUSION: Ivabradine's rate-dependent increase in A-H interval is highly correlated with VR during AF. As dominant frequency was unaltered, AV node conduction slowing during high nodal activation rates appears to be the main mechanism of ivabradine's VR reduction. If inhibition in the AV node may provide a promising target to slow VR during AF without depression in contractility.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Nó Atrioventricular/efeitos dos fármacos , Benzazepinas/farmacologia , Eletrocardiografia , Função Ventricular Esquerda/efeitos dos fármacos , Análise de Variância , Animais , Fibrilação Atrial/fisiopatologia , Nó Atrioventricular/fisiopatologia , Benzazepinas/farmacocinética , Cateterismo Cardíaco , Fármacos Cardiovasculares/farmacologia , Modelos Animais de Doenças , Fluoroscopia/métodos , Cobaias , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Infusões Intravenosas , Ivabradina , Masculino , Pulsoterapia , Distribuição Aleatória , Valores de Referência , Sus scrofa , Suínos
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