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1.
Emerg Med Clin North Am ; 38(4): 755-769, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981615

RESUMO

There are approximately 350,000 out-of-hospital cardiac arrests and 200,000 in-hospital cardiac arrests annually in the United States, with survival rates of approximately 5% to 10% and 24%, respectively. The critical factors that have an impact on cardiac arrest survival include prompt recognition and activation of prehospital care, early cardiopulmonary resuscitation, and rapid defibrillation. Advanced life support protocols are continually refined to optimize intracardiac arrest management and improve survival with favorable neurologic outcome. This article focuses on current treatment recommendations for adult nontraumatic cardiac arrest, with emphasis on the latest evidence and controversies regarding intracardiac arrest management.


Assuntos
Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Manuseio das Vias Aéreas , Antiarrítmicos/administração & dosagem , Pressão Sanguínea , Dióxido de Carbono/análise , Diástole , Ecocardiografia , Cardioversão Elétrica , Serviço Hospitalar de Emergência , Epinefrina/administração & dosagem , Humanos , Hipotermia Induzida , Infusões Intraósseas , Infusões Intravenosas , Monitorização Fisiológica , Sistemas Automatizados de Assistência Junto ao Leito , Guias de Prática Clínica como Assunto , Vasoconstritores/administração & dosagem
2.
Medicine (Baltimore) ; 99(31): e21482, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756175

RESUMO

RATIONALE: In absence of conduction over the accessory pathway (AP) during the electrophysiological study, mapping and ablation is impossible. Various techniques can be used to activate absent conduction. In this presentation we describe the first case of latent AP ablation performed under continuous infusion of adenosine. PATIENT CONCERNS: A 65-year-old man, presented to emergency department with atrial fibrillation and antegrade conduction through a left lateral AP. He had palpitations and lightheadedness that occurred every 2 to 3 weeks. DIAGNOSIS: The electrophysiological study confirmed a latent left-side AP. INTERVENTIONS: Catheter ablation could not be performed because of absent conduction through AP. Therefore, a continuous infusion of adenosine was used to activate AP. Ablation was performed at the left lateral mitral ring. OUTCOMES: After catheter ablation and a new adenosine bolus there was no conduction through AP. LESSONS: In case of a latent AP when ablation is difficult to perform because of absent conduction at the time of electrophysiological study, adenosine can be used in doses of 1.5 mg/kg over 5 minutes continuous infusion.


Assuntos
Feixe Acessório Atrioventricular/cirurgia , Adenosina/administração & dosagem , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Feixe Acessório Atrioventricular/complicações , Idoso , Fibrilação Atrial/complicações , Humanos , Infusões Intra-Arteriais , Masculino
3.
Am J Emerg Med ; 38(9): 1879-1883, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32745920

RESUMO

OBJECTIVE: Intravenous push (IVP) diltiazem and metoprolol are commonly used for management of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). This study's objective was to determine if there was a significant difference in blood pressure reduction between agents. METHODS: This was a single-center, retrospective study of adult patients initially treated with IVP diltiazem or metoprolol in the ED from 2008 to 2018. Primary endpoint was mean reduction in systolic blood pressure (SBP) from baseline to nadir during the study period. Study period was defined as time from first dose of IVP intervention to 30 min after last dose of IVP intervention or first dose of maintenance therapy, whichever came first. RESULTS: A total of 63 diltiazem patients and 45 metoprolol patients met eligibility criteria. Baseline characteristics were similar except for initial ventricular rate (VR) and home beta-blocker use. Median dose of initial intervention was 10 [10-20] mg and 5 [5-5] mg for diltiazem and metoprolol respectively. Mean SBP reduction was 18 ± 22 mmHg for diltiazem compared to 14 ± 15 mmHg for metoprolol (p = .33). Clinically relevant hypotension was similar between groups 14% vs. 16% (p = .86). Rate control was achieved in 35 (56%) of the diltiazem group and 16 (36%) of the metoprolol group (p = .04). CONCLUSION: IVP diltiazem and metoprolol caused similar SBP reduction and hypotension when used for initial management of AF with RVR in the ED. However, rate control was achieved more often with diltiazem.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Diltiazem/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Metoprolol/uso terapêutico , Administração Intravenosa , Idoso , Antiarrítmicos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Diltiazem/administração & dosagem , Feminino , Humanos , Masculino , Metoprolol/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
J Interv Card Electrophysiol ; 59(2): 329-336, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32494896

