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1.
Curr Treat Options Cardiovasc Med ; 21(9): 43, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31342171

RESUMO

PURPOSE OF REVIEW: Atrial fibrillation (AF) predisposes to embolic strokes and reduced quality of life. Ablation (catheter-based or surgically performed) can be employed to promote the maintenance of sinus rhythm in a carefully selected subset of patients with AF. The goal of this review is to discuss the indications and techniques for AF ablation, as well as post-procedural outcomes. RECENT FINDINGS: Atrial fibrillation ablation improves quality of life in patients with atrial fibrillation although no clear reduction in stroke or overall mortality has been shown. Familiarity with the indications for AF ablation is important for all cardiologists, as is having a sound understanding of the efficacy of the procedure and potential complications. Furthermore, acquiring a grasp of the different modalities of AF ablation (including percutaneous endocardial techniques and surgical ablation approaches) will help to facilitate effective and appropriate referrals.

2.
Curr Protoc Pharmacol ; 80(1): 11.21.1-11.21.17, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-30040212

RESUMO

Intracellular organelles are membranous structures central for maintaining cellular physiology and the overall health of the cell. To maintain cellular function, intracellular organelles are required to tightly regulate their ionic homeostasis. Any imbalance in ionic concentrations can disrupt energy production (mitochondria), protein degradation (lysosomes), DNA replication (nucleus), or cellular signaling (endoplasmic reticulum). Ionic homeostasis is also important for volume regulation of intracellular organelles and is maintained by cation and anion channels as well as transporters. One of the major classes of ion channels predominantly localized to intracellular membranes is chloride intracellular channel proteins (CLICs). They are non-canonical ion channels with six homologs in mammals, existing as either soluble or integral membrane protein forms, with dual functions as enzymes and channels. Provided in this overview is a brief introduction to CLICs, and a summary of recent information on their localization, biophysical properties, and physiological roles. © 2018 by John Wiley & Sons, Inc.


Assuntos
Canais de Cloreto/fisiologia , Animais , Agonistas dos Canais de Cloreto , Canais de Cloreto/antagonistas & inibidores , Humanos , Organelas
3.
Physiol Rep ; 6(12): e13748, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29932499

RESUMO

Large conductance calcium and voltage-activated potassium channels (BKCa ) are transmembrane proteins, ubiquitously expressed in the majority of organs, and play an active role in regulating cellular physiology. In the heart, BKCa channels are known to play a role in regulating the heart rate and protect it from ischemia-reperfusion injury. In vascular smooth muscle cells, the opening of BKCa channels results in membrane hyperpolarization which eventually results in vasodilation mediated by a reduction in Ca2+ influx due to the closure of voltage-dependent Ca2+ channels. Ex vivo studies have shown that BKCa channels play an active role in the regulation of the function of the majority of blood vessels. However, in vivo role of BKCa channels in cardiovascular function is not completely deciphered. Here, we have evaluated the rapid in vivo role of BKCa channels in regulating the cardiovascular function by using two well-established, rapid-acting, potent blockers, paxilline and iberiotoxin. Our results show that BKCa channels are actively involved in regulating the heart rate, the function of the left and right heart as well as major vessels. We also found that the effect on BKCa channels by blockers is completely reversible, and hence, BKCa channels can be exploited as potential targets for clinical applications for modulating heart rate and cardiac contractility.


Assuntos
Frequência Cardíaca/fisiologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/fisiologia , Função Ventricular/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Coronária/efeitos dos fármacos , Circulação Coronária/fisiologia , Ecocardiografia , Coração/diagnóstico por imagem , Frequência Cardíaca/efeitos dos fármacos , Indóis/farmacologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/antagonistas & inibidores , Masculino , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiologia , Ratos Sprague-Dawley , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular/efeitos dos fármacos
4.
Am J Cardiol ; 119(9): 1387-1391, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28258728

RESUMO

Obstructive sleep apnea (OSA) and single nucleotide polymorphisms (SNPs) at the 4q25 locus are associated with increased risk of atrial fibrillation (AF). Whether these associations are independent of traditional risk factors for AF remains unknown. Using billing code queries and manual chart review, we assembled a cohort of adults that underwent overnight polysomnography and at least 1 12-lead electrocardiogram. Case status was defined by electrocardiographic data in support of AF or documentation of AF by a staff cardiologist. Controls were defined by a lack of primary evidence of AF and absence of a diagnosis of AF in the medical record. OSA severity was categorized based on Apnea-Hypopnea Index. Genotyping for a key 4q25 SNP (rs2200733) was performed using the Sequenom platform. Logistic regression was used to test for associations of AF with OSA category and 4q25 SNP genotype while adjusting for age, gender, body mass index, ancestry, hypertension status, and heart failure status. The cohort consisted of 674 subjects (62 ± 13 years; 44% women), including 132 patients with AF. After adjustment for established risk factors, the association between AF and OSA severity was borderline significant (odds ratio 1.2, 95% CI 1.0 to 1.5). The association between AF and 4q25 SNP status remained significant in a fully adjusted model that included OSA severity (odds ratio 1.5, 95% CI 1.3 to 5.7). In conclusion, OSA severity and the chromosome 4q25 SNP genotype were associated with AF status independent of clinical risk factors. Knowledge of AF-related SNPs may enhance AF risk stratification for those undergoing polysomnography.


