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1.
Anesth Analg ; 129(4): 1124-1129, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31584918

RESUMO

BACKGROUND: Sugammadex, with its novel mechanism of action of encapsulation and noncompetitive binding of aminosteroid neuromuscular-blocking agents (rocuronium and vecuronium), may offer distinct advantage to pediatric patients where residual neuromuscular blockade may be poorly tolerated. Data describing its use in the pediatric population are limited, and no large-scale studies are available evaluating the occurrence of adverse event across the full spectrum of ages. We sought to measure the occurrence of adverse events, assess the severity and clinical significance of the events, and quantify a surrogate measure of efficacy of sugammadex compared to neostigmine in a large population and in the full age range of children. METHODS: Beginning in September 2016 through initiation of data collection, we identified from our data warehouse that all patients were treated with sugammadex for reversal of neuromuscular blockade, from birth through adolescence, and retrospectively matched, by case type and age group, to historical neostigmine-treated controls. From subsequent chart review, we quantified occurrence of adverse events and administration of medications to treat adverse events. All cases in the originally identified cohort treated with epinephrine after administration of sugammadex underwent chart review to elicit the cause, in the event that an infrequently occurring event was not captured after the case-matching process. "End-Interval Time," the time from administration of reversal agent to time out of the procedure room, was measured as an indirect assessment of efficacy. RESULTS: Fewer cases of bradycardia were observed in the sugammadex group compared to the neostigmine group in the overall cohort (P < .001) and in the subgroups of older children (P < .001) and adolescents (P < .001). End-interval time, the time measured from administration of neuromuscular blockade (NMB) reversal agent to time out of the operating room, was significantly shorter in sugammadex-treated groups in the overall cohort (mean difference, 2.8; 95% CI, 1.85-3.77; P < .001) and all age groups except for first year (31 days through 12 months). This observation was most pronounced in the neonatal subgroup (mean difference, 11.94 minutes; 95% CI, 4.79-19.1; P < .001). No other adverse events measured were found to be different between treatment groups. CONCLUSIONS: This study provides data supporting the safe and effective use of sugammadex for reversal of neuromuscular blockade throughout the entire range of ages in the pediatric population. Within age groups, sugammadex demonstrates faster completion of operation compared with neostigmine, with the greatest difference observed in the neonatal population.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Neostigmina/uso terapêutico , Bloqueio Neuromuscular , Sugammadex/uso terapêutico , Adolescente , Fatores Etários , Período de Recuperação da Anestesia , Bradicardia/induzido quimicamente , Bradicardia/fisiopatologia , Criança , Pré-Escolar , Inibidores da Colinesterase/efeitos adversos , Data Warehousing , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neostigmina/efeitos adversos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Sugammadex/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
2.
J Stroke Cerebrovasc Dis ; 28(11): 104308, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31416760

RESUMO

Stroke involving some areas of the cerebral hemisphere, such as insula, amygdala, and lateral hypothalamus, may cause changes in autonomic control of cardiac function. A 58-year-old woman presented to the emergency department for acute onset of left facial-brachial-crural hemiparesis and dysarthria. A brain CT scan showed subacute ischemic lesion with hemorrhagic infarction in right insular-rolandic cortex. Over the next few days ECG showed severe bradycardia with elongation of QTc, significative pauses (5 seconds), runs of nonsustained ventricular tachycardia and torsades de pointes. Drug induced and other several possible causes of elongation of QT and bradycardia such as hypokalemia, a history of heart failure, and structural heart disease were ruled out. The case confirms that insular cortex plays a major role in stroke-induced cardiovascular changes.


Assuntos
Córtex Cerebral/irrigação sanguínea , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Síndrome do QT Longo/etiologia , Acidente Vascular Cerebral/complicações , Torsades de Pointes/etiologia , Potenciais de Ação , Bradicardia/etiologia , Bradicardia/fisiopatologia , Estimulação Cardíaca Artificial , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/terapia , Pessoa de Meia-Idade , Marca-Passo Artificial , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Torsades de Pointes/diagnóstico , Torsades de Pointes/fisiopatologia , Torsades de Pointes/terapia , Resultado do Tratamento
3.
Med Hypotheses ; 131: 109296, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443773