RESUMO

BACKGROUND: Cardiovascular and arrhythmic events have been reported in hospitalized COVID-19 patients. However, arrhythmia manifestations and treatment strategies used in these patients have not been well-described. We sought to better understand the cardiac arrhythmic manifestations and treatment strategies in hospitalized COVID-19 patients through a worldwide cross-sectional survey. METHODS: The Heart Rhythm Society (HRS) sent an online survey (via SurveyMonkey) to electrophysiology (EP) professionals (physicians, scientists, and allied professionals) across the globe. The survey was active from March 27 to April 13, 2020. RESULTS: A total of 1197 respondents completed the survey with 50% of respondents from outside the USA, representing 76 countries and 6 continents. Of respondents, 905 (76%) reported having COVID-19-positive patients in their hospital. Atrial fibrillation was the most commonly reported tachyarrhythmia whereas severe sinus bradycardia and complete heart block were the most common bradyarrhythmias. Ventricular tachycardia/ventricular fibrillation arrest and pulseless electrical activity were reported by 4.8% and 5.6% of respondents, respectively. There were 140 of 631 (22.2%) respondents who reported using anticoagulation therapy in all COVID-19-positive patients who did not otherwise have an indication. One hundred fifty-five of 498 (31%) reported regular use of hydroxychloroquine/chloroquine (HCQ) + azithromycin (AZM); concomitant use of AZM was more common in the USA. Sixty of 489 respondents (12.3%) reported having to discontinue therapy with HCQ + AZM due to significant QTc prolongation and 20 (4.1%) reported cases of Torsade de Pointes in patients on HCQ/chloroquine and AZM. Amiodarone was the most common antiarrhythmic drug used for ventricular arrhythmia management. CONCLUSIONS: In this global survey of > 1100 EP professionals regarding hospitalized COVID-19 patients, a variety of arrhythmic manifestations were observed, ranging from benign to potentially life-threatening. Observed adverse events related to use of HCQ + AZM included prolonged QTc requiring drug discontinuation as well as Torsade de Pointes. Large prospective studies to better define arrhythmic manifestations as well as the safety of treatment strategies in COVID-19 patients are warranted.


Assuntos
Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/epidemiologia , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Inquéritos e Questionários , Arritmias Cardíacas/tratamento farmacológico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Estudos Transversais , Eletrocardiografia/métodos , Feminino , Humanos , Incidência , Síndrome do QT Longo/diagnóstico por imagem , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/epidemiologia , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Prognóstico , Índice de Gravidade de Doença , Taxa de Sobrevida , Torsades de Pointes/diagnóstico por imagem , Torsades de Pointes/tratamento farmacológico , Torsades de Pointes/epidemiologia , Resultado do Tratamento
5.
Life Sci ; 255: 117814, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32439300

RESUMO

AIMS: Amiodarone (AMIO) is currently used in medical practice to reverse ventricular tachycardia. Here we determine the effects of AMIO in the electromechanical properties of isolated left ventricle myocyte (LVM) from mice and guinea pig and in a cellular model of Long QT Syndrome Type 3 (LQTS-3) using anemone neurotoxin 2 (ATX II), which induces increase of late sodium current in LVM. MAIN METHODS AND KEY FINDINGS: Using patch-clamp technique, fluorescence imaging to detect cellular Ca2+ transient and sarcomere detection systems we evaluate the effect of AMIO in healthy LVM. AMIO produced a significant reduction in the percentage of sarcomere shortening (0.1, 1 and 10 µM) in a range of pacing frequencies, however, without significant attenuation of Ca2+ transient. Also, 10 µM of AMIO caused the opposite effect on action potential repolarization of mouse and guinea pig LVM. When LVM from mouse and guinea pig were paced in a range of pacing frequencies and exposed to ATX (10 nM), AMIO (10 µM) was only able to abrogate electromechanical arrhythmias in LVM from guinea pig at lower pacing frequency. SIGNIFICANCE: AMIO has negative inotropic effect with opposite effect on action potential waveform in mouse and guinea pig LVM. Furthermore, the antiarrhythmic action of AMIO in LQTS-3 is species and frequency-dependent, which indicates that AMIO may be beneficial for some types of arrhythmias related to late sodium current.


