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1.
Dtsch Med Wochenschr ; 144(18): 1280-1285, 2019 09.
Artigo em Alemão | MEDLINE | ID: mdl-31514219

RESUMO

Supraventricular tachyarrhythmias, especially atrial fibrillation, are common in cardiac and non-cardiac patients with or without surgery. Prolonged rhythm disturbances may impair cardiac function and worsen the clinical outcome and prognosis. Therefore, heart rate control may be necessary to prevent cardiovascular events.Esmolol and landiolol as ultrashort and rapid acting highly selective ß 1 -adrenergic blockers are of particular interest in the prevention and management of cardiac arrhythmias. This review gives an update on both betablockers and their role in the management of arrhythmias in emergency medicine and perioperative setting.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Estado Terminal/terapia , Morfolinas/uso terapêutico , Propanolaminas/uso terapêutico , Ureia/análogos & derivados , Fibrilação Atrial/tratamento farmacológico , Humanos , Ureia/uso terapêutico
2.
Zhonghua Yi Xue Za Zhi ; 99(17): 1317-1322, 2019 May 07.
Artigo em Chinês | MEDLINE | ID: mdl-31091579

RESUMO

Objective: To investigate the effect of esmolol in septic shock patients with tachycardia. Methods: A prospective randomized controlled trial was conducted. Screening septic shock patients that admitted to Department of General Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from June 2016 to August 2017. After 24 h resuscitation therapy, 100 cases of septic shock patients with tachycardia (heart rate>100 bpm) were divided into esmolol group (n=50) and control group (n=50) with random number table. Patients in esmolol group accepted standard treatment plus esmolol injection with an initial dose of 25 mg/h. Heart rate target is 80 to 100 bpm. Patients in esmolol group continued to use esmolol for 7 days or to the day the patient left the ICU when the heart rate didn't achieve the target. Patients in control group were given standard treatment. Primary outcome was 28 d mortality. Secondary outcomes included heart rate, norepinephrine dosages, lactate level, inflammatory markers in per day during the trial; acute physiology and chronic health evaluation (APACHE Ⅱ) and sequential organ failure assessment (SOFA) on day 1, 3, 5, 7; length of hospital stay, length of mechanical ventilation, medication time of vasoactive agent. The data were compared with t test or rank sum test between the two groups. Results: The 28 d mortality of esmolol group and control group was 62%, 68%, respectively(χ(2)=0.529, P=0.529). Logistic regression analysis showed that primary heart rate (increase of 10 bpm, OR=1.568, 95%CI: 1.039-1.238, P=0.027), primary APACHEⅡ (OR=1.134, 95%CI: 1.026-1.239, P=0.005), integral heart rate (per 10 bpm, OR=2.207, 95%CI: 1.400-3.479, P=0.001) were independent risk factors for 28 d mortality. Compared with control group, the esmolol group had a lower heart rate on day 1-7; but over all, there was no statistically significant difference in heart rate between the two groups (P>0.05). There was no significant difference in total does of norepinephrine, lactate level, inflammatory markers, APACHE Ⅱ, SOFA, length of hospital stay between the two groups (all P>0.05). Conclusion: Tachycardia significantly increases the risk of death in patients with septic shock, esmolol may decrease the mortality by controlling heart rate.


Assuntos
Propanolaminas/uso terapêutico , Choque Séptico , Humanos , Estudos Prospectivos , Choque Séptico/tratamento farmacológico , Taquicardia
3.
BMJ Case Rep ; 12(3)2019 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-30852502

RESUMO

Current advanced cardiac life support (ACLS) guidelines for the management of ventricular fibrillation (VF) and pulseless ventricular tachycardia is defibrillation. However, refractory VF, which is defined as VF that persists despite three defibrillation attempts, is challenging for all ACLS providers; the best resuscitation strategy for patients that persist in refractory VF remains unclear. We report on a 51-year-old man who presented to the emergency department with chest pain and subsequently went into witnessed VF cardiac arrest. Despite standard ACLS management consisting of high-quality cardiopulmonary resuscitation, serial epinephrine and serial defibrillation, the return of spontaneous circulation (ROSC) was unable to be achieved. Double sequential defibrillation (DSD) was attempted multiple times unsuccessfully. After administration of low-dose esmolol, he immediately achieved ROSC. DSD and ß-blockade are increasingly recognised in the literature and practice for refractory VF. However, to the best of our knowledge, this is the first case of refractory VF that responded to low-dose esmolol ß-blockade.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Propanolaminas/uso terapêutico , Fibrilação Ventricular/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
4.
J Emerg Med ; 56(3): 308-318, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30711368