RESUMO

BACKGROUND: Among the most common autonomic signs visible in preterm neonates, apnea can represent the first sign of several neurologic and non-neurologic disorders, and seizure is a relatively infrequent cause. Herein authors present a case of neonatal autonomic apnea, discussing the polygraphic video-EEG features of this pathological entity and the differential diagnosis with central apnea and autonomic apnea. CASE REPORT: A female preterm Caucasian infant (29 + 4 weeks' gestational age (GA)), first twin of a twin pregnancy, at birth was intubated and surfactant administration was performed. She was ventilated via invasive ventilation for three days, with subsequent weaning with non-invasive ventilation for other two days, when she stopped requiring any ventilator support. After one week the ventilation weaning, the child presented episodes of cyanosis associated with sudden oxygen desaturation, skin pallor, apnea, and bradycardia. Therefore, the child underwent a continuous video-eeg recording with polygraphic study. The exam showed the presence of apneic episodes with an abrupt and clear start, associated with oxygen desaturation at 70%, with minimal thoracic effort at onset, and then evolving into central apnea. Central apnea lasted about 16 s and presented clear start- and end-points. These episodes were also associated with suppression of the EEG trace in frequency and amplitude, and after about 10 s of central apnea an abrupt decrease of the child's heart rate (more than 50% variation, from 160 bpm to 65 bpm) was recorded. In the suspect of epileptic apneas of autonomic origin, a therapy with oral Levetiracetam, at a starting dose of 10 mg/Kg/day, then increased up to 40 mg/Kg/day, was initiated, and after about 48 h the first administration of the anticonvulsant therapy, no new episodes of cyanosis or electrical apneas were recorded. HYPOTHESIS: Herein the authors suggest to consider the diagnosis of autonomic seizures in those neonates with apneic events associated with EEG suppression. Considering that apnea events are not only present in preterm infants but also in term neonates, it is mandatory to diagnose in this context neonatal seizures for a correct diagnosis and a proper therapeutic choice.


Assuntos
Apneia/diagnóstico , Doenças do Sistema Nervoso Autônomo/diagnóstico , Eletroencefalografia , Hipóxia/etiologia , Doenças do Prematuro/diagnóstico , Anticonvulsivantes/uso terapêutico , Apneia/classificação , Apneia/complicações , Apneia/fisiopatologia , Doenças do Sistema Nervoso Autônomo/complicações , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Bradicardia/etiologia , Bradicardia/fisiopatologia , Cianose , Diagnóstico Diferencial , Doenças em Gêmeos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Levetiracetam/uso terapêutico , Convulsões/diagnóstico , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/etiologia , Apneia do Sono Tipo Central/fisiopatologia , Gravação em Vídeo
4.
Card Electrophysiol Clin ; 11(2): 261-281, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31084850

RESUMO

Sinus node dysfunction or atrioventricular blocks are the causes of bradycardias. Diagnosis and management begin with evaluation of patient's hemodynamic status and diagnosis of bradycardia's cause. This is followed by an in depth evaluation of pathophysiology of the arrhythmia, its severity, and likelihood of progression. Implementing emergent measures depends on the presence of subsidiary pace makers maintaining cardiac output. Many of these decisions are greatly helped by 12 lead electrocardiogram, because its tracings are often diagnostic of the cause of the bradycardia and help to assess its persistence and progression and to evaluate the presence and reliability of subsidiary pacemakers.


Assuntos
Bradicardia , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Eletrocardiografia , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Humanos
5.
Circ Arrhythm Electrophysiol ; 12(6): e007415, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31113233

RESUMO

Background His-bundle pacing (HBP) is a physiological form of pacing. Although high capture thresholds are common, few predictors of low HBP threshold have been determined. We aimed to identify electrophysiological predictors. Methods Fifty-one patients (53% with atrioventricular block) underwent HBP for bradycardia with an intrinsic QRS duration of <120 ms. Attempts to anchor the HBP lead were guided by unipolar His-bundle electrograms (HB EGMs) recorded with an electrophysiology recording system. Patients were followed-up for >6 months. Results In total, 153 attempts at anchoring the HBP lead were made, of which, 45 achieved acceptable HBP thresholds (≤2.5 V at 1 ms). The amplitude of negative deflection in HB EGM and the selective HBP form at fixation were independently associated with achieving an acceptable threshold. A negative amplitude of ≥0.060 mV in HB EGM was determined as the optimal value for identifying the acceptable threshold. This deep negative HB EGM was recorded with an HBP threshold of 1.4±1.3 V (in 34 attempts), significantly lower than that of positive HB EGM without deep negative deflection (2.8±1.3 V, in 31 trials; or >5 V, in 38 trials). The permanent HBP lead remained with deep negative (≥0.060 mV) or positive HB EGMs in 28 and 14 patients, respectively, and with positive or negative HB injury current in 19 and 23 patients, respectively. During follow-up, increased HBP threshold of >1 V was significantly more prevalent in the positive HB EGM group. The HBP thresholds of deep negative HB EGM and HB injury current, but not of the selective HBP group, were significantly lower than the other subgroups during follow-up. Conclusions Deep negative HB EGM at fixation was associated with an excellent short-term HBP threshold, similar to HB injury current. Analysis of unipolar HB EGM postfixation may enable prediction of permanent HBP threshold.