Assuntos
Amiodarona/farmacologia , Antiarrítmicos/farmacologia , Doença do Sistema de Condução Cardíaco/tratamento farmacológico , Síndrome do QT Longo/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Amiodarona/administração & dosagem , Animais , Antiarrítmicos/administração & dosagem , Doença do Sistema de Condução Cardíaco/fisiopatologia , Relação Dose-Resposta a Droga , Cobaias , Ventrículos do Coração/citologia , Síndrome do QT Longo/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Técnicas de Patch-Clamp , Sarcômeros/efeitos dos fármacos , Sarcômeros/metabolismo , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/metabolismo , Especificidade da Espécie
7.
Am J Emerg Med ; 38(7): 1541.e3-1541.e4, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32278568

RESUMO

Paroxysmal supraventricular tachycardia (PSVT) is one of the more common arrhythmias requiring treatment in the emergency department. Intravenous adenosine is recommended as the initial medication of choice for treatment of PSVT, given in escalating doses up to a maximum of 12 mg. With a serum half-life of less than 10 s, adenosine must be given rapidly to allow for adequate time for it to reach the heart via venous return. In over 10% of adult patients, PSVT will not be terminated with maximum doses of adenosine. We report a case of a patient requiring a higher-than recommended dose of adenosine for termination of PSVT. The patient had a history of pulmonary hypertension with resultant right heart failure at the time of presentation. We believe the higher dose of adenosine was necessary in this patient because of the impaired venous return to her right heart. This case indicates that patients with impaired venous return to the right heart may require higher-than-recommended doses of adenosine for effective termination of PSVT.


Assuntos
Adenosina/administração & dosagem , Antiarrítmicos/administração & dosagem , Taquicardia Paroxística/tratamento farmacológico , Taquicardia Supraventricular/tratamento farmacológico , Relação Dose-Resposta a Droga , Eletrocardiografia , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão Pulmonar/complicações , Pessoa de Meia-Idade
8.
J Cardiovasc Pharmacol Ther ; 25(3): 226-231, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32008366

RESUMO

BACKGROUND: Although there is strong evidence supporting the use of statin therapy after myocardial infarction (MI), some mechanistic gaps exist regarding the benefits of this therapy at the very onset of MI. Among the potential beneficial mechanisms, statins may improve myocardial electrical stability and reduce life-threatening ventricular arrhythmia, as reported in stable clinical conditions. This study was designed to evaluate whether this mechanism could also occur during the acute phase of MI. METHODS: Consecutive patients with ST-segment elevation MI were treated without statin (n = 57) or with a simvastatin dose of 20 to 80 mg (n = 87) within the first 24 hours after MI symptom onset. Patients underwent digital electrocardiography within the first 24 hours and at the third and fifth days after MI. The QTC dispersion (QTcD) was measured both with and without the U waves. RESULTS: Although QTcD values were equivalent between the groups at the first day (80.6 ± 36.0 vs 80.0 ± 32.1; P = 0.36), they were shorter among individuals using simvastatin than in those receiving no statins on the third (90.4 ± 38.6 vs 86.5 ± 36.9; P = .036) and fifth days (73.1 ± 31 vs 69.2 ± 32.6; P = .049). We obtained similar results when analyzing the QTcD duration including the U wave. All values were adjusted by an ANCOVA model after propensity-score matching. CONCLUSIONS: Statins administered within 24 hours of ST-segment elevation MI reduced QTc dispersion, which may potentially attenuate the substrate for life-threatening ventricular arrhythmias.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/prevenção & controle , Frequência Cardíaca/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Sinvastatina/administração & dosagem , Idoso , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Esquema de Medicação , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Sinvastatina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
9.
Am J Trop Med Hyg ; 102(4): 797-799, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32043461

RESUMO

Chronic Chagas heart disease has different clinical manifestations including arrhythmias, heart failure, and stroke. Chest pain is one of the most common symptoms and when associated with changes in the electrocardiogram, such as T-wave changes, electrically inactive areas, and segmental wall motion abnormalities, may lead to a misdiagnosis of acute coronary syndrome (ACS). Here, we describe two patients with Chagas heart disease and syncope due to sustained ventricular tachycardia who were misdiagnosed with ACS, and discuss the role of novel imaging modalities in the differential diagnosis and risk stratification.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatia Chagásica/complicações , Idoso , Amiodarona/administração & dosagem , Amiodarona/uso terapêutico , Antiarrítmicos/administração & dosagem , Antiarrítmicos/uso terapêutico , Clopidogrel/administração & dosagem , Clopidogrel/uso terapêutico , Desfibriladores Implantáveis , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico
10.
J Am Soc Nephrol ; 31(3): 637-649, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32079604