RESUMO

BACKGROUND: Recent-onset atrial fibrillation (RAF) is the most frequent supraventricular dysrhythmia in emergency medicine. Severely compromised patients require acute treatment with injectable drugs OBJECTIVE: The main purpose of this external validity study was to compare the short-term efficacy of esmolol with that of amiodarone to treat severe RAF in an emergency setting. METHODS: This retrospective survey was conducted in mobile intensive care units by analyzing patient records between 2002 and 2013. We included RAF with (one or more) severity factors including: clinical shock, angina pectoris, ST shift, and very rapid ventricular rate. A blind matching procedure was used to constitute esmolol group (n = 100) and amiodarone group (n = 200), with similar profiles for age, gender, initial blood pressure, heart rate, severity factors, and treatment delay. The main outcome measure was the percentage of patients with a ventricular rate control defined as heart frequency ≤ 100 beats/min. More stringent (rhythm control) and more humble indicators (20% heart rate reduction) were analyzed at from 10 to 120 min after treatment initiation. RESULTS: Patient characteristics were comparable for both groups: age 66 ± 16 years, male 71%, treatment delay < 1 h 36%, 1-2 h 29%, > 2 h 35%, chest pain 61%, ST shift 62%, ventricular rate 154 ± 26 beats/min, and blood pressure 126/73 mm Hg. The superiority of esmolol was significant at 40 min (64% rate control with esmolol vs. 25% with amiodarone) and for all indicators from 10 to 120 min after treatment onset. CONCLUSION: In "real life emergency medicine," esmolol is better than amiodarone in the treatment of RAF.


Assuntos
Amiodarona/normas , Fibrilação Atrial/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Propanolaminas/normas , Antagonistas de Receptores Adrenérgicos beta 1/normas , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Amiodarona/uso terapêutico , Antiarrítmicos/normas , Antiarrítmicos/uso terapêutico , Medicina de Emergência/métodos , Medicina de Emergência/normas , Serviço Hospitalar de Emergência/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propanolaminas/uso terapêutico , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de Tempo
6.
Perfusion ; 34(1): 67-75, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30058944

RESUMO

INTRODUCTION: This experimental study compares myocardial function after prolonged arrest by St. Thomas' Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas' Hospital No 2, both administered as cold oxygenated blood cardioplegia. METHODS: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples. RESULTS: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both). CONCLUSION: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB.


Assuntos
Soluções Cardioplégicas/uso terapêutico , Ponte Cardiopulmonar/métodos , Parada Cardíaca Induzida/métodos , Disfunção Ventricular Esquerda/etiologia , Adenosina/efeitos adversos , Adenosina/uso terapêutico , Animais , Soluções Cardioplégicas/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Modelos Animais de Doenças , Parada Cardíaca Induzida/efeitos adversos , Magnésio/efeitos adversos , Magnésio/uso terapêutico , Potássio/efeitos adversos , Potássio/uso terapêutico , Propanolaminas/efeitos adversos , Propanolaminas/uso terapêutico , Suínos , Disfunção Ventricular Esquerda/fisiopatologia
7.
Respir Physiol Neurobiol ; 259: 104-110, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30171906

RESUMO

While alveolar liquid clearance (ALC) mediated by the ß2-adrenergic receptor (ß2-AR) plays an important role in lung edema resolution in certain models of lung injury, in more severe lung injury models, this response might disappear. Indeed, we have shown that in an ischemia-reperfusion-induced lung injury model, ß2-agonists do not enhance ALC. The objective of this study was to determine if downregulation of the ß2-AR could explain the lack of response to ß2-agonists in this lung injury model. In an in vivo canine model of lung transplantation, we observed no change in ß2-AR concentration or affinity in the injured transplanted lungs compared to the native lungs. Furthermore, we could not enhance ALC in transplanted lungs with dcAMP + aminophylline, a treatment that bypasses the ß2-adrenergic receptor and is known to stimulate ALC in normal lungs. However, transplantation decreased αENaC expression in the lungs by 50%. We conclude that the lack of response to ß2-agonists in ischemia-reperfusion-induced lung injury is not associated with significant downregulation of the ß2-adrenergic receptors but is attributable to decreased expression of the ENaC channel, which is essential for sodium transport and alveolar liquid clearance in the lung.