Assuntos
Fibrilação Atrial/genética , Cromossomos Humanos Par 4/genética , Apneia Obstrutiva do Sono/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Polissonografia , Fatores de Risco , Índice de Gravidade de Doença
5.
JACC Clin Electrophysiol ; 3(12): 1356-1365, 2017 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-29759664

RESUMO

OBJECTIVES: This study sought to assess long-term left atrial appendage (LAA) closure efficacy of the Atriclip applied via totally thoracoscopic (TT) approach with computed tomographic angiography. BACKGROUND: LAA closure is associated with a low risk for atrial fibrillation-related embolic stroke. The Atriclip exclusion device allows epicardial LAA closure, avoiding the need for post-operative oral anticoagulation. Previous data with Atriclip during open chest procedures show a high efficacy rate of closure >95%. METHODS: Three-dimensional volumetric 2-phase computed tomographic angiography ≥90 days post-implantation was independently assessed by chest radiology for complete LAA closure on all consented subjects identified retrospectively as having had a TT-placed Atriclip at Vanderbilt University Medical Center from June 13, 2011, to October 6, 2015. RESULTS: Complete LAA closure (defined by complete exclusion of the LAA with no exposed trabeculations, and clip within 1 cm from the left circumflex artery) was found in 61 of 65 subjects (93.9%). Four cases had incomplete closure (6.2%). Two clips were placed too distally, leaving a large stump with exposed trabeculae. Two clips failed to address a secondary LAA lobe. No major complications were associated with TT placement of the Atriclip. Follow-up over 183 patient-years revealed 1 stroke in a patient with complete LAA closure and no thrombus (hypertensive cerebrovascular accident). CONCLUSIONS: Angiographic LAA closure efficacy with a TT-placed Atriclip is high (93.9%). The clinical significance of a remnant stump is unknown. Confirmation of complete LAA occlusion should be made before cessation of systemic anticoagulation.


Assuntos
Apêndice Atrial/cirurgia , Embolia Intracraniana/patologia , Toracoscopia/métodos , Idoso , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/complicações , Procedimentos Cirúrgicos Cardíacos/métodos , Angiografia por Tomografia Computadorizada/métodos , Ecocardiografia Transesofagiana , Feminino , Humanos , Embolia Intracraniana/etiologia , Embolia Intracraniana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Instrumentos Cirúrgicos , Oclusão Terapêutica/instrumentação , Trombose/etiologia , Resultado do Tratamento , Técnicas de Fechamento de Ferimentos/instrumentação
6.
J Cardiovasc Electrophysiol ; 26(10): 1111-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26222980

RESUMO

INTRODUCTION: Cardiac implantable electronic device (CIED) infections are potentially preventable complications associated with high morbidity, mortality, and cost. A recently developed bio-absorbable antibacterial envelope (TYRX™-A) might prevent CIED infections in high-risk subjects. However, data regarding safety and efficacy have not been published. METHODS AND RESULTS: In a single-center retrospective cohort study, we compared the prevalence of CIED infections among subjects with ≥2 risk factors treated with the TYRX™-A envelope (N = 135), the nonabsorbable TYRX™ envelope (N = 353), and controls who did not receive an envelope (N = 636). Infection was ascertained by individual chart review. The mean (95% confidence interval) number of risk factors was 3.08 (2.84-3.32) for TYRX™-A, 3.20 (3.07-3.34) for TYRX™, and 3.09 (2.99-3.20) for controls, P = 0.3. After a minimum 300 days follow-up, the prevalence of CIED infection was 0 (0%) for TYRX™-A, 1 (0.3%) for TYRX™, and 20 (3.1%) for controls (P = 1 for TYRX™-A vs. TYRX™, P = 0.03 for TYRX™-A vs. controls, and P = 0.002 for TYRX™ vs. controls). In a propensity score-matched cohort of 316 recipients of either envelope and 316 controls, the prevalence of infection was 0 (0%) and 9 (2.8%), respectively, P = 0.004. When limited to 122 TYRX™-A recipients and 122 propensity-matched controls, the prevalence of CIED infections was 0 (0%) and 5 (4.1%), respectively, P = 0.024. CONCLUSIONS: Among high-risk subjects, the TYRX™-A bio-absorbable envelope was associated with a very low prevalence of CIED related infections that was comparable to that seen with the nonabsorbable envelope.


Assuntos
Antibacterianos/administração & dosagem , Desfibriladores Implantáveis/estatística & dados numéricos , Implantes de Medicamento/administração & dosagem , Marca-Passo Artificial/estatística & dados numéricos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/prevenção & controle , Implantes Absorvíveis/estatística & dados numéricos , Idoso , Causalidade , Estudos de Coortes , Preparações de Ação Retardada/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Infecções Relacionadas à Prótese/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida , Tennessee/epidemiologia , Resultado do Tratamento
8.
Sci Pharm ; 79(1): 113-22, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21617776

RESUMO

A simple, specific and stability indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of paracetamol and lornoxicam in tablet dosage form. A Brownlee C-18, 5 µm column having 250×4.6 mm i.d. in isocratic mode, with mobile phase containing 0.05 M potassium dihydrogen phosphate:methanol (40:60, v/v) was used. The flow rate was 1.0 ml/min and effluents were monitored at 266 nm. The retention times of paracetamol and lornoxicam were 2.7 min and 5.1 min, respectively. The linearity for paracetamol and lornoxicam were in the range of 5-200 µg/ml and 0.08-20 µg/ml, respectively. Paracetamol and lornoxicam stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation and dry heat degradation. The proposed method was validated and successfully applied to the estimation of paracetamol and lornoxicam in combined tablet dosage form.

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