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1.
Herzschrittmacherther Elektrophysiol ; 31(1): 73-76, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-32020271

RESUMO

BACKGROUND: The use of remote monitoring has increased due to recently published randomised studies. However, its benefit during acute rhythm disorders still remains controversial. OBJECTIVES: The current review describes the current status and highlights possible application of telemedicine during acute rhythm disorders. MATERIALS AND METHODS: The prerequisites, structural properties of the sender/patient and the receiver of the data/physician are examined and the results of the current literature are presented. RESULTS: Telemedicine during emergency rhythm disorders are normally reserved for specific scenarios. The lack of 24/7 staff of the receiver/hospital represents the main barrier. CONCLUSIONS: Remote medicine in the current form is not yet ready to be implemented for acute rhythm disorders. Expansion of currently existing chest pain units (CPUs) might enable this 24/7 service in the near future.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Emergências , Telemedicina , Dor no Peito , Serviço Hospitalar de Emergência , Humanos
2.
Lancet Haematol ; 7(2): e168-e176, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32004486

RESUMO

Tumour lysis syndrome is a complication of chemotherapy for haematological malignancies; in particular, aggressive leukaemias and lymphomas. For haematological malignancies, targeted therapies, such as small molecule inhibitors and monoclonal antibodies, have a high anti-tumour activity, are well tolerated, and have a low incidence of associated tumour lysis syndrome. The BCL-2 inhibitor venetoclax has a high anti-tumour activity in chronic lymphocytic leukaemia, achieving deep remissions by potently inducing apoptosis and increasing the risk for tumour lysis syndrome. In this Viewpoint, we discuss the pathophysiology, risk factors, monitoring, changes in laboratory parameters, and clinical manifestations of tumour lysis syndrome, and the prophylaxis and treatments available for this complication. Prophylaxis and treatment strategies have been implemented as standard of care in patients receiving venetoclax to minimise the risk of both laboratory and clinical manifestations of tumour lysis syndrome.


Assuntos
Antineoplásicos/efeitos adversos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Terapia de Alvo Molecular/efeitos adversos , Proteínas de Neoplasias/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Síndrome de Lise Tumoral/etiologia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Alopurinol/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/etiologia , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sinergismo Farmacológico , Humanos , Hiperfosfatemia/etiologia , Hiperfosfatemia/terapia , Hiperuricemia/tratamento farmacológico , Hiperuricemia/etiologia , Leucemia Linfocítica Crônica de Células B/enzimologia , Diálise Renal , Fatores de Risco , Índice de Gravidade de Doença , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/tratamento farmacológico , Síndrome de Lise Tumoral/prevenção & controle , Urato Oxidase/uso terapêutico
3.
Expert Opin Pharmacother ; 21(3): 339-352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31928092

RESUMO

Introduction: Heart failure (HF) affects over 6 million Americans and is the most common cause of hospital readmissions in the United States. Cardiac arrhythmias are common comorbidities seen in patients with HF and are associated with an increase in morbidity and mortality. Pharmacotherapeutic agents along with device and ablation therapies are the mainstays of treatment for cardiac arrhythmias in HF.Areas covered: An extensive literature review of articles and clinical trials on PUBMED on the topic of pharmacotherapy for cardiac arrhythmias in heart failure was conducted. This review article summarizes the above literature to describe the prevalence of the various types of arrhythmias in HF, the recommended pharmacotherapies for the treatment of these arrhythmias in HF and the evidence that supports these recommendations.Expert opinion: Cardiac arrhythmias are common in HF and are the leading cause of death in this patient population. The management of cardiac arrhythmias in HF is challenging. Pharmacotherapy is the primary though increasingly adjunctive therapy for most cardiac arrhythmias. Further, antiarrhythmic drugs must be used with caution in this patient population due to their potential adverse effects.


Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Estados Unidos
4.
Zhongguo Zhong Yao Za Zhi ; 44(18): 3842-3860, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31872715

RESUMO

Zhigancao decoction recorded in Treatise on Febrile Disease by Zhang Zhongjing in the Han dynasty have been widely used in treating palpitation and irregular pulse by traditional Chinese medicine physicians for thousands of years. It is all known that Zhigancao Decoction is used to treat consumptive disease. However,why it has been used to treat exogenous febrile disease? According to studies,Fumai Decoctions in Treatise on Differentiation and Treatment of Epidemic Febrile Disease,that was modified based on Zhigancao Decoction,have their names without reality. Serious defects,including unclear diagnosis,curative effect,and prognosis,have been found in ancient and modern medical records about Zhigancao Decoction. The indications of Zhigancao Decoction include atrial premature beats,ventricular premature beats,and viral myocarditis; tachyarrhythmia( supraventricular tachycardia,atrial fibrillation)with long interval or conduction block,during or after severe infection or high fever; chronic consumptive disease due to tumor after radiotherapy and chemotherapy,malignant fluid state of tumor,hematopathy,terminal stage of heart failure after major operation,and acute hemorrhage after control of severe infection and other major diseases; cough,phlegm and asthma due to chronic obstructive pulmonary disease,pulmonary interstitial fibrosis,lung cancer,after lung cancer surgery; increased heart rate and decreased blood pressure due to insufficient capacity after acute blood loss; the symptoms included palpitation,chest tightness,sweating,lassitude,lacking in strength,shortness of breath,syncope,sudden death,cough,expectoration,excessive phlegm,clear and dilute sputum,emaciation,dry and haggard skin,constipation,haemorrhagic,uterine bleeding,enjoy sweet taste,red tongue without moss,knotted pulse,intermittent pulse,thready rapid pulse,and weak pulse. Besides,Zhigancao Decoction has effect on cardioversion and maintenance of sinus rhythm without thrombosis in persistent atrial fibrillation and permanent atrial fibrillation. Zhigancao Decoction could stop bleeding soon for acute upper gastrointestinal bleeding,and achieve positivity of occult blood test; Zhigancao Decoction could promote thrombocytopenia for idiopathic thrombocytopenic purpura,with the number of platelets 1×109/L. Zhigancao Decoction could promote the rise of granulocytic,erythroid and megakaryocytic hematopoietic lines in unexplained severe anemia,thrombocytopenia,and leukocyte reduction. Zhigancao Decoction could treat cough,asthma,and chest tightness in lung cancer and after lung cancer surgery; chronic consumptive disease due to lung cancer after lung cancer surgery,hematopathy and acute blood loss,which all belonged to the scope of consumptive disease. Zhigancao Decoction could ascend platelets,which was considered as " oriental interleukins" for the ancients. Zhigancao Decoction possesses dual-directional regulation on anticoagulant and hemostasis,which was considered as " oriental low molecular heparin" and " oriental proton pump inhibitors". Large dose of Rehmannia glutinosa is the key of the efficacy of Zhigancao Decoction. This study is expected to enrich the guidelines for modern medical diagnosis and treatment. However,the clinical evidence,relevant genes and targeting network need to be deepened in future studies. In conclusion,it may be a shortcut to restore and explain Zhigancao Decoction formula syndromes based on modern pathophysiology and severe cases of critical care.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Cardioversão Elétrica , Plaquetas/citologia , Cuidados Críticos , Hemostasia , Humanos , Fitoterapia , Contagem de Plaquetas , Resultado do Tratamento
5.
Life Sci ; 239: 117075, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751587

RESUMO

AIMS: Arrhythmogenesis of chronic myocardial infarction (MI) is associated with the prolongation of action potential, reduction of inward rectifier potassium (IK1, Kir) channels and hyper-activity of Calcium/calmodulin-dependent kinase II (CaMKII) in cardiomyocytes. Zacopride, a selective IK1 agonist, was applied to clarify the cardioprotection of IK1 agonism via a CaMKII signaling on arrhythmias post-MI. METHODS: Male SD rats were implanted wireless transmitter in the abdominal cavity and subjected to left main coronary artery ligation or sham operation. The telemetric ECGs were monitored per day throughout 4 weeks. At the endpoint, isoproterenol (1.28 mg/kg, i.v.) was administered for provocation test. The expressions of Kir2.1 (dominant subunit of IK1 in ventricle) and CaMKII were detected by Western-blotting. KEY FINDINGS: In the telemetric rats post-MI, zacopride significantly reduced the episodes of atrioventricular conduction block (AVB), premature ventricular contraction (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF), without significant effect on superventricular premature contraction (SPVC). In provocation test, zacopride suppressed the onset of ventricular arrhythmias in conscious PMI or sham rats. The expression of Kir2.1 was significantly downregulated and p-CaMKII was upregulated post-MI, whereas both were restored by zacopride treatment. SIGNIFICANCE: IK1/Kir2.1 might be an attractive target for pharmacological controlling of lethal arrhythmias post MI.