Assuntos
Potenciais de Ação , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/terapia , Bradicardia/diagnóstico , Fascículo Atrioventricular/fisiopatologia , Estimulação Cardíaca Artificial , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Bloqueio Atrioventricular/fisiopatologia , Bradicardia/fisiopatologia , Bradicardia/terapia , Estimulação Cardíaca Artificial/efeitos adversos , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
Arq Bras Cardiol ; 112(4): 410-421, 2019 04.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30994720

RESUMO

BACKGROUND: Considering the potential deleterious effects of right ventricular (RV) pacing, the hypothesis of this study is that isolated left ventricular (LV) pacing through the coronary sinus is safe and may provide better clinical and echocardiographic benefits to patients with bradyarrhythmias and normal ventricular function requiring heart rate correction alone. OBJECTIVE: To assess the safety, efficacy, and effects of LV pacing using an active-fixation coronary sinus lead in comparison with RV pacing, in patients eligible for conventional pacemaker (PM) implantation. METHODS: Randomized, controlled, and single-blinded clinical trial in adult patients submitted to PM implantation due to bradyarrhythmias and systolic ventricular function ≥ 0.40. Randomization (RV vs. LV) occurred before PM implantation. The main results of the study were procedural success, safety, and efficacy. Secondary results were clinical and echocardiographic changes. Chi-squared test, Fisher's exact test and Student's t-test were used, considering a significance level of 5%. RESULTS: From June 2012 to January 2014, 91 patients were included, 36 in the RV Group and 55 in the LV Group. Baseline characteristics of patients in both groups were similar. PM implantation was performed successfully and without any complications in all patients in the RV group. Of the 55 patients initially allocated into the LV group, active-fixation coronary sinus lead implantation was not possible in 20 (36.4%) patients. The most frequent complication was phrenic nerve stimulation, detected in 9 (25.7%) patients in the LV group. During the follow-up period, there were no hospitalizations due to heart failure. Reductions of more than 10% in left ventricular ejection fraction were observed in 23.5% of patients in the RV group and 20.6% of those in the LV group (p = 0.767). Tissue Doppler analysis showed that 91.2% of subjects in the RV group and 68.8% of those in the LV group had interventricular dyssynchrony (p = 0.022). CONCLUSION: The procedural success rate of LV implant was low, and the safety of the procedure was influenced mainly by the high rate of phrenic nerve stimulation in the postoperative period.


Assuntos
Bradicardia/terapia , Estimulação Cardíaca Artificial/métodos , Ventrículos do Coração/fisiopatologia , Marca-Passo Artificial , Adulto , Idoso , Idoso de 80 Anos ou mais , Bradicardia/fisiopatologia , Estimulação Cardíaca Artificial/efeitos adversos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Marca-Passo Artificial/efeitos adversos , Implantação de Prótese/métodos , Reprodutibilidade dos Testes , Método Simples-Cego , Volume Sistólico , Resultado do Tratamento , Adulto Jovem
8.
Rev Med Chil ; 147(1): 47-52, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-30848764

RESUMO

BACKGROUND: Cardiovascular complications can occur in up to 80% of adolescent patients with eating disorders (ED) and account for 30% of their mortality. AIM: To evaluate cardiovascular complications in adolescents with ED and their evolution after refeeding. PATIENTS AND METHODS: In adolescents with ED admitted to treatment, we assessed the nutritional status, weight loss prior to consultation, presence of bradycardia (BC, defined as heart rate < 60 bpm), we performed an electrocardiogram (ECG) and an echocardiography and measured thyroid hormones. RESULTS: We studied 53 women aged 16.4 ± 2.3 years. Fifteen had a diagnosis of Anorexia Nervosa (AN), seven of Bulimia (BN), eight a not otherwise specified ED (ED-NOS), four a Binge Eating Disorder (BED), sixteen an Atypical Anorexia (AAN) and three an Atypical Bulimia (ABN). Thirty four percent were malnourished and 3.8% overweight. The most common cardiac problem was BC in 51%. In eight of 26 patients in whom an echocardiogram was done, it was abnormal. Six had a decreased ventricular mass, three a pericardial effusion and three valvular involvement. There was a significant association between bradycardia and malnutrition, weight loss and low free triiodothyronine levels. BC was significantly more common in patients with AN, but it also occurred in half of the patients with AAN and in one of three patients with other types of ED. At follow up, bradycardia significantly improved with refeeding. CONCLUSIONS: There is an association between all types of ED and bradycardia, as well as anatomical and functional cardiac anomalies.