RESUMO

BACKGROUND: Because stroke prevention is a major goal in the management of ESKD hemodialysis patients with atrial fibrillation, investigating racial/ethnic disparities in stroke among such patients is important to those who could benefit from strategies to maximize preventive measures. METHODS: We used the United States Renal Data System to identify ESKD patients who initiated hemodialysis from 2006 to 2013 and then identified those with a subsequent atrial fibrillation diagnosis and Medicare Part A/B/D. Patients were followed for 1 year for all-cause stroke, mortality, prescription medications, and cardiovascular disease procedures. The survival mediational g-formula quantified the percentage of excess strokes attributable to lower use of atrial fibrillation treatments by race/ethnicity. RESULTS: The study included 56,587 ESKD hemodialysis patients with atrial fibrillation. Black, white, Hispanic, and Asian patients accounted for 19%, 69%, 8%, and 3% of the population, respectively. Compared with white patients, black, Hispanic, or Asian patients were more likely to experience stroke (13%, 15%, and 16%, respectively) but less likely to fill a warfarin prescription (10%, 17%, and 28%, respectively). Warfarin prescription was associated with decreased stroke rates. Analyses suggested that equalizing the warfarin distribution to that in the white population would prevent 7%, 10%, and 12% of excess strokes among black, Hispanic, and Asian patients, respectively. We found no racial/ethnic disparities in all-cause mortality or use of cardiovascular disease procedures. CONCLUSIONS: Racial/ethnic disparities in all-cause stroke among hemodialysis patients with atrial fibrillation are partially mediated by lower use of anticoagulants among black, Hispanic, and Asian patients. The reasons for these disparities are unknown, but strategies to maximize stroke prevention in minority hemodialysis populations should be further investigated.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Disparidades em Assistência à Saúde/etnologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Antiarrítmicos/administração & dosagem , Anticoagulantes/administração & dosagem , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Estudos de Coortes , Bases de Dados Factuais , Grupos Étnicos/estatística & dados numéricos , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Medicare/estatística & dados numéricos , Racismo , Diálise Renal/métodos , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos
11.
J Cardiovasc Pharmacol ; 75(4): 276-283, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032206

RESUMO

Pharmacologic management of atrial fibrillation (AF) is a pressing problem. This arrhythmia afflicts >5 million individuals in the United States and prevalence is estimated to rise to 12 million by 2050. Although the pill-in-the-pocket regimen for self-administered AF cardioversion introduced over a decade ago has proven useful, significant drawbacks exist. Among these are the relatively long latency of effects in the range of hours along with potential for hypotension and other adverse effects. This experience prompted development of a new strategy for increasing plasma concentrations of antiarrhythmic drugs rapidly and for a limited time, namely, pulmonary delivery. In preclinical studies in Yorkshire pigs, intratracheal administration of flecainide was shown to cause a rapid, reproducible increase in plasma drug levels. Moreover, pulmonary delivery of flecainide converted AF to normal sinus rhythm by prolonging atrial depolarization, which slows intra-atrial conduction and seems to be directly correlated with efficacy in converting AF. The rapid rise in plasma flecainide levels optimizes its anti-AF effects while minimizing adverse influences on ventricular depolarization and contractility. A more concentrated and soluble formulation of flecainide using a novel cyclodextrin complex excipient reduced net drug delivery for AF conversion when compared to the acetate formulation. Inhalation of the beta-adrenergic blocking agent metoprolol slows ventricular rate and can also terminate AF. In human subjects, oral inhalation of flecainide acetate with a hand-held, breath-actuated nebulizer results in signature prolongation of the QRS complex without serious adverse events. Thus, pulmonary delivery is a promising advance in pharmacologic approach to management of AF.