Assuntos
Lesão Pulmonar , Alvéolos Pulmonares/fisiopatologia , Receptores Adrenérgicos beta 2/uso terapêutico , Traumatismo por Reperfusão/complicações , Aminofilina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Broncodilatadores/farmacologia , AMP Cíclico/farmacologia , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Canais Epiteliais de Sódio/metabolismo , Feminino , Frequência Cardíaca/efeitos dos fármacos , Imidazóis/uso terapêutico , Radioisótopos do Iodo/farmacocinética , Iodocianopindolol/farmacocinética , Lesão Pulmonar/etiologia , Lesão Pulmonar/fisiopatologia , Masculino , Propanolaminas/uso terapêutico , Ligação Proteica/efeitos dos fármacos , Edema Pulmonar/etiologia , RNA Mensageiro
8.
Exp Eye Res ; 180: 8-17, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30500363

RESUMO

Receptor interacting protein kinase 1 (RIPK1) plays a key role in necroptosis, which is a type of programmed necrosis that is involved in ocular diseases, including glaucoma and dry age-related macular degeneration (AMD). We previously introduced RIPK1-inhibitory compound (RIC), which has biochemical characteristics and a mode of action that are distinct from those of the prototype RIPK1 inhibitor necrostatin-1. The intraperitoneal administration of RIC exerts a protective effect on retinal ganglion cells against a glaucomatous insult. In this study, we examined the protective effect of RIC on retinal pigment epithelium (RPE) against sodium iodate (SI) insult, which is associated with dry AMD pathogenesis. The eye drop administration of RIC that reached on the retina prevented RPE loss in SI-induced retinal degeneration. RIC consistently demonstrated retinal protection in the funduscopy and electroretinogram analyses in SI-injected rabbits and iodoacetic acid-treated mini-pigs. Moreover, the in vivo protective effects of RIC were superior to those of ACU-4429 and doxycycline, which are other medications investigated in clinical trials for the treatment of dry AMD, and RIC did not induce retinal toxicity following topical administration in rats. Collectively, RIC displayed excellent retinal penetration and prevented retinal degeneration in the pathogenesis of dry AMD with a high in vivo efficacy.


Assuntos
Modelos Animais de Doenças , Atrofia Geográfica/prevenção & controle , Substâncias Protetoras/uso terapêutico , Proteína Serina-Treonina Quinases de Interação com Receptores/uso terapêutico , Células Ganglionares da Retina/efeitos dos fármacos , Administração Oftálmica , Animais , Eletrorretinografia , Atrofia Geográfica/induzido quimicamente , Atrofia Geográfica/patologia , Iodatos/toxicidade , Masculino , Oftalmoscopia , Éteres Fenílicos/uso terapêutico , Propanolaminas/uso terapêutico , Coelhos , Ratos , Ratos Sprague-Dawley , Degeneração Retiniana/prevenção & controle
9.
Oncol Rep ; 41(1): 341-350, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30542705

RESUMO

The ß2­adrenergic receptor (ß2­AR, encoded by the ADRB2 gene) is a member of the G­protein­coupled receptor superfamily that can be stimulated by catecholamines. Studies in vivo and in vitro have confirmed that ß­blockers (ß­AR antagonists) exert antitumor effects on various tumors. Furthermore, ADRB2 single­nucleotide polymorphisms (SNPs) have been identified to alter the expression and conformation of ß2­AR, which may alter the ß­blocker drug response. The aim of the present study was to investigate the effect of ß­blockers on triple­negative breast cancer cells and determine whether ADRB2 SNPs affect the response to ß­blocker drugs. Propranolol and ICI 118,551 significantly inhibited the viability of MDA­MB­231 cells, arrested cell cycle progression at G0/G1 and S phase and induced cell apoptosis. Western blot analysis indicated that the phosphorylation levels of extracellular­signal­regulated kinase (ERK)1/2 and the expression levels of cyclo­oxygenase 2 (COX­2) were significantly decreased following ß­blocker treatment. Four haplotypes, which comprised ADRB2 SNPs rs1042713 and rs1042714, were transfected into 293 cells. After 24 and 48 h of transfection, ADRB2 mRNA expression was significantly decreased in mutant groups compared with the wild­type group. The ADRB2 SNPs exerted no effect on cell viability, but did affect the drug response of ICI 118,551. Furthermore, ADRB2 SNPs also affected the regulatory function of ICI 118,551 on the ERK/COX­2 signaling pathway. Collectively, propranolol and ICI 118,551 inhibited the viability of MDA­MB­231 cells by downregulating the ERK/COX­2 signaling pathway and inducing apoptosis. The results of the present study indicated that SNPs rs1042713 and rs1042714 of ADRB2 affected the response to ICI 118,551, and the underlying molecular mechanism was elucidated.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Receptores Adrenérgicos beta 2/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Fosforilação/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Propranolol/farmacologia , Propranolol/uso terapêutico , Receptores Adrenérgicos beta 2/metabolismo , Neoplasias de Mama Triplo Negativas/genética
10.
Crit Care ; 22(1): 325, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30486866