Assuntos
Benzamidas/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Infarto do Miocárdio/fisiopatologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Potenciais de Ação , Animais , Arritmias Cardíacas/tratamento farmacológico , Benzamidas/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Eletrocardiografia/métodos , Ventrículos do Coração/metabolismo , Isoproterenol/farmacologia , Masculino , Miócitos Cardíacos/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Ratos , Ratos Sprague-Dawley , Taquicardia Ventricular/metabolismo
6.
Expert Opin Pharmacother ; 20(17): 2101-2114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31566420

RESUMO

Introduction: Ventricular arrhythmias are often seen in association with structural heart disease. However, approximately a tenth of affected patients have apparently normal hearts, where such arrhythmias typically occur in young patients, are sometimes inherited and can occasionally lead to sudden cardiac death (SCD). Over the past two decades, increased understanding of the underlying pathophysiology resulted in improved targeted pharmacological therapy.Areas covered: This article reviews current knowledge regarding drug therapy for inherited arrhythmia syndromes (Brugada, early repolarization, long QT and short QT syndromes, and catecholaminergic polymorphic ventricular tachycardia), and acquired arrhythmias (idiopathic ventricular fibrillation, short-coupled torsade de pointes, outflow tract ventricular tachycardia, idiopathic left, papillary muscle and annular ventricular tachycardias).Expert opinion: In inherited arrhythmia syndromes, appropriate clinical and genetic diagnoses followed by proper selection and dosing of antiarrhythmic drugs are of utmost importance to prevent SCD, most often without the need of implantable cardioverter-defibrillators. In acquired arrhythmias, appropriate pharmacotherapy in selected patients can also provide symptomatic relief and avoid the need for invasive therapy. Further research is needed to develop novel antiarrhythmic drugs or targeted therapy to increase efficacy and limit side effects.


Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Arritmias Cardíacas/genética , Arritmias Cardíacas/patologia , Síndrome de Brugada/tratamento farmacológico , Síndrome de Brugada/patologia , Estudos de Associação Genética , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/patologia , Quinidina/uso terapêutico , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/patologia
8.
Cardiol Clin ; 37(4): 459-468, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587787

RESUMO

Multiple cancer therapies are associated with cardiac arrhythmias through a variety of pathophysiologic mechanisms. Atrial fibrillation and atrial flutter are common during cancer therapy but should rarely limit continued delivery of therapy. Ventricular arrhythmias are not common during cancer therapy and are more often secondary to other cardiac pathologies. QT interval monitoring is recommended for some agents, although it is often not a reliable predictor of ventricular arrhythmias. Bradyarrhythmias are common and rarely require intervention, but special attention must be paid to heart block in checkpoint inhibitor therapy.


Assuntos
Antineoplásicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Cardiologia , Oncologia , Neoplasias/tratamento farmacológico , Arritmias Cardíacas/epidemiologia , Comorbidade , Saúde Global , Humanos , Neoplasias/epidemiologia
9.
AAPS PharmSciTech ; 20(8): 310, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520243

RESUMO

The production of 3D-printed dosage forms requires the preparation of high-quality filaments containing an active pharmaceutical ingredient (API). The objective of this research is to prepare filaments containing dronedarone hydrochloride, a drug used in the treatment of cardiac arrhythmias. Filaments and 3D-printed tablets were subjected to characterization methods in order to prove and ensure the stability of the API and preservation of the drug content. Blends containing different proportions of dronedarone hydrochloride (DNR), polyethylene glycol (PEG), and polyvinyl alcohol filament (PVA) were prepared in two forms: as a powder mixture and as a solid dispersion. Thermogravimetric analysis was conducted, and the thermal properties of the components and polymer blends were tested using differential scanning calorimetry. Hot melt extrusion at 170 °C was used to prepare the filaments, and the fused deposition modeling technique was employed to print tablets. Drug release profiles were obtained by in vitro tests. The results indicate that the mixture containing 10 wt.% of polyethylene glycol prepared as a solid dispersion exhibits the most straightforward structure and shows only the slightest deviation from the target filament diameter. The compact structure of the tablet obtained from the filament provides a uniform in vitro drug release over a 24-h period. It also shows the smallest aberration from the expected DNR content in the tablet. The paper demonstrates that a blend containing 10 wt.% of PEG, 10 wt.% of DNR, and 80 wt.% of PVA filament is the most appropriate formula for extrusion and tablet printing.