Assuntos
Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Flecainida/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Metoprolol/administração & dosagem , Administração por Inalação , Animais , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacocinética , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Modelos Animais de Doenças , Composição de Medicamentos , Flecainida/efeitos adversos , Flecainida/farmacocinética , Humanos , Metoprolol/efeitos adversos , Metoprolol/farmacocinética , Nebulizadores e Vaporizadores , Resultado do Tratamento
12.
Arch Cardiol Mex ; 90(1): 69-76, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31996856

RESUMO

Atrial fibrillation (AF) is a frequent arrhythmia; its prevalence is near 2% in the general population; in Mexico, more than one-half million people are affected. AF needs to be considered as a public health problem. Because AF is an independent risk factor associated with mortality, due to embolic events, heart failure, or sudden death; early diagnosis is of utmost importance. In unstable patients with a recent onset of AF, electrical cardioversion should be practiced. In stable patients, once thromboembolic measures have been taken, it is necessary to assess whether it is reasonable to administer an antiarrhythmic drug to restore sinus rhythm or performed electrical cardioversion. For recidivating cases of paroxysmal and persistent presentation, the most effective strategy is performed pulmonary vein isolation with either radiofrequency or cryoballoon energy. Permanent AF is that in which recovery of sinus rhythm is not possible, the distinguishing feature of this phase is the uncontrollable variability of the ventricular frequency and could be treated pharmacologically with atrioventricular (AV) nodal blockers or with a VVIR pacemaker plus AV nodal ablation. The presence of AF has long been associated with the development of cerebral and systemic (pulmonary, limb, coronary, renal, and visceral) embolism. The prevention of embolisms in "valvular" AF should perform with Vitamin K antagonists (VKA). For patients with AF not associated with mitral stenosis or a mechanical valve prosthesis, a choice can be made between anticoagulant drugs, VKA, or direct oral anticoagulants. Antiplatelet agents have the weakest effect in preventing embolism.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/terapia , Tromboembolia/prevenção & controle , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Criocirurgia/métodos , Cardioversão Elétrica/métodos , Fibrinolíticos/administração & dosagem , Humanos , México/epidemiologia , Ablação por Radiofrequência/métodos , Fatores de Risco , Tromboembolia/etiologia
13.
Basic Res Cardiol ; 115(2): 9, 2020 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-31900593

RESUMO

Ventricular arrhythmia is the most common cause of sudden cardiac death in patients with myocardial infarction (MI). Fibroblast growth factor 21 (FGF21) has been shown to play an important role in cardiovascular and metabolic diseases. However, the effects of FGF21 on ventricular arrhythmias following MI have not been addressed yet. The present study was conducted to investigate the pharmacological action of FGF21 on ventricular arrhythmias after MI. Adult male mice were administrated with or without recombinant human basic FGF21 (rhbFGF21), and the susceptibility to arrhythmias was assessed by programmed electrical stimulation and optical mapping techniques. Here, we found that rhbFGF21 administration reduced the occurrence of ventricular tachycardia (VT), improved epicardial conduction velocity and shorted action potential duration at 90% (APD90) in infarcted mouse hearts. Mechanistically, FGF21 may improve cardiac electrophysiological remodeling as characterized by the decrease of INa and IK1 current density in border zone of infarcted mouse hearts. Consistently, in vitro study also demonstrated that FGF21 may rescue oxidant stress-induced dysfunction of INa and IK1 currents in cultured ventricular myocytes. We further found that oxidant stress-induced down-regulation of early growth response protein 1 (EGR1) contributed to INa and IK1 reduction in post-infarcted hearts, and FGF21 may recruit EGR1 into the SCN5A and KCNJ2 promoter regions to up-regulate NaV1.5 and Kir2.1 expression at transcriptional level. Moreover, miR-143 was identified as upstream of EGR1 and mediated FGF21-induced EGR1 up-regulation in cardiomyocytes. Collectively, rhbFGF21 administration effectively suppressed ventricular arrhythmias in post-infarcted hearts by regulating miR-143-EGR1-NaV1.5/Kir2.1 axis, which provides novel therapeutic strategies for ischemic arrhythmias in clinics.


Assuntos
Antiarrítmicos/administração & dosagem , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Fatores de Crescimento de Fibroblastos/administração & dosagem , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , MicroRNAs/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Taquicardia Ventricular/prevenção & controle , Potenciais de Ação/efeitos dos fármacos , Animais , Células Cultivadas , Modelos Animais de Doenças , Proteína 1 de Resposta de Crescimento Precoce/genética , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Proteínas Recombinantes/administração & dosagem , Transdução de Sinais , Taquicardia Ventricular/genética , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/fisiopatologia
14.
J Cardiovasc Pharmacol Ther ; 25(1): 65-71, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31242756