Assuntos
Bradicardia/etiologia , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Adolescente , Análise de Variância , Índice de Massa Corporal , Bradicardia/fisiopatologia , Criança , Estudos de Coortes , Ecocardiografia , Eletrocardiografia , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Feminino , Humanos , Desnutrição/complicações , Desnutrição/fisiopatologia , Fatores de Risco , Estatísticas não Paramétricas , Perda de Peso/fisiologia , Adulto Jovem
9.
J Int Med Res ; 47(5): 2228-2233, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30832535

RESUMO

Thalidomide is effective in inducing and maintaining clinical remission, as well as mucosal healing, in patients with refractory Crohn's disease (CD). However, long-term use of thalidomide has raised concern because of the high incidence of adverse events. Cardiovascular events induced by thalidomide have been reported in patients with multiple myeloma, amyotrophic lateral sclerosis, and transfusion-dependent refractory anemia. We report here an extremely rare case of sinus bradycardia induced by thalidomide in an adult patient with CD. This patient's heart rate converted back to a normal sinus rhythm after withdrawal of thalidomide, but recurred after restarting of thalidomide. Cardiac toxicity should be closely monitored when using thalidomide in patients with CD.


Assuntos
Bradicardia/induzido quimicamente , Bradicardia/complicações , Seio Coronário/patologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Adulto , Bradicardia/fisiopatologia , Frequência Cardíaca , Humanos , Mucosa Intestinal/patologia , Masculino
10.
Cardiovasc J Afr ; 30(2): 103-107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740613

RESUMO

BACKGROUND: Despite the significant clinical benefits of beta-blockers in heart failure with reduced ejection fraction (HFrEF), prescription for and adherence to these agents is reported to be poor. There are few data on the use and tolerance of beta-blocker therapy in patients with HFrEF in South Africa and it is unknown whether these patients would benefit from further heart rate-lowering therapy. METHODS: Data from all patients with HFrEF attending the heart failure clinic of Charlotte Maxeke Johannesburg Academic Hospital from January 2000 to December 2014 were retrospectively collected. We first determined the rates of beta-blocker intolerance in this population and then categorised the patients according to their most recent dose of beta-blocker (low, moderate or target dose) in order to identify factors associated with beta-blocker intolerance. Lastly, we used the data to identify patients who would be suitable for further treatment with heart rate-lowering therapy. RESULTS: Five hundred patients, with a median follow up of 58.7 months, were identified during the study period. Black South Africans constituted the majority (66.4%) and most patients had HFrEF due to hypertension (32.8%). At the last recorded clinic visit at the end of the study period, 489 patients (97.8%) were taking a beta-blocker with 59.8% prescribed a beta-blocker at target dose. Consistent with previous data, bradycardia was the commonest cause for failing to reach target beta-blocker dose. Only 61 (12%) patients were on no (n = 11) or low (n = 50) dose of beta-blocker at final clinic visit. As per current guidelines, only 10.6% (n = 53) of this cohort of patients would qualify for further treatment with heart rate-lowering therapy. CONCLUSIONS: In a dedicated heart failure clinic in South Africa, beta-blockers were well-tolerated in the treatment of HFrEF. The potential role of specific heart rate-lowering therapy in patients treated adequately with heart failure medication and proper up-titration of beta-blockers is relatively small.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antiarrítmicos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Ivabradina/administração & dosagem , Ambulatório Hospitalar , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Idoso , Antiarrítmicos/efeitos adversos , Bradicardia/induzido quimicamente , Bradicardia/fisiopatologia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Ivabradina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , África do Sul , Resultado do Tratamento
11.
Trials ; 20(1): 139, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30782199