Assuntos
Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Dronedarona/administração & dosagem , Antiarrítmicos/química , Dronedarona/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Polietilenoglicóis , Álcool de Polivinil , Impressão Tridimensional , Solubilidade , Comprimidos
10.
J Pharmacol Sci ; 140(3): 284-290, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31481348

RESUMO

The human ether-a-go-go-related gene (hERG) encodes the K+ channel that carries the rapid component of the delayed rectifier current in the human heart. Reduction of hERG activity induced by gene mutations or pharmacological inhibition is responsible for the type 2 form of long QT syndrome in patients which can develop into ventricular arrhythmia and sudden cardiac death. Therefore, pharmacological activation of hERG may lead to therapeutic potential for cardiac arrhythmias. In this study we characterized a small and novel compound, N-(2-(tert-butyl)phenyl)-6-(4-chlorophenyl)-4-(trifluoromethyl) nicotinamide, HW-0168, that exhibits potent activation of hERG channel with an EC50 of 0.41 ± 0.2 µM. Using whole-cell patch clamp recording of HEK293 cells stably expressed hERG channels, we found that HW-0168 dramatically increased current amplitude about 2.5 folds and slowed down current inactivation about 4 folds. HW-0168 shifted the voltage-dependent channel activation to hyperpolarizing direction about 3.7 mV and the voltage-dependent channel inactivation to depolarizing direction about 9.4 mV. In addition, recording of guinea-pig ventricular cells confirmed that HW-0168 shortened the action potential duration. In conclusion, we identified a novel hERG channel activator HW-0168 that can be used for studying the physiological role of hERG in cardiac myocytes and may be beneficial for treating long QT syndrome.


Assuntos
Canais de Potássio Éter-A-Go-Go/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Linhagem Celular , Cobaias , Células HEK293 , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/metabolismo , Masculino
11.
Med Arch ; 73(2): 72-75, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31391690

RESUMO

Introduction: The most appropriate choice of pharmacological treatment of heart rhythm disorders occurring in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidity is often a topic of debate between pulmonologists and cardiologists in clinical practice, although numerous studies and clinical trials have demonstrated evidence to support the use of selective beta-blockers (BBs) in these patients. Aim: To examine the difference in the number of exacerbations in patients treated with a combination of verapamil and digoxin or BB alone in patients with different COPD stages. Patients and methods: The study included 68 patients (n = 68) diagnosed with COPD who were followed-up during a 12-month period, and the number of exacerbations were analyzed. The patients were divided into two groups according to the stage of COPD: GOLD II (moderate), and GOLD III (severe), and in each group a subdivision was established in relation to the use of either a combination of verapamil and digoxin or the use of BBs alone in pharmacological treatment. The inclusion criteria for patients were defined as following: a) established diagnosis of COPD according to present or deteriorated relevant clinical symptoms and signs, b) the ejection fraction (EF) of a left ventricle (LV) >35%, and c) spirometric cut-points classified as GOLD II (FEV1 / FVC <0.7, FEV1 predicted 50-80%), or GOLD III (FEV1/FVC <0.7, FEV1 predicted 30-50%) stage of the COPD. The exclusion criteria were EF of LV <35% and a lethal outcome during a follow-up period (2 patients were encountered). Exacerbation was defined as functional deterioration of the COPD symptoms verified by spirometric functional testing, frequency of hospitalizations according to GOLD stage assignment or verified clinical symptoms deterioration. Results: Regardless the pharmacological treatment, there is a statistically significant increase in the number of COPD exacerbations, in a 12-month period follow-up, in the GOLD III group (severe) compared to the GOLD II group (moderate). In the group of patients taking verapamil and digoxin, a two-tailed t-test was used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.01, and 2. In the group of patients taking BBs, a two-tailed t-test was also used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.003). Within the COPD GOLD II stage group, there appears to be no statistically significant difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 24) and the patients taking BBs alone (n = 15), although, in patients taking BBs alone, there appears to be a trend towards a decrease in the exacerbations compared to the number of exacerbations in patients taking verapamil and digoxin (p = 0.007). Within the COPD GOLD III stage group, there is no difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 20), and the patients taking BBs alone (n = 9), as analyzed by a two-tailed t-test, p = 0.577. Conclusion: Use of selective BBs in the treatment of cardiovascular comorbidity in patients with COPD represents a far better choice of pharmacological approach in the treatment of patients diagnosed with COPD GOLD II (moderate) stage.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Arritmias Cardíacas/epidemiologia , Bisoprolol/uso terapêutico , Estudos de Casos e Controles , Digoxina/uso terapêutico , Progressão da Doença , Volume Expiratório Forçado , Humanos , Metoprolol/uso terapêutico , Nebivolol/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Índice de Gravidade de Doença , Verapamil/uso terapêutico , Capacidade Vital
12.
Curr Protein Pept Sci ; 20(10): 996-1003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389311