RESUMO

Ranolazine has been found to prevent ventricular arrhythmias (VAs) during acute myocardial infarction (AMI). This study aimed to investigate its efficacy on VAs induced several days post-MI. For this purpose, 13 anesthetized rabbits underwent coronary artery ligation. Ten of these animals that survived AMI were reanesthetized 3 to 7 days later for electrophysiologic testing. An endocardial monophasic action potential combination catheter was placed in the right ventricle for simultaneous pacing and recording. Monophasic action potential duration, ventricular effective refractory period (VERP), and VAs induced by programmed stimulation were assessed. Measurements were performed during control pacing, and following an intravenous infusion of either a low-dose ranolazine (2.4 mg/kg, R1) or a higher dose ranolazine (4.8 mg/kg cumulative dose, R2). During control stimulation, 2 animals developed primary ventricular fibrillation (VF), 6 sustained ventricular tachycardia (sVT), and 2 nonsustained VT (nsVT). R1 did not prevent the appearance of VAs in any of the experiments; in contrast, it aggravated nsVT into sVT and complicated sVT termination in 2 of 6 animals. Sustained ventricular tachycardia cycle length and VERP were only slightly decreased after R1 (112 ± 5 vs 110 ± 6 ms and 101 ± 11 vs 98 ± 10 ms, respectively). R2 suppressed inducibility of control nsVT, VF, and sVT in 2 animals. In 4 animals with still inducible sVT, R2 significantly prolonged VT cycle length by 150 ± 23 ms (P < .01), and VERP by 120 ± 7 ms (P < .001) versus control. In conclusion, R2 exerted antiarrhythmic efficacy against subacute-MI VAs, whereas R1 rather aggravated than prevented these arrhythmias. Ventricular effective refractory period prolongation could partially explain the antiarrhythmic action of R2 in this rabbit model.


Assuntos
Antiarrítmicos/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Ranolazina/administração & dosagem , Taquicardia Ventricular/prevenção & controle , Fibrilação Ventricular/prevenção & controle , Potenciais de Ação/efeitos dos fármacos , Animais , Antiarrítmicos/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/fisiopatologia , Coelhos , Ranolazina/toxicidade , Período Refratário Eletrofisiológico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/fisiopatologia
15.
J Cardiovasc Pharmacol ; 75(1): 64-74, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31842025

RESUMO

Acute statin therapy reduces myocardial ischemia/reperfusion (IR) injury-induced ventricular fibrillation (VF), but the underlying electrophysiological mechanisms remain unclear. This study sought to investigate the antiarrhythmic effects of a single bolus rosuvastatin injection in failing rabbit hearts with IR injury and to unveil the underlying molecular mechanisms. Rabbits were divided into rosuvastatin, rosuvastatin + L-NAME, control, and L-NAME groups. Intravenous bolus rosuvastatin (0.5 mg/kg) and/or L-NAME (10 mg/kg) injections were administered 1 hour and 15 minutes before surgery, respectively. Heart failure was induced using rapid ventricular pacing. Under general anesthesia with isoflurane, an IR model was created by coronary artery ligation for 30 minutes, followed by reperfusion for 15 minutes. Plasma NO end product levels were measured during IR. Then, hearts were excised and Langendorff-perfused for optical mapping studies. Cardiac tissues were sampled for Western blot analysis. Rosuvastatin increased plasma NO levels during IR, which was abrogated by L-NAME. Spontaneous VF during IR was suppressed by rosuvastatin (P < 0.001). Intracellular calcium (Cai) decay and conduction velocity were significantly slower in the IR zone. Rosuvastatin accelerated Cai decay, ameliorated conduction inhomogeneity, and reduced the inducibility of spatially discordant alternans and VF significantly. Western blots revealed significantly higher expression of enhancing endothelial NO-synthase and phosphorylated enhancing endothelial NO-synthase proteins in the Rosuvastatin group. Furthermore, SERCA2a, phosphorylated connexin43, and phosphorylated phospholamban were downregulated in the IR zone, which was attenuated or reversed by rosuvastatin. Acute rosuvastatin therapy before ischemia reduced IR-induced VF by improving SERCA2a function and ameliorating conduction disturbance in the IR zone.