RESUMO

BACKGROUND: The need for cardiopulmonary resuscitation (CPR) is often unexpected, and the infrequent use of CPR in the delivery room (DR) limits the opportunity to perform rigorous clinical studies to determine the best method for delivering chest compression (CC) to newborn infants. The current neonatal resuscitation guidelines recommend using a coordinated 3:1 compression-to-ventilation (C:V) ratio (CC at a rate of 90/min and ventilations at a rate of 30/min). In comparison, providing CC during a sustained inflation (SI) (CC + SI) significantly improved hemodynamics, minute ventilation, and time to return of spontaneous circulation (ROSC) compared to 3:1 C:V ratio in asphyxiated piglets. Similarly, a small pilot trial in newborn infants showed similar results. Until now no study has examined different CC techniques during neonatal resuscitation in asphyxiated newborn infants in the DR. To date, no trial has been performed to directly compare CC + SI and 3:1 C:V ratio in the DR during CPR of asphyxiated newborn infants. METHODS: This is a large, international, multi-center, prospective, unblinded, cluster randomized controlled trial in asphyxiated newborn infants at birth. All term and preterm infants > 28+ 0 by best obstetrical estimate who require CPR at birth due to bradycardia (< 60/min) or asystole are eligible. The primary outcome of this study is to compare the time to ROSC in infants born > 28+ 0 weeks' gestational age with bradycardia (< 60/min) or asystole immediately after birth who receive either CC + SI or 3:1 C:V ratio as the CPR strategy. DISCUSSION: Morbidity and mortality rates are extremely high for newborns requiring CC. We believe the combination of simultaneous CC and SI during CPR has the potential to significantly improve ROSC and survival. In addition, we believe that CC + SI might improve respiratory and hemodynamic parameters and potentially minimize morbidity and mortality in newborn infants. In addition, this will be the first randomized controlled trial to examine CC in the newborn period. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02858583 . Registered on 8 August 2016.


Assuntos
Asfixia Neonatal/terapia , Bradicardia/terapia , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Massagem Cardíaca , Respiração Artificial , Ásia , Asfixia Neonatal/diagnóstico , Asfixia Neonatal/fisiopatologia , Austrália , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Reanimação Cardiopulmonar/efeitos adversos , Europa (Continente) , Idade Gestacional , Parada Cardíaca/diagnóstico , Parada Cardíaca/fisiopatologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Estudos Multicêntricos como Assunto , América do Norte , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
12.
Circulation ; 139(18): 2157-2169, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30764634

RESUMO

BACKGROUND: Bradyarrhythmia is a common clinical manifestation. Although the majority of cases are acquired, genetic analysis of families with bradyarrhythmia has identified a growing number of causative gene mutations. Because the only ultimate treatment for symptomatic bradyarrhythmia has been invasive surgical implantation of a pacemaker, the discovery of novel therapeutic molecular targets is necessary to improve prognosis and quality of life. METHODS: We investigated a family containing 7 individuals with autosomal dominant bradyarrhythmias of sinus node dysfunction, atrial fibrillation with slow ventricular response, and atrioventricular block. To identify the causative mutation, we conducted the family-based whole exome sequencing and genome-wide linkage analysis. We characterized the mutation-related mechanisms based on the pathophysiology in vitro. After generating a transgenic animal model to confirm the human phenotypes of bradyarrhythmia, we also evaluated the efficacy of a newly identified molecular-targeted compound to upregulate heart rate in bradyarrhythmias by using the animal model. RESULTS: We identified one heterozygous mutation, KCNJ3 c.247A>C, p.N83H, as a novel cause of hereditary bradyarrhythmias in this family. KCNJ3 encodes the inwardly rectifying potassium channel Kir3.1, which combines with Kir3.4 (encoded by KCNJ5) to form the acetylcholine-activated potassium channel ( IKACh channel) with specific expression in the atrium. An additional study using a genome cohort of 2185 patients with sporadic atrial fibrillation revealed another 5 rare mutations in KCNJ3 and KCNJ5, suggesting the relevance of both genes to these arrhythmias. Cellular electrophysiological studies revealed that the KCNJ3 p.N83H mutation caused a gain of IKACh channel function by increasing the basal current, even in the absence of m2 muscarinic receptor stimulation. We generated transgenic zebrafish expressing mutant human KCNJ3 in the atrium specifically. It is interesting to note that the selective IKACh channel blocker NIP-151 repressed the increased current and improved bradyarrhythmia phenotypes in the mutant zebrafish. CONCLUSIONS: The IKACh channel is associated with the pathophysiology of bradyarrhythmia and atrial fibrillation, and the mutant IKACh channel ( KCNJ3 p.N83H) can be effectively inhibited by NIP-151, a selective IKACh channel blocker. Thus, the IKACh channel might be considered to be a suitable pharmacological target for patients who have bradyarrhythmia with a gain-of-function mutation in the IKACh channel.