RESUMO

Abstract:Throughout the last decade, extensive efforts have been devoted to developing a percutaneous catheter ablation and implantable cardioverter-defibrillator technique for patients suffering from ventricular arrhythmia. Antiarrhythmic drug efficacy for preventing arrhythmias remains disappointing because of adverse cardiovascular effects. Allocryptopine is an isoquinoline alkaloid widely present in medicinal herbs. Studies have indicated that allocryptopine exhibits potential anti-arrhythmic actions in various animal models. The potential therapeutic benefit of allocryptopine in arrhythmia diseases is addressed in this study, focusing on multiple ion channel targets and reduced repolarization dispersion. The limitations of allocryptopine research are clear given a lack of parameters regarding toxicology and pharmacokinetics and clinical efficacy in patients with ventricular arrhythmias. Much remains to be revealed about the properties of allocryptopine.


Assuntos
Antiarrítmicos , Arritmias Cardíacas/tratamento farmacológico , Alcaloides de Berberina , Plantas Medicinais/química , Traqueófitas/química , Animais , Antiarrítmicos/química , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/uso terapêutico , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
13.
J Physiol Pharmacol ; 70(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31443093

RESUMO

Standardized WS-1442 extract from Crataegus oxycantha (hawthorn) leaves and berries is one of the most widely studied preparations received from hawthorn. This popular substance is known from its positive influence on the cardiovascular system. The current research aimed to evaluate the optimal dose of standardized WS-1442 extract and the most beneficial period for its use. The study analysis was based on experiments previously conducted on male Sprague-Dawley rats (n = 152). The animals were divided into subgroups to examine the relationship between the dose-dependent (n = 96) and time-dependent (n = 56) effects of the mentioned extract. The research was performed based on the modified early reperfusion-induced arrhythmias model in vivo. The following parameters were assessed during the study: efficiency of mortality index reduction, reduction of ventricular arrhythmias incidences as well as the influence of standardized WS-1442 extract on hemodynamic parameters and amount of biochemical marker of cardiac tissue damage (creatine kinase). The current study revealed the dose- and time-dependent cardioprotective effect of standardized WS-1442 extract. It was expressed by mortality index reduction, decrease in the incidence and duration of severe ventricular arrhythmias and decline in the total amount of creatine kinase. Analyzed data coming from a model of reperfusion-induced arrhythmias in rats suggests that standardized WS-1442 extract is a potent cardioprotective agent whose action depends on both dose and intake time.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Crataegus/química , Flavonoides/farmacologia , Extratos Vegetais/farmacocinética , Animais , Arritmias Cardíacas/metabolismo , Cardiotônicos/farmacologia , Sistema Cardiovascular/metabolismo , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Masculino , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Reperfusão/métodos
14.
Int J Mol Sci ; 20(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443312