Assuntos
Antiarrítmicos/administração & dosagem , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Conexina 43/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Fibrilação Ventricular/prevenção & controle , Potenciais de Ação , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Preparação de Coração Isolado , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Coelhos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Fatores de Tempo , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/fisiopatologia
16.
Indian J Pharmacol ; 51(5): 296-301, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31831918

RESUMO

Nicorandil is a well-known antianginal agent, which has been recommended as one of the second-line treatments for chronic stable angina as justified by the European guidelines. It shows an efficacy equivalent to that of classic antianginal agents. Nicorandil has also been applied clinically in various cardiovascular diseases such as variant or unstable angina and reperfusion-induced damage following coronary angioplasty or thrombolysis. Different mechanisms have been involved in the protective effects of nicorandil in various diseases through either opening of adenosine triphosphate-sensitive potassium (KATP) channel or donation of nitric oxide (NO). The predominance or participation of any of these proposed mechanisms depends on the dose of nicorandil used, the location of diseased conditions, and if this mechanism is still functioning or not. The protection afforded by nicorandil has been shown to be mainly attributed to KATP channel opening in experimental models of myocardial and pulmonary fibrosis as well as renal injury or glomerulonephritis, whereas NO donation predominates as a mechanism of protection in hepatic fibrosis and inflammatory bowel diseases. Therefore, in different diseased conditions, it is important to know which mechanism plays the major role in nicorandil-induced curative or protective effects. This can bring new insights into the proper use of selected medication and its recommended dose for targeting certain disease.


Assuntos
Antiarrítmicos/administração & dosagem , Nicorandil/administração & dosagem , Angina Estável/tratamento farmacológico , Animais , Antiarrítmicos/farmacologia , Relação Dose-Resposta a Droga , Humanos , Canais KATP/efeitos dos fármacos , Canais KATP/metabolismo , Nicorandil/farmacologia , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/farmacologia
17.
BMJ Case Rep ; 12(12)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31796445

RESUMO

Trigeminocardiac reflex (TCR) is a brainstem reflex triggered by the stimulation of any branch of the fifth cranial nerve along its course, presenting as a reduction in heart rate and blood pressure. Oculocardiac reflex is a well-known subtype of TCR. In the case reported here, remarkable arrhythmia followed by bradycardia occurred suddenly in a healthy patient undergoing orthognathic surgery. The heart rhythm recovered when the surgical manipulation ceased, but bradycardia was reproduced when the surgery resumed. This case of TCR is unique in that remarkable arrhythmia first appeared and led to bradycardia; accordingly, intravenous lidocaine and an anticholinergic agent were administered simultaneously instead of anticholinergic agents alone, and were protective. Although TCR rarely occurs during orthognathic surgery, clinicians should be aware of its possibility and able to judge and manage it promptly.


Assuntos
Bradicardia/etiologia , Complicações Intraoperatórias/etiologia , Procedimentos Cirúrgicos Ortognáticos/efeitos adversos , Osteotomia Sagital do Ramo Mandibular/efeitos adversos , Reflexo Trigêmino-Cardíaco/fisiologia , Administração Intravenosa , Antiarrítmicos/administração & dosagem , Bradicardia/tratamento farmacológico , Antagonistas Colinérgicos/administração & dosagem , Eletrocardiografia , Humanos , Complicações Intraoperatórias/tratamento farmacológico , Lidocaína/administração & dosagem , Masculino , Procedimentos Cirúrgicos Ortognáticos/métodos , Osteotomia Sagital do Ramo Mandibular/métodos , Reflexo Trigêmino-Cardíaco/efeitos dos fármacos , Adulto Jovem
18.
BMC Oral Health ; 19(1): 271, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801491

RESUMO

BACKGROUND: It is essential to accomplish the appropriate emergency care particularly in patients undergoing stressful dento-oral surgical procedures. Atrial flutter may be induced by sympathetic hypertonia due to excessive mental and physical stress. There is no report regarding dental care in patients with atrial flutter. Herein, we describe a rare case of the antiarrhythmic management in an outpatient who presented with an electrocardiographic finding of paroxysmal atrial flutter before the initiation of the dento-oral surgical procedure. CASE PRESENTATION: A 60-year-old male patient was scheduled for a dental extraction. He had a history of angina pectoris, diabetes mellitus, and paroxysmal atrial fibrillation with medication. The preoperative electrocardiogram (ECG) revealed left ventricular hypertrophy and ST-T segment abnormality. Immediately before the dental extraction, II-lead ECG revealed atrial flutter; however, he complained of few subjective symptoms, such as precordial discomfort or palpitation. Observing the vital signs, ECG findings, and the general condition of the patient, low dose diltiazem was immediately administered by continuous infusion in order to control the heart rate and prevent atrial flutter-induced supraventricular tachyarrhythmia. Special attention was paid to prevent any critical cardiovascular condition under a preparation of intravenous disopyramide and verapamil and a defibrillator. The intravenous administration of diltiazem progressively restored the sinus rhythm after converting atrial flutter into atrial fibrillation, resulting in the prevention of tachycardia, and then was found to be appropriate as a prophylactic therapy of tachyarrhythmia. CONCLUSIONS: The present case suggests that it is possible to successfully manage some of such patients using our method during dento-oral surgery which is likely to be associated with mental and physical stress. Therefore, it is essential to accomplish an initial emergency care in parallel to the differential diagnosis of unforeseen serious medical conditions or paroxysmal arrhythmia such as atrial flutter.