Assuntos
Fibrilação Atrial , Bloqueio Atrioventricular , Bradicardia , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G , Doenças Genéticas Inatas , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Animais , Animais Geneticamente Modificados , Fibrilação Atrial/genética , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Bloqueio Atrioventricular/genética , Bloqueio Atrioventricular/metabolismo , Bloqueio Atrioventricular/patologia , Bloqueio Atrioventricular/fisiopatologia , Benzopiranos/farmacologia , Bradicardia/genética , Bradicardia/metabolismo , Bradicardia/patologia , Bradicardia/fisiopatologia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/antagonistas & inibidores , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/metabolismo , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/metabolismo , Doenças Genéticas Inatas/patologia , Doenças Genéticas Inatas/fisiopatologia , Humanos , Masculino , Xenopus laevis , Peixe-Zebra
13.
Eur J Pharmacol ; 849: 154-159, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30716310

RESUMO

Previously, we showed that the synthetic nitroderivative trans-4-methyl-ß-nitrostyrene (T4MeN) induced vasorelaxant effects in rat isolated aortic rings. Here, we investigated the mechanisms underlying the cardiovascular effects of T4MeN in normotensive rats. In pentobarbital-anesthetized rats, intravenous (i.v.) injection of T4MeN (0.03-0.5 mg/kg) induced a rapid (onset time of 1-2 s) and dose-dependent bradycardia and hypotension. These cardiovascular responses to T4MeN were abolished by bilateral cervical vagotomy or selective blockade of neural conduction of vagal C-fiber afferents by perineural treatment of both cervical vagus nerves with capsaicin. Hypotension and bradycardia were also recorded when T4MeN was directly injected in the right, but not into the left ventricle. Furthermore, they were significantly reduced by i.v. pretreatment with capsazepine but remained unaltered by ondansetron or suramin. In conscious rats, the dose-dependent hypotension and bradycardia evoked by T4MeN were abolished by i.v. methylatropine pretreatment. In conclusion, bradycardiac and depressor responses induced by T4MeN has a vago-vagal reflex origin resulting from the vagal pulmonary afferents stimulation. The transduction mechanism seems to involve the activation of vanilloid TRPV1, but not purinergic (P2X) or 5-HT3 receptors located on vagal pulmonary sensory nerves.


Assuntos
Bradicardia/induzido quimicamente , Pulmão/inervação , Fibras Nervosas Amielínicas/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Estirenos/farmacologia , Canais de Cátion TRPV/metabolismo , Nervo Vago/efeitos dos fármacos , Animais , Bradicardia/metabolismo , Bradicardia/fisiopatologia , Masculino , Fibras Nervosas Amielínicas/metabolismo , Fibras Nervosas Amielínicas/fisiologia , Ratos , Ratos Wistar
14.
J Pak Med Assoc ; 69(2): 264-266, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30804598

RESUMO

Persistent left superior vena cava (PLSVC) is one of the commonest venous anomalies of thoracic venous system. These cases usually have normal right sided superior vena cava (SVC). Patients with PLSVC are often asymptomatic hence, it is diagnosed as an incidental finding during procedures like central venous line placement or pacemaker implantation. We report here a case that was taken to catheterization laboratory for pacemaker implantation. Due to PLSVC, we struggled to advance pacing lead into right ventricular apex. We thought of right subclavian vein access but contrast medium injection revealed absent right sided SVC. So procedure was abandoned and finally epicardial placement of the pacing lead was done through subxiphoid laparotomy incision next morning. This case report highlights a rare variant of PLSVC with absent right sided SVC in structurally normal heart and emphasizes the need of pre-procedure assessment of venous anatomy.


Assuntos
Bradicardia/complicações , Cateterismo Venoso Central , Marca-Passo Artificial , Implantação de Prótese , Malformações Vasculares/diagnóstico , Veia Cava Superior , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Bradicardia/cirurgia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Humanos , Achados Incidentais , Cuidados Intraoperatórios/métodos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/efeitos adversos , Implantação de Prótese/métodos , Resultado do Tratamento , Veia Cava Superior/anormalidades , Veia Cava Superior/diagnóstico por imagem
15.
Phys Sportsmed ; 47(3): 249-252, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30640577

RESUMO

It is established that an intensive training results in a lower average resting heart rate. Management of bradycardia in an athlete can be difficult given the underlying mechanisms are not clearly understood. The authors reviewed the different mechanisms described in the literature, including recent advances in physiology regarding remodeling of ion channels, which may partially explain bradycardia in athletes. Sinus bradycardia amongst athletes, especially endurance focused athletes, is common but difficult to apprehend. The underlying mechanisms are observably of multifactorial origin and likely incompletely elucidated by the current body of knowledge.