RESUMO

BACKGROUND: Maximal left ventricular (LV) pressure rise (LV dP/dtmax), a classical marker of LV systolic function, requires LV catheterization, thus surrogate arterial pressure waveform measures have been proposed. We compared LV and arterial (femoral and radial) dP/dtmax to the slope of the LV end-systolic pressure-volume relationship (Ees), a load-independent measure of LV contractility, to determine the interactions between dP/dtmax and Ees as loading and LV contractility varied. METHODS: We measured LV pressure-volume data using a conductance catheter and femoral and radial arterial pressures using a fluid-filled catheter in 10 anesthetized pigs. Ees was calculated as the slope of the end-systolic pressure-volume relationship during a transient inferior vena cava occlusion. Afterload was assessed by the effective arterial elastance. The experimental protocol consisted of sequentially changing afterload (phenylephrine/nitroprusside), preload (bleeding/fluid bolus), and contractility (esmolol/dobutamine). A linear-mixed analysis was used to assess the contribution of cardiac (Ees, end-diastolic volume, effective arterial elastance, heart rate, preload-dependency) and arterial factors (total vascular resistance and arterial compliance) to LV and arterial dP/dtmax. RESULTS: Both LV and arterial dP/dtmax allowed the tracking of Ees changes, especially during afterload and contractility changes, although arterial dP/dtmax was lower compared to LV dP/dtmax (bias 732 ± 539 mmHg⋅s- 1 for femoral dP/dtmax, and 625 ± 501 mmHg⋅s- 1 for radial dP/dtmax). Changes in cardiac contractility (Ees) were the main determinant of LV and arterial dP/dtmax changes. CONCLUSION: Although arterial dP/dtmax is a complex function of central and peripheral arterial factors, radial and particularly femoral dP/dtmax allowed reasonably good tracking of LV contractility changes as loading and inotropic conditions varied.


Assuntos
Função Ventricular Esquerda/fisiologia , Pesos e Medidas/normas , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Animais , Cardiotônicos/uso terapêutico , Cateterismo Venoso Central/métodos , Contração Miocárdica/fisiologia , Nitroprussiato/uso terapêutico , Fenilefrina/uso terapêutico , Propanolaminas/uso terapêutico , Suínos , Vasodilatadores/uso terapêutico
11.
Medicine (Baltimore) ; 97(41): e12647, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30313053

