Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.635
Filtrar
1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(11): 990-995, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33210593

RESUMO

Objective To investigate the role of butorphanol in alleviating ischemic arrhythmias and its regulatory effects on the microRNA-1-3p/connexin 43 (miR-1-3p/Cx43) pathway. Methods SD rats were divided into the following groups: control group (the treatment was the same as that of modeling, but no coronary artery ligation was performed), butorphanol group (rats were injected 50 µg/kg butorphanol into the femoral vein after the needle has penetrated the myocardial surface), inhibitor group (5 days before the experiment, 80 mg/kg miR-1-3p inhibitor was administered via the tail vein, and the other treatment were the same as the control group); model group (ligation method was used to prepare rat ischemic arrhythmia models), butorphanol pretreatment group (50 µg/kg butorphanol was given at 5 minutes before ischemic treatment, and the other treatment were the same as the model group), inhibitor pretreatment group (5 days before the experiment, 80 mg/kg miR-1-3p inhibitor was administered via the tail vein, and the other treatment were the same as the model group). According to the electrocardiogram results, the ventricular arrhythmia score in each group was evaluated. Targetscan database was used to predict the upstream miRNAs of Cx43. Real-time quantitative PCR (qRT-PCR) was used to detect the expression of miR-1-3p and Cx43 mRNA. Western blotting was performed to detect the expression of Cx43 in myocardial tissue. The binding of miR-1-3p and Cx43 mRNA was verified by double luciferase report experiment. Results Butorphanol significantly reduced the frequency of ventricular premature beat, ventricular arrhythmia score, duration of ventricular fibrillation and duration of ventricular tachycardia in ischemic arrhythmia rats, and significantly increased the expression of Cx43 protein in myocardial tissue. Subsequently, two binding sites of miR-1-3p were found in the 3' untranslated region of Cx43 mRNA. Additionally, butorphanol significantly reduced the level of miR-1-3p in myocardium. Inhibition of miR-1-3p significantly decreased the total score of ventricular arrhythmia in the rats with ischemic arrhythmia, and significantly increased the expression of Cx43 mRNA and protein. Conclusion Butorphanol can improve ischemic arrhythmia by up-regulating the expression of Cx43 mediated by miR-1-3p.


Assuntos
Arritmias Cardíacas , Butorfanol , Conexina 43 , MicroRNAs , Regulação para Cima , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/genética , Butorfanol/farmacologia , Conexina 43/genética , MicroRNAs/genética , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
2.
Orv Hetil ; 161(46): 1953-1958, 2020 11 15.
Artigo em Húngaro | MEDLINE | ID: mdl-33190126