RESUMO

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. In basic studies, the regulation of autophagy has offered promising results for HCC treatment. This study aimed to address the question of whether amiodarone can improve survival rates in HCC patients associated with autophagy. Using datasets from the National Health Insurance Research Database, we enrolled patients over 18 years of age that had been diagnosed with HCC between January 1997 and December 2010. Amiodarone and non-amiodarone users were matched at a 1:1 frequency, according to all variables. Additionally, HepG2 cells treated with amiodarone were evaluated by cell viability and autophagic change. Autophagic signaling was examined by immunoblotting and tissue array immunohistochemistry. Of the 10,946 patients diagnosed with HCC, each cohort included 221 patients after 1:1 propensity score matching. The median survival was 36.70 months for the amiodarone users, and 24.48 months for the non-amiodarone users. After adjusting for age, gender, comorbidities and treatment, amiodarone users had a significantly lower risk of mortality. Amiodarone users also demonstrated an improved 3-year survival rate. Furthermore, amiodarone treatment-induced autophagy in HepG2 cells was demonstrated by autophagosome formation associated with increasing LC3B-II, P62, and Beclin-1 expression. Autophagic flux also increased following amiodarone treatment with bafilomycin A1. SiRNA of LC3B knocked down endogenous LC3B formation and restored HepG2 cell viability. This study provides epidemiologic evidence that amiodarone via autophagic degradation machinery may offer survival benefits for HCC patients with a history of arrhythmia. Further randomized, blinded, and placebo-controlled trials are warranted for patients with HCC.


Assuntos
Amiodarona/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Arritmias Cardíacas/tratamento farmacológico , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células Hep G2 , Humanos , Imuno-Histoquímica , Masculino , Modelos de Riscos Proporcionais , Transdução de Sinais/efeitos dos fármacos
15.
Nat Commun ; 10(1): 3476, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375661

RESUMO

Recent advances in DNA/RNA sequencing have made it possible to identify new targets rapidly and to repurpose approved drugs for treating heterogeneous diseases by the 'precise' targeting of individualized disease modules. In this study, we develop a Genome-wide Positioning Systems network (GPSnet) algorithm for drug repurposing by specifically targeting disease modules derived from individual patient's DNA and RNA sequencing profiles mapped to the human protein-protein interactome network. We investigate whole-exome sequencing and transcriptome profiles from ~5,000 patients across 15 cancer types from The Cancer Genome Atlas. We show that GPSnet-predicted disease modules can predict drug responses and prioritize new indications for 140 approved drugs. Importantly, we experimentally validate that an approved cardiac arrhythmia and heart failure drug, ouabain, shows potential antitumor activities in lung adenocarcinoma by uniquely targeting a HIF1α/LEO1-mediated cell metabolism pathway. In summary, GPSnet offers a network-based, in silico drug repurposing framework for more efficacious therapeutic selections.


Assuntos
Algoritmos , Reposicionamento de Medicamentos/métodos , Biologia de Sistemas/métodos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/genética , Simulação por Computador , Conjuntos de Dados como Assunto , Estudos de Viabilidade , Redes Reguladoras de Genes/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Saúde Holística , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Terapia de Alvo Molecular/métodos , Ouabaína/farmacologia , Ouabaína/uso terapêutico , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Fatores de Transcrição/metabolismo , Transcriptoma
16.
Med Clin North Am ; 103(5): 821-834, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31378328

RESUMO

The narrow therapeutic window of antiarrhythmic drugs makes their use clinically challenging. A solid understanding of the mechanisms of arrhythmias and how antiarrhythmics affect these mechanisms is only a preliminary step in their appropriate selection. Clinical factors, side-effect profiles, and proarrhythmic risks are more important than the cellular mechanisms of actions in drug selection and monitoring. This article provides a simplified approach to understanding cellular mechanisms and provides a practical approach to the selection and use of this important class of medications.


Assuntos
Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Potenciais de Ação , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/fisiopatologia , Humanos , Ablação por Radiofrequência , Medição de Risco
17.
Biomed Res Int ; 2019: 5269074, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317032