RESUMO

INTRODUCTION: Intraoperative systemic esmolol has been shown to reduce postsurgical pain. Nonetheless, it is unknown whether the use of intraoperative systemic esmolol can improve patient-reported postsurgical quality of recovery. The main objective of the current investigation was to evaluate the effect of intraoperative esmolol on postsurgical quality of recovery. We hypothesized that patients receiving intraoperative esmolol would report better quality of postsurgical recovery than the ones receiving saline. METHODS: The study was a prospective randomized double-blinded, placebo-controlled, clinical trial. Healthy female subjects undergoing outpatient hysteroscopic surgery under general anesthesia were randomized to receive intravenous esmolol administered at a rate of 0.5 mg/kg bolus followed by an infusion of 5 to 15 µg/kg/min or the same volume of saline. The primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 hours after surgery. Other data collected included postoperative opioid consumption and pain scores. Data were analyzed using group t tests and the Wilcoxon exact test. RESULTS: Seventy subjects were randomized and 58 completed the study. There was not a clinically significant difference in the global QoR-40 scores between the esmolol and saline groups at 24 hours, median (interquartile range) of 179 (171-190) and 182 (173-189), respectively, P = .82. In addition, immediate post-surgical data in the post-anesthesia care unit did not show a benefit of using esmolol compared to saline in regard to pain scores, morphine consumption, and postoperative nausea and vomiting. CONCLUSIONS: Despite current evidence in the literature that intraoperative esmolol improves postsurgical pain, we did not detect a beneficial effect of intraoperative esmolol on patient-reported quality of recovery after ambulatory surgery. Our results confirm the concept that the use of patient-centered outcomes rather than commonly used outcomes (e.g., pain scores and opioid consumption) can change the practice of perioperative medicine.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Histeroscopia/métodos , Propanolaminas/uso terapêutico , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Analgésicos Opioides/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Histeroscopia/efeitos adversos , Percepção da Dor , Dor Pós-Operatória/epidemiologia , Náusea e Vômito Pós-Operatórios/epidemiologia , Propanolaminas/administração & dosagem , Estudos Prospectivos
12.
Int Heart J ; 59(5): 1169-1173, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30101848

RESUMO

It is widely known that ß-blockers exert beneficial effects on non-ischemic and ischemic systolic heart failure (sHF) in nonstructural hearts. However, whether ß-blockers exert similar effects on sHF associated with congenital heart disease (CHD), particularly in an anatomical right ventricle, remains under debate.Here we report the case of an adult man with repaired tetralogy of Fallot suffering from biventricular heart failure. Treatment with carvedilol directly improved the systolic function of the right and left ventricles. This case report strongly suggests there is potential for carvedilol to exert a beneficial effect on heart failure in CHD. The appropriate titration of carvedilol and patient follow-up for long-term effects are important when treating adult patients with CHD with ß-blockers.


Assuntos
Carbazóis/uso terapêutico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Propanolaminas/uso terapêutico , Sístole/efeitos dos fármacos , Tetralogia de Fallot/cirurgia , Função Ventricular Direita/efeitos dos fármacos , Antagonistas Adrenérgicos beta/uso terapêutico , Carbazóis/administração & dosagem , Carvedilol , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Propanolaminas/administração & dosagem , Resultado do Tratamento
13.
J Vet Emerg Crit Care (San Antonio) ; 28(5): 447-456, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30074662

RESUMO

OBJECTIVE: To determine the effects of esmolol on hemodynamics and heart rate variability (HRV) in the early stage of sepsis. DESIGN: Prospective, randomized, controlled, parallel trial. SETTINGS: Veterinary research laboratory. ANIMALS: Ten anesthetized piglets. INTERVENTIONS: Septic shock was induced by infusing a suspension of live Pseudomonas aeruginosa IV in 10 anesthetized piglets. The piglets were resuscitated according to a standardized protocol using Ringer's lactate solution, norepinephrine, and milrinone. Once stabilized, the piglets were randomized to receive IV esmolol, titrated to a heart rate <90/min, or control, receiving saline. A pulmonary artery catheter and an arterial catheter were inserted for hemodynamic measurements. The Analgesia/Nociception Index (ANI) and the normalized HRV frequency domain parameters - high-frequency (HF), low frequency (LF), LF/HF ratio - were recorded using a proprietary monitor. MEASUREMENTS AND MAIN RESULTS: A significant decrease in cardiac output and heart rate, and a significant increase in systemic vascular resistance were observed over time in the esmolol group in comparison to the control group. No other differences were observed in hemodynamic parameters. No significant differences were observed in ANI variations or HRV parameters over time between groups. CONCLUSIONS: The administration of esmolol produced significant changes in hemodynamics with no change in ANI values or HRV parameters. Further study is needed to understand the effect of esmolol during sepsis.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Propanolaminas/uso terapêutico , Infecções por Pseudomonas/veterinária , Choque Séptico/veterinária , Doenças dos Suínos/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Animais Recém-Nascidos , Débito Cardíaco/efeitos dos fármacos , Reanimação Cardiopulmonar/veterinária , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Monitorização Fisiológica/veterinária , Nociceptividade , Propanolaminas/administração & dosagem , Propanolaminas/farmacologia , Estudos Prospectivos , Infecções por Pseudomonas/tratamento farmacológico , Distribuição Aleatória , Choque Séptico/tratamento farmacológico , Suínos
15.
Expert Opin Biol Ther ; 18(10): 1049-1059, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30129371