Assuntos
Atletas , Bradicardia/etiologia , Bradicardia/fisiopatologia , Resistência Física/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
16.
Pacing Clin Electrophysiol ; 42(3): 381-387, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30687931

RESUMO

INTRODUCTION: The MARVEL study demonstrated at a single time point that accelerometer (ACC)-based atrial sensing improves atrioventricular (AV) synchrony (AVS) in patients with AV block and a Micra pacemaker (Medtronic, Minneapolis, MN, USA). The purpose of the MARVEL Evolve substudy was to assess the performance over time. METHODS: This prospective single-center study compared AVS and ACC signals at two visits ≥6 months apart. Custom software was temporarily downloaded into the Micra at each visit and AVS was measured during 30 min at rest. RESULTS: Nine patients from the MARVEL study were enrolled. The mean (±standard deviation) age was 82.3 ± 6.0 years old, 67% were male, and a Micra was implanted for 6.0 ± 6.4 months. High-degree AV block was present in four patients, whereas five with predominantly intrinsic conduction required intermittent pacing for bradycardia. The mean interval between visits was 7.1 ± 0.6 months. Seven patients had normal sinus node function at both visits and were included in a paired analysis. Both ACC signal amplitude (visit 2-visit 1 = 1.4 mG; 95% confidence interval [CI] [-25.8 to 28.4 mG]; P = 0.933) and AVS (visit 1: 90.8%, 95% CI [72.4, 97.4] and visit 2: 91.4%, 95% CI [63.8, 98.5]; P = 0.740) remained stable. Three patients had spontaneous atrial tachycardia. During atrial fibrillation, no atrial contraction was detected or tracked. During atrial flutter, intermittent tracking resulted in a ventricular rate of 60 ± 8 beats per minute (bpm); there was no ventricular pacing >100 bpm. CONCLUSION: ACC signals amplitude and performance of AVS pacing were stable over time. During atrial arrhythmias, the AV synchronous pacing mode behaved safely.


Assuntos
Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/terapia , Bradicardia/fisiopatologia , Bradicardia/terapia , Estimulação Cardíaca Artificial/métodos , Marca-Passo Artificial , Acelerometria , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Humanos , Masculino , Estudos Prospectivos
17.
Korean J Anesthesiol ; 72(2): 164-168, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30481949

RESUMO

BACKGROUND: Sedation by dexmedetomidine, like natural sleep, often causes bradycardia. We explored the nature of heart rate (HR) changes as they occur during natural sleep versus those occurring during dexmedetomidine sedation. METHODS: The present study included 30 patients who were scheduled to undergo elective surgery with spinal anesthesia. To assess HR and sedation, a pulse oximeter and bispectral index (BIS) monitor were attached to the patient in the ward and the operating room. After measuring HR and BIS at baseline, as the patients slept and once their BIS was below 70, HR and BIS were measured at 5-minute intervals during sleep. Baseline HR and BIS were also recorded before spinal anesthesia measured at 5-minute intervals after dexmedetomidine injection. RESULTS: During natural sleep, HR changes ranged from 2 to 19 beats/min (13.4 ± 4.4 beats/min), while in dexmedetomidine sedation, HR ranged from 9 to 40 beats/min (25.4 ± 8.5 beats/min). Decrease in HR was significantly correlated between natural sleep and dexmedetomidine sedation (R2 = 0.41, P < 0.001). The lowest HR was reached in 66 min during natural sleep (59 beats/min) and in 13 min with dexmedetomidine sedation (55 beats/min). The time to reach minimum HR was significantly different (P < 0.001), but there was no difference in the lowest HR obtained (P = 0.09). CONCLUSIONS: There was a correlation between the change in HR during natural sleep and dexmedetomidine sedation. The bradycardia that occurs when using dexmedetomidine may be a normal physiologic change, that can be monitored rather than corrected.


Assuntos
Raquianestesia/métodos , Dexmedetomidina/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Sono/efeitos dos fármacos , Adulto , Raquianestesia/efeitos adversos , Bradicardia/induzido quimicamente , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Monitores de Consciência , Dexmedetomidina/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sono/fisiologia
18.
Heart Vessels ; 34(4): 711-715, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30341630

RESUMO

Resting bradycardia is an important symptom for early diagnosis of anorexia nervosa (AN) during weight loss, and it improves with body-weight recovery. However, chronotropic incompetence (CI) in exercise is observed in some patients with AN despite amelioration of resting bradycardia in the recovery phase. We examined the relationship between CI in exercise and other parameters in patients with AN during the recovery phase. Ninety-two girls with AN (aged 13-20 years, median 15 years) performed cardiopulmonary exercise tolerance tests with a bicycle ergometer in the post-treatment recovery phase. Subjects with a peak-heart rate (HR) of < 160 beats/min (bpm) on subjective maximum loading were assigned to the CI+ group (n = 7), and those with a peak-HR of ≥ 160 bpm were assigned to the CI- group (n = 85). The peak-oxygen uptake (VO2) of both groups was below the normal range. Although there was no difference in peak-VO2 between these groups, both the resting-HR and ΔHR (peak-HR - resting-HR) were significantly lower in the CI+ group than in the CI- group (82 ± 8 vs. 93 ± 16 bpm, respectively; 72 ± 14 vs. 89 ± 13 bpm, respectively), suggesting lower exercise tolerance in patients with CI during the recovery phase of AN. Interestingly, the ΔVO2/ΔHR value was higher in the CI+ group than in the CI- group (0.31 ± 0.13 vs. 0.26 ± 0.06, respectively), suggesting excessive stroke volume for maintaining the cardiac output in patients with CI during their recovery phase. These data suggest that CI could be an index of insufficient recovery of AN and utilized for ideal exercise treatments of patients with AN during the recovery phase.


Assuntos
Anorexia Nervosa/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Bradicardia/fisiopatologia , Ritmo Circadiano/fisiologia , Terapia por Exercício/métodos , Tolerância ao Exercício/fisiologia , Frequência Cardíaca/fisiologia , Adolescente , Adulto , Anorexia Nervosa/complicações , Anorexia Nervosa/reabilitação , Peso Corporal , Bradicardia/etiologia , Bradicardia/reabilitação , Criança , Eletrocardiografia , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Volume Sistólico/fisiologia , Adulto Jovem
19.
Int Heart J ; 60(1): 185-188, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30464125

RESUMO

Patients presenting with aborted cardiac arrest who display early repolarization generally are diagnosed with early repolarization syndrome. Therapeutic hypothermia is a standard strategy to improve neurological outcome in comatose patients after cardiac arrest. We present here a patient in whom therapeutic hypothermia exacerbated the J-wave amplitude and morphology, which resulted in episodes of refractory ventricular fibrillation.


Assuntos
Frequência Cardíaca/fisiologia , Hipotermia Induzida/métodos , Fibrilação Ventricular/diagnóstico , Adulto , Bradicardia/fisiopatologia , Reanimação Cardiopulmonar/métodos , Ablação por Cateter/métodos , Desfibriladores , Desfibriladores Implantáveis , Parada Cardíaca/terapia , Humanos , Masculino , Sobreviventes , Resultado do Tratamento , Fibrilação Ventricular/terapia
20.
Arch Dis Child Fetal Neonatal Ed ; 104(1): F98-F101, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29778994

RESUMO

BACKGROUND: The Neonatal Resuscitation Program (NRP) states that if adequate positive pressure ventilation (PPV) was given for a low heart rate (HR), the infant's HR should increase within the first 15 s of PPV. OBJECTIVE: To assess changes in HR in piglets with asphyxia-induced bradycardia. METHODS: Term newborn piglets (n=30) were anaesthetised, intubated, instrumented and exposed to 50 min normocapnic hypoxia followed by asphyxia. Asphyxia was achieved by clamping the tube until severe bradycardia (defined as HR at <25% of baseline). This was followed by 30 s adequate PPV and chest compression thereafter. Changes in HR during the 30 s of PPV were assessed and divided into four epochs (0-10 s, 5-15 s, 10-20 s and 20-30 s, respectively). RESULTS: Increase in HR >100/min was observed in 6/30 (20%) after 30 s of PPV. Within the epochs 0-10 s, 5-15 s or 10-20 s no piglet had an increase in HR >100/min. Additional 10/30 (33%) had a >10% increase in HR. CONCLUSION: In contrast to NRP recommendation, adequate PPV does not increase HR within 15 s after ventilation in piglets with asphyxia-induced bradycardia.


Assuntos
Bradicardia/fisiopatologia , Bradicardia/terapia , Reanimação Cardiopulmonar/métodos , Frequência Cardíaca/fisiologia , Respiração com Pressão Positiva/métodos , Animais , Animais Recém-Nascidos , Asfixia/complicações , Asfixia/fisiopatologia , Bradicardia/etiologia , Reanimação Cardiopulmonar/efeitos adversos , Modelos Animais de Doenças , Eletrocardiografia , Respiração com Pressão Positiva/efeitos adversos , Suínos
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