RESUMO

Adriamycin (Adr) is a cytotoxic anthracycline agent that is utilized to manage many types of tumors, but its clinical use is undesirable due to severe cardiotoxicity. The present study aimed to investigate the cardioprotective effect of Achillea fragrantissima (A. fragrantissima) against Adr-induced cardiotoxicity through the antioxidant and anti-inflammatory metabolic pathways. A single dose of Adr was injected in rats to induce cardiotoxicity. Rats are divided into 5 groups, control, A. fragrantissima 800, Adr, A. fragrantissima 400 + Adr, and A. fragrantissima 800 + Adr. 72 h after Adr administration, electrocardiographic (ECG) study was performed for all rats. Serum and hearts were then collected for biochemical and histopathological studies. A. fragrantissima ameliorated Adr-induced ST-segment elevation. It reduced Adr-induced elevation in lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), thiobarbituric acid reactive substance (TBARS), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and IL-6. It also protected against Adr-induced histopathological changes. Pretreatment with the extract increased heart tissue contents of glutathione peroxidase (GSH-PX) and reduced glutathione (GSH). Phytochemical analysis of the extract revealed that it is rich in phenolic and flavonoid active constituents. The results of this study revealed that A. fragrantissima extract ameliorates Adr-induced cardiotoxicity via an antioxidant and anti-inflammatory mechanisms. Further studies are warranted in order to recognize the precise active constituents of this natural extract which are responsible for the antioxidant and anti-inflammatory actions.


Assuntos
Achillea/química , Antioxidantes/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Cardiotoxicidade/tratamento farmacológico , Inflamação/tratamento farmacológico , Animais , Antioxidantes/química , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/patologia , Doxorrubicina/toxicidade , Glutationa , Coração/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos
18.
Eur J Pharmacol ; 859: 172488, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31233746

RESUMO

Cardiac arrhythmias are among the most important pathologies that lead to sudden death. The discovery of new therapeutic options against arrhythmias with low adverse effects is of paramount importance. Farnesol is found in essential oils with antioxidant, anti-inflammatory and cardioprotective properties. The aim of this work was to investigate the effects of farnesol on the contractile and electrophysiological properties in rat heart and evaluate its antiarrhythmic action. It was evaluated farnesol effects on the left ventricular developed pressure, ECG, potassium (Ik) and L-type Ca2+ currents (ICa,L), action potential, intracellular Ca2+ transient, Ca2+ sparks and waves and reactive oxygen species production. Antiarrhythmic activity of farnesol was determined in vivo and ex vivo. The results showed that 50 µM farnesol did not alter left ventricular developed pressure, heart rate, ECG parameters and intracellular Ca2+ transient but reduced ICa,L. Farnesol reduced action potential duration at 90% repolarization. Notably, farnesol improved arrhythmia score and the incidence of the most severe arrhythmias. Farnesol attenuated the generation of reactive oxygen species, Ca2+ sparks and waves in isolated cardiomyocytes submitted to Ca2+ overload. In conclusion, farnesol has antiarrhythmic effect mediated by reducing of ICa,L and IK along with a decrease of reactive oxygen species production and normalized Ca2+ sparks and waves.


Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Farneseno Álcool/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Tipo L/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Eletrocardiografia/efeitos dos fármacos , Farneseno Álcool/uso terapêutico , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Contração Miocárdica/efeitos dos fármacos , Oxigênio/metabolismo , Potássio/metabolismo , Ratos , Ratos Wistar , Disfunção Ventricular Esquerda/tratamento farmacológico
19.
Anesth Analg ; 129(1): 63-72, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31210652

RESUMO

BACKGROUND: Bupivacaine cardiotoxicity mainly manifests as inhibition of the cardiac sodium channel, which slows conduction, particularly at the ventricular level. Experimental studies have demonstrated that intravenous lipid emulsions (ILEs) can reduce the cardiotoxic effects of bupivacaine, but the extent of these effects is controversial. Sodium bicarbonate (B) represents the standard treatment of toxicity related to sodium channel-blocking drugs. The aim of this study was to compare the effects of ILEs and B on the speed of recovery from bupivacaine-induced effects on the electrocardiographic parameters. METHODS: Bupivacaine 4 mg/kg was administered to 24 anesthetized pigs. Three minutes after delivering the bupivacaine bolus, the animals were given the following: ILE 1.5 mL/kg followed by 0.25 mL/kg/min (ILE group) and B 2 mEq/kg followed by 1 mEq/kg/h (B group). Controls (C group) were given saline solution, 50 mL followed by 1 mL/kg/h. Electrophysiological parameters were evaluated in sinus rhythm and during right ventricular pacing at several time intervals up to 30 minutes. Data were analyzed as the area under the curve (AUC) for the first 10 minutes (AUC10) or 30 minutes (AUC30). RESULTS: Bupivacaine increased the sinus cycle length, PR interval, and QRS duration. AUC30 of the sinus rhythm QRS duration after antidote administration was significantly different among the 3 groups (P = .003). B group experienced faster recovery from intoxication than the C group (AUC10, P = .003; AUC30, P = .003) or the ILE group (AUC10, P = .018). During the first minute, 50% of the B group (versus 0% of the ILE and C groups) had recovered >30% of QRS duration (P = .011). The trend toward faster recovery in the ILE group than in the C group did not reach significance (AUC10, P = .23; AUC30, P = .06). Effects on the paced QRS duration at a rate of 150 bpm were more intense but with similar results (B versus C group: AUC10, P = .009; AUC30, P = .009; B versus ILE: AUC10, P = .015; AUC30, P = .024). The recovery process of the paced QRS tended to be slower for all antidotes. CONCLUSIONS: In a closed-chest swine model, B was an effective treatment for electrophysiological alterations caused by established bupivacaine toxicity. At clinical doses, B ameliorated bupivacaine electrocardiographic toxicity faster than ILE. Use-dependent effects of bupivacaine are prominent and delay the effects of both antidotes, but B produces faster recovery than ILE.


Assuntos
Anestésicos Locais , Antídotos/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Bupivacaína , Emulsões Gordurosas Intravenosas/administração & dosagem , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Bicarbonato de Sódio/administração & dosagem , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Cardiotoxicidade , Modelos Animais de Doenças , Sistema de Condução Cardíaco/fisiopatologia , Recuperação de Função Fisiológica , Sus scrofa , Fatores de Tempo
20.
PLoS One ; 14(6): e0217432, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31206521

RESUMO

BACKGROUND: Potassium replenishment protocols are often employed across broad patient populations to prevent cardiac arrhythmias. Tailoring potassium thresholds to specific patient populations would reduce unnecessary tasks and cost. The objective of this retrospective cohort study was to determine the threshold at which hypokalemia increases the risk for medically treated arrhythmias in cardiac versus medical and surgical intensive care units. METHODS: Patients captured in the publicly available Philips eICU database were assessed for initiation of either intravenous amiodarone, adenosine, ibutilide, isoproterenol, or lidocaine as a surrogate for a clinically significant arrhythmia. A landmark time-to-event analysis was conducted to investigate the association of serum potassium values and time-marked administration of an antiarrhythmic drug. Analysis was adjusted for comorbidities, the use of vasopressor agents, diuretics, as well as age, gender and severity of illness. RESULTS: Among 20,665 admissions to cardiac intensive care units, 1,371 (6.6%) were treated with either amiodarone, adenosine, ibutilide, isoproterenol, or lidocaine. For potassium values of ≥3.0<3.5mEq/L, antiarrhythmic treatment occurred at an increased rate compared to a baseline of ≥4.0≤5.0mEq/L (HR 1.23, 95% CI 1.01-1.51; P = 0.04). For admissions to medical and surgical intensive care units, 2,100 of 69,714 patients (3.0%) were treated with either amiodarone, adenosine, ibutilide, isoproterenol, or lidocaine. Potassium values of ≥3.0<3.5mEq/L were also associated with an increased hazard of treatment (HR 1.26, 95% CI 1.09-1.45; P = 0.002). In both cohorts, worsening hypokalemia was associated with an increased risk of antiarrhythmic drug treatment. In neither cohort were there statistically significant differences for serum potassium values of ≥3.5<4.0 and a baseline of ≥4.0≤5.0mEq/L. The proportion of patients initiated on vasopressors or inotropes was over four-fold higher in those treated with one of the antiarrhythmic drugs in both cohorts. CONCLUSIONS: Serum potassium levels <3.5mEq/L were associated with an increased hazard for treatment with specific antiarrhythmic drugs in a large cohort of patients admitted to both a cardiac as well as medical and surgical intensive care units. Potassium thresholds may be individualized further based on risk of relevant outcomes.


Assuntos
Antiarrítmicos , Arritmias Cardíacas , Cuidados Críticos , Bases de Dados Factuais , Hipopotassemia , Potássio/sangue , Idoso , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/sangue , Arritmias Cardíacas/tratamento farmacológico , Feminino , Humanos , Hipopotassemia/sangue , Hipopotassemia/induzido quimicamente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
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