RESUMO

INTRODUCTION: Stargardt macular dystrophy (STGD1) is a hereditary retinal degeneration that lacks effective treatment options. Gene therapy, stem cell therapy, and pharmacotherapy with visual cycle modulators (VCMs) and complement inhibitors are discussed as potential treatments. AREAS COVERED: Investigational therapies for STGD1 aim to reduce toxic bisretinoids and lipofuscin in the retina and retinal pigment epithelium (RPE). These agents include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Avacincaptad pegol is a C5 complement inhibitor that may reduce inflammation-related RPE damage. Animal models of STGD1 show promising data for these treatments, though proof of efficacy in humans is lacking. Fenretinide and emixustat are VCMs for dry AMD and STGD1 that failed to halt geographic atrophy progression or improve vision in trials for AMD. A1120 prevents retinol transport into RPE and may spare side effects typically seen with VCMs (nyctalopia and chromatopsia). Stem cell transplantation suggests potential biologic plausibility in a phase I/II trial. Gene therapy aims to augment the mutated ABCA4 gene, though results of a phase I/II trial are pending. EXPERT OPINION: Stem cell transplantation, ABCA4 gene therapy, VCMs, and complement inhibitors offer biologically plausible treatment mechanisms for treatment of STGD1. Further trials are warranted to assess efficacy and safety in humans.


Assuntos
Degeneração Macular/congênito , Terapias em Estudo/métodos , Terapias em Estudo/tendências , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Inativadores do Complemento/uso terapêutico , Terapia Genética/métodos , Terapia Genética/tendências , Humanos , Lipofuscina/uso terapêutico , Degeneração Macular/terapia , Éteres Fenílicos/uso terapêutico , Propanolaminas/uso terapêutico , Transplante de Células-Tronco
16.
Emerg Med J ; 35(9): 559-563, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29921621

RESUMO

OBJECTIVES: Beta blockers (ß-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, ß-blocker therapy in patients with cocaine-associated chest pain (CACP) continues to be an area of debate due to the potential risk of unopposed α-adrenergic stimulation and coronary vasospasm. Therefore, we performed a systematic review and meta-analysis of available studies to compare outcomes of ß-blocker versus no ß-blocker use among patients with CACP. METHODS: We searched the MEDLINE and EMBASE databases through September 2016 using the keywords 'beta blocker', 'cocaine' and commonly used ß-blockers ('atenolol', 'bisoprolol', 'carvedilol', 'esmolol', 'metoprolol' and 'propranolol') to identify studies evaluating ß-blocker use among patients with CACP. We specifically focused on studies comparing outcomes between ß-blocker versus no ß-blocker usage in patients with CACP. Studies without a comparison between ß-blocker and no ß-blocker use were excluded. Outcomes of interest included non-fatal myocardial infarction (MI) and all-cause mortality. Quantitative data synthesis was performed using a random-effects model and heterogeneity was assessed using Q and I2statistics. RESULTS: A total of five studies evaluating 1794 subjects were included. Overall, there was no significant difference on MI in patients with CACP on ß-blocker versus no ß-blocker (OR 1.36, 95% CI 0.68 to 2.75; p=0.39). Similarly, there was no significant difference in all-cause mortality in patients on ß-blocker versus no ß-blocker (OR 0.68, 95% CI 0.26 to 1.79; p=0.43). CONCLUSIONS: In patients presenting with acute chest pain and underlying cocaine, ß-blocker use does not appear to be associated with an increased risk of MI or all-cause mortality.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Cocaína/efeitos adversos , Síndrome Coronariana Aguda/etiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Atenolol/farmacologia , Atenolol/uso terapêutico , Bisoprolol/farmacologia , Bisoprolol/uso terapêutico , Carvedilol/farmacologia , Carvedilol/uso terapêutico , Humanos , Metoprolol/farmacologia , Metoprolol/uso terapêutico , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Propranolol/farmacologia , Propranolol/uso terapêutico
17.
Clin Nucl Med ; 43(8): 604-605, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29916915