Assuntos
Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Flutter Atrial/tratamento farmacológico , Diltiazem/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Taquicardia Supraventricular/prevenção & controle , Fibrilação Atrial/fisiopatologia , Flutter Atrial/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Assistência Odontológica , Diltiazem/uso terapêutico , Eletrocardiografia Ambulatorial , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Bucais , Pacientes Ambulatoriais , Taquicardia Paroxística/tratamento farmacológico , Taquicardia Paroxística/fisiopatologia , Taquicardia Supraventricular/fisiopatologia
19.
Scand J Trauma Resusc Emerg Med ; 27(1): 109, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823800

RESUMO

BACKGROUND: The 2015 AHA guidelines recommend that amiodarone should be used for patients with refractory ventricular fibrillation (RVF). However, the optimal time interval between the incoming call and amiodarone administration (call-to-amiodarone administration interval) in RVF patients has not been investigated. We hypothesized that the time elapsed until amiodarone administration could affect the neurological outcome at hospital discharge in patients with RVF. METHODS AND RESULTS: This study is a retrospective analysis of prospectively collected data. One hundred thirty-four patients were enrolled. In univariate logistic regression, the probability of a good neurological outcome at hospital discharge decreased as the time elapsed until amiodarone administration increased (OR 0.89 [95% CI = 0.80-0.99]). In multivariate logistic regression, the patients who were administered amiodarone in less than 20 min showed higher rates of prehospital ROSC, survival at hospital arrival, any ROSC, survival at admission, survival to discharge, and good CPC at hospital discharge. The call-to-amiodarone administration interval of ≤20 min (OR 6.92, 95% CI 1.72-27.80) was the independent factor affecting the neurological outcome at hospital discharge. CONCLUSION: Early amiodarone administration (≤ 20 min) showed better neurological outcome at hospital discharge for OHCA patients who showed initial ventricular fibrillation and subsequent RVF.


Assuntos
Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Parada Cardíaca Extra-Hospitalar , Avaliação de Resultados em Cuidados de Saúde , Fibrilação Ventricular/tratamento farmacológico , Idoso , Reanimação Cardiopulmonar , Serviços Médicos de Emergência/métodos , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/mortalidade , Alta do Paciente , Estudos Retrospectivos
20.
Mar Drugs ; 17(12)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31817438

RESUMO

Severe arrhythmias-such as ventricular arrhythmias-can be fatal, but treatment options are limited. The effects of a combined formulation of tetrodotoxin (TTX) and lidocaine (LID) on severe arrhythmias were studied. Patch clamp recording data showed that the combination of LID and TTX had a stronger inhibitory effect on voltage-gated sodium channel 1.5 (Nav1.5) than that of either TTX or LID alone. LID + TTX formulations were prepared with optimal stability containing 1 µg of TTX, 5 mg of LID, 6 mg of mannitol, and 4 mg of dextran-40 and then freeze dried. This formulation significantly delayed the onset and shortened the duration of arrhythmia induced by aconitine in rats. Arrhythmia-originated death was avoided by the combined formulation, with a decrease in the mortality rate from 64% to 0%. The data also suggests that the anti-arrhythmic effect of the combination was greater than that of either TTX or LID alone. This paper offers new approaches to develop effective medications against arrhythmias.


Assuntos
Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Lidocaína/administração & dosagem , Tetrodotoxina/administração & dosagem , Animais , Antiarrítmicos/farmacologia , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Modelos Animais de Doenças , Combinação de Medicamentos , Estabilidade de Medicamentos , Excipientes/química , Feminino , Liofilização , Lidocaína/farmacologia , Masculino , Canal de Sódio Disparado por Voltagem NAV1.5/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Tetrodotoxina/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/administração & dosagem , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia
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