RESUMO

Összefoglaló. Bevezetés: Az inadekvát, aránytalan sinuscsomó-tachycardia a szív nomotop ingerképzési zavarával járó, nem ritka klinikai szindróma. A szívritmuszavar-entitást a nem paroxysmalis, magas nyugalmi sinusfrekvencia, a fizikai/pszichés stresszre adott aránytalan sinustachycardia, valamint foként palpitációs panaszok jellemzik. Célkituzés: Az aránytalan sinuscsomó-tachycardiás betegeink gyógyszeres kezelésével szerzett tapasztalataink ismertetése. Módszerek: 2008 és 2018 között 104 beteget (92 no, 12 férfi; átlagéletkor 31 ± 10 év) kezeltünk ezzel a szívritmuszavarral. A betegek kivizsgálásuk után 12 elvezetéses EKG-, terheléses EKG-, valamint 24 órás Holter-monitoros EKG-megfigyeléseken vettek részt a gyógyszeres kezelés elott és után (bizoprolol: 2 × 5 mg/nap; ivabradin: 2 × 5 mg/nap). Az életminoség változását a European Heart Rhythm Association (EHRA) tüneti skálája szerint állapítottuk meg. Eredmények: Mindkét gyógyszer jelentosen csökkentette a nyugalmi sinusfrekvenciát (kontroll: 102 ± 10/min; bizoprolol: 78 ± 6/min; ivabradin: 74 ± 8/min, mindketto: p<0,0001). A gyógyszeres kezelés nélküli, 24 órás Holter-monitoros EKG-felvételek során mért szívfrekvenciák (minimum-maximum [átlag] sinusfrekvencia/min) a kontrollértékekrol (58 ± 8-159 ± 14 [94 ± 6]/min) mindkét gyógyszerre egyaránt szignifikánsan csökkentek (bizoprolol: 53 ± 7-132 ± 13 [77 ± 9]/min [mindhárom: p<0,0001]; ivabradin 51 ± 6-134 ± 18 [77 ± 8]/min [mindhárom: p<0,0001]). A terheléses EKG-vizsgálatok elott (kontroll: 99 ± 13/min; bizoprolol 81 ± 11/min [p<0,0001]; ivabradin: 84 ± 10/min [p<0,0001]) és a terhelés csúcspontján mért sinusfrekvenciák (kontroll: 164 ± 15/min; bizoprolol: 140 ± 16/min [p<0,0001]; ivabradin: 142 ± 14/min [p<0,0001]) is jelentosen mérséklodtek. Az azonos dózisban adott két gyógyszer szívfrekvencia-csökkento hatásai között számottevo különbséget nem tapasztaltunk. Az életminoséget tükrözo EHRA tüneti skálán (kontroll: 2,3 ± 0,7) mind a bizoprolol (1,4 ± 1,4; p<0,0001), mind az ivabradin (1,1 ± 0,2; p<0,0001) egyformán csökkentette a betegek tüneteit, panaszait. Számottevo cardiovascularis mellékhatás egyik betegcsoportban sem jelentkezett. Következtetések: Vizsgálati eredményeink alapján megállapítható, hogy az aránytalan sinuscsomó-tachycardiás betegek gyógyszeres kezelésére: (1) a kardiospecifikus adrenerg béta-blokkoló bizoprolol és az If-csatorna-gátló ivabradin egyaránt hatékonynak és biztonságosnak bizonyult; (2) az azonos adagban adott két gyógyszer hatékonysága között számottevo különbség nem volt; (3) a gyógyszeres kezelés nemcsak a sinusfrekvenciát csökkentette, hanem a betegek panaszait, tüneteit is mérsékelte. Orv Hetil. 2020; 161(46): 1953-1958. INTRODUCTION: The inadequate, inappropriate sinus-node tachycardia is not a rare clinical syndrome, defined as a disturbance of the nomotopic impulse formation of the heart. This cardiac arrhythmic entity is characterized by a non-paroxismal, increased sinus rate at rest, and/or inadequate response to physical and/or emotional stress and palpitations. OBJECTIVE: The aim of this study was to describe our experiences with pharmacological therapy of patients with inappropriate sinus tachycardia syndrome. METHODS: Between 2008 and 2018, 104 patients (92 women, 12 men, mean age: 31 ± 10 years) were treated with this cardiac arrhythmia entity. All patients underwent 12-lead ECG, 24-hour Holter-ECG monitoring and standard bicycle dynamic exercise tests before and after drug treatment (bisoprolol: 5 mg bid; ivabradine: 5 mg bid). Changes in the quality of life were estimated by using the European Heart Rhythm Association (EHRA) score. RESULTS: Both drugs decreased significantly the resting heart rate (control: 102 ± 10/min; bisoprolol 78 ± 6/min (p<0.0001), ivabradine: 74 ± 8/min (p<0.0001). The results of the parameters of the 24-hour Holter ECG recordings (expressed as minimal-maximal [average] heart rate/min) with drug therapy showed a significant decrease from control values in all three parameters: control 58 ± 8-159 ± 14 (94 ± 6)/min; bisoprolol 53 ± 7-132 ±13 (77 ± 9)/min (all three: p<0.0001); ivabradine: 51 ± 6-134 ± 18 (77 ± 8)/min (all three: p<0.0001). The sinus rate reduced significantly both before the bicycle dynamic exercise tests (control: 99 ± 13/min; bisoprolol: 81 ± 11/min [p<0.0001]; ivabradine: 84 ± 10/min [p<0.0001]) and at the peaks of the exercise test (control: 164 ± 15/min; bisoprolol: 140 ± 16/min [p<0.0001]; ivabradine 142 ± 14/min [p<0.0001]). The heart rate reducing effects of the two drugs did not differ significantly. The EHRA quality of life score was equally improved by the two drugs (control: 2.3 ± 0.7; bisoprolol: 1.4 ± 1.4 [p<0.0001]; ivabradine: 1.1 ± 0.2 [p<0.0001]). No cardiovascular side effects were observed while taking bisoprolol or ivabradine. CONCLUSIONS: Based on our clinical results, it can be pointed out that in the drug therapy of patients with inappropriate sinus node tachycardia: (1) bisoprolol (5 mg bid) and ivabradine (5 mg bid) proved to be equally effective and safe; (2) the heart rate reducing effect of the two drugs - given in the same dosage - did not differ considerably; (3) the pharmacological therapy significantly decreased not only the sinus frequency, but also reduced the symptoms of the patients. Orv Hetil. 2020; 161(46): 1953-1958.


Assuntos
Qualidade de Vida , Taquicardia Sinusal , Adulto , Arritmias Cardíacas/tratamento farmacológico , Eletrocardiografia , Eletrocardiografia Ambulatorial , Feminino , Frequência Cardíaca , Humanos , Masculino , Taquicardia Sinusal/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
4.
Sci Rep ; 10(1): 15284, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943714

RESUMO

Acute myocardial ischaemia and reperfusion (I-R) are major causes of ventricular arrhythmias in patients with a history of coronary artery disease. Ursodeoxycholic acid (UDCA) has previously been shown to be antiarrhythmic in fetal hearts. This study was performed to investigate if UDCA protects against ischaemia-induced and reperfusion-induced arrhythmias in the adult myocardium, and compares the effect of acute (perfusion only) versus prolonged (2 weeks pre-treatment plus perfusion) UDCA administration. Langendorff-perfused adult Sprague-Dawley rat hearts were subjected to acute regional ischaemia by ligation of the left anterior descending artery (10 min), followed by reperfusion (2 min), and arrhythmia incidence quantified. Prolonged UDCA administration reduced the incidence of acute ischaemia-induced arrhythmias (p = 0.028), with a reduction in number of ventricular ectopic beats during the ischaemic phase compared with acute treatment (10 ± 3 vs 58 ± 15, p = 0.036). No antiarrhythmic effect was observed in the acute UDCA administration group. Neither acute nor prolonged UDCA treatment altered the incidence of reperfusion arrhythmias. The antiarrhythmic effect of UDCA may be partially mediated by an increase in cardiac wavelength, due to the attenuation of conduction velocity slowing (p = 0.03), and the preservation of Connexin43 phosphorylation during acute ischaemia (p = 0.0027). The potential antiarrhythmic effects of prolonged UDCA administration merit further investigation.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Coração/efeitos dos fármacos , Isquemia Miocárdica/complicações , Ácido Ursodesoxicólico/administração & dosagem , Animais , Antiarrítmicos/administração & dosagem , Vasos Coronários/efeitos dos fármacos , Masculino , Reperfusão Miocárdica/métodos , Traumatismo por Reperfusão Miocárdica/complicações , Miocárdio/patologia , Perfusão/métodos , Ratos , Ratos Sprague-Dawley
5.
Am J Cardiovasc Drugs ; 20(5): 413-418, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32737841

RESUMO

Amiodarone, one of the most widely prescribed antiarrhythmic drugs to treat both ventricular and supraventricular arrhythmias, has been identified as a candidate drug for use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present the rationale of using amiodarone in the COVID-19 scenario, as well as whether or not amiodarone administration represents a potential strategy to prevent SARS-CoV-2 infection, rather than simply used to treat patients already symptomatic and/or with severe coronavirus disease 2019 (COVID-19), based on current evidence.


Assuntos
Amiodarona/farmacologia , Arritmias Cardíacas , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Antiarrítmicos/farmacologia , Antivirais/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/virologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/prevenção & controle , Medição de Risco , Resultado do Tratamento , Internalização do Vírus/efeitos dos fármacos
6.
Am J Cardiol ; 133: 77-80, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32843146

RESUMO

Bretylium, with an extensive pharmacologic and medicinal history, was approved by the United States Food and Drug Administration in 1986 for "short-term prevention and treatment of ventricular fibrillation (VF) and treatment of life-threatening ventricular arrhythmias and ventricular tachycardia (VT) unresponsive to adequate doses of a first-line antiarrhythmic agent, such as lidocaine." The NDA sponsor withdrew bretylium from the market in 2011, largely due to unavailability of raw materials required for its production; prior to this, bretylium was removed from the 2000 ACLS Guidelines algorithm for VF/pulseless VT given the challenges obtaining raw materials for drug manufacture. Recently, bretylium has been reintroduced into the US market by a generic pharmaceutical company with the same indications as before. This article provides a history of the salient trials evaluating the efficacy and safety of bretylium and looks to the future as bretylium finds its place in the modern day management of ventricular arrhythmia.


Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Compostos de Bretílio/farmacologia , Recall e Retirada de Produto , Humanos
7.
Ann Hematol ; 99(10): 2289-2294, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32737633

RESUMO

Iron overload-induced cardiomyopathy is the leading cause of death in patients with transfusion-dependent thalassemia (TDT). The mortality is extremely high in these patients with severe cardiac complications, and how to rescue them remains a challenge. It is reasonable to use combined chelation with deferiprone (L1) and deferoxamine (DFO) because of their shuttle and synergistic effects on iron chelation. Here, seven consecutive patients with TDT who had severe cardiac complications between 2002 and 2019 and received combined chelation therapy with oral high-dose L1 (100 mg/kg/day) and continuous 24-h DFO infusion (50 mg/kg/day) in our hospital were reported. Survival for eight consecutive patients receiving DFO monotherapy for their severe cardiac complications between 1984 and 2001 was compared. We found that combined chelation therapy with high-dose L1 and DFO was efficient to improve survival and cardiac function in patients with TDT presenting severe cardiac complications. Reversal of arrhythmia to sinus rhythm was noted in all patients. Their 1-month follow-up left ventricular ejection fraction increased significantly (P < 0.001). There were no deaths, and all patients were discharged from hospital with good quality of life. In contrast, all the eight patients receiving DFO monotherapy died (P < 0.001). Accordingly, combined chelation therapy with high-dose L1 and DFO should be considered in patients with TDT presenting cardiac complications.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Terapia por Quelação/métodos , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Talassemia/terapia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Transfusão de Sangue , Deferiprona/administração & dosagem , Desferroxamina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/etiologia , Masculino , Qualidade de Vida , Estudos Retrospectivos , Talassemia/complicações , Reação Transfusional , Resultado do Tratamento , Função Ventricular Esquerda
8.
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
9.
Arq Bras Cardiol ; 114(4): 732-735, 2020 04.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32491007

RESUMO

Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells.


Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas , Síndrome do QT Longo , Ranolazina/uso terapêutico , Potenciais de Ação , Arritmias Cardíacas/tratamento farmacológico , Doença do Sistema de Condução Cardíaco , Humanos
10.
Am Surg ; 86(4): 354-361, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32391760

RESUMO

In recent years, the incidence of blunt cardiac injury (BCI) has increased rapidly and is an important cause of death in trauma patients. This study aimed to explore early diagnosis and therapy to increase survival. All patients with BCI during the past 15 years were analyzed retrospectively regarding the mechanism of injury, diagnostic and therapeutic methods, and outcome. The patients were divided into two groups according to the needs of their condition-nonoperative (Group A) and operative (Group B). Comparisons of the groups were performed. A total of 348 patients with BCI accounted for 18.3 per cent of 1903 patients with blunt thoracic injury. The main cause of injury was traffic accidents, with an incidence of 48.3 per cent. In Group A (n = 305), most patients sustained myocardial contusion, and the mortality was 6.9 per cent. In Group B (n = 43), including those with cardiac rupture and pericardial hernia, the mortality was 32.6 per cent. Comparisons of the groups regarding the shock rate and mortality were significant (P < 0.01). Deaths directly resulting from BCI in Group B were greater than those in Group A (P < 0.05). In all 348 patients, the mortality rate was 10.1 per cent. When facing a patient with blunt thoracic injury, a high index of suspicion for BCI must be maintained. To manage myocardial contusion, it is necessary to protect the heart, alleviate edema of the myocardium, and control arrhythmia with drugs. To deal with those requiring operation, early recognition and expeditious thoracotomy are essential.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Traumatismos Cardíacos , Ferimentos não Penetrantes , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/etiologia , Ecocardiografia , Eletrocardiografia , Feminino , Coração