RESUMO

A 37-year-old woman with pheochromocytoma underwent presurgical FDG PET/CT. Despite her usual antiadrenergic medication consisting in 25 mg of carvedilol, PET/CT demonstrated intense and widespread FDG uptake in brown adipose tissue (BAT). No BAT FDG uptake was detectable on a repeated examination after specific preparation consisting in 40 mg propranolol and 5 mg diazepam. We therefore recommend this propranolol-diazepam preparation in patients with pheochromocytoma referred for PET/CT. Carvedilol-classically prescribed to alleviate effects of adrenergic overstimulation-seems ineffective on BAT. This observation questions the benefit of carvedilol to reduce ß3-adrenoreceptor-mediated effects, not only in BAT, but also in other tissues.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/patologia , Antagonistas Adrenérgicos beta/farmacologia , Carbazóis/farmacologia , Feocromocitoma/tratamento farmacológico , Feocromocitoma/patologia , Propanolaminas/farmacologia , Tecido Adiposo Marrom/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Carbazóis/uso terapêutico , Carvedilol , Feminino , Fluordesoxiglucose F18 , Humanos , Feocromocitoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Propanolaminas/uso terapêutico , Falha de Tratamento
18.
Biomed Res Int ; 2018: 2691014, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670896

RESUMO

Our group has previously demonstrated that short-term treatment with esmolol reduces left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). The present study aimed to assess the molecular mechanisms related to this effect. Fourteen-month-old male SHRs were treated intravenously with saline as vehicle (SHR) or esmolol (SHR-E) (300 µg/kg/min). Age-matched vehicle-treated male Wistar-Kyoto (WKY) rats served as controls. After 48 hours of treatment, the hearts were harvested and left ventricular tissue was separated and processed for Western blot analysis to determine the levels of Akt, NF-κB, NFATc4, Creb1, Serca2a, Erk1/2, and Sapk/Jnk. Biomarkers of oxidative stress, such as catalase, protein carbonyls, total thiols, and total antioxidant capacity were evaluated. Esmolol reversed the levels of p-NFATc4, p-Akt, and p-NF-κB in SHRs to the phospholevels of these proteins in WKY rats without modifying p-Erk1/2, p-Sapk/Jnk, p-Creb1, or Serca2a in SHR. Compared with SHR, esmolol increased catalase activity and reduced protein carbonyls without modifying total thiols or total antioxidant capacity. Short-term treatment with esmolol reverses LVH in aged SHRs by downregulation of Akt/NF-κB and NFATc4 activity. Esmolol treatment also increases catalase activity and reduces oxidative stress in SHRs with LVH.


Assuntos
Envelhecimento/metabolismo , Hipertrofia Ventricular Esquerda/tratamento farmacológico , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Propanolaminas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antioxidantes/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Catalase/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Propanolaminas/administração & dosagem , Propanolaminas/farmacologia , Carbonilação Proteica/efeitos dos fármacos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Sístole/efeitos dos fármacos , Fatores de Tempo
19.
A A Pract ; 11(3): 63-67, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29634558

RESUMO

We describe a case of refractory pulseless polymorphic ventricular tachycardia successfully treated with a bolus of propranolol intravenously, followed by an esmolol infusion and extracorporeal life support for 4 days in a 12-year-old boy later diagnosed with catecholaminergic polymorphic ventricular tachycardia. He had an excellent neurological outcome. Genetic testing for mutations associated with cardiac arrhythmias yielded a mutation of the syntrophin α-1 gene. The pathogenicity of this specific variant is uncertain. A mutation of this gene at a different locus is implicated in rare cases of long-QT syndrome. The patient subsequently underwent left cardiac sympathetic denervation followed by implantable cardiac defibrillator insertion. He remains symptom and arrhythmia free on atenolol.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Proteínas de Ligação ao Cálcio , Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca/terapia , Proteínas de Membrana , Proteínas Musculares , Propranolol/uso terapêutico , Taquicardia Ventricular/terapia , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Antiarrítmicos/uso terapêutico , Atenolol/uso terapêutico , Proteínas de Ligação ao Cálcio/genética , Criança , Terapia Combinada , Desfibriladores Implantáveis , Eletrocardiografia , Parada Cardíaca/genética , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas Musculares/genética , Mutação , Propanolaminas/administração & dosagem , Propanolaminas/uso terapêutico , Propranolol/administração & dosagem , Simpatectomia , Taquicardia Ventricular/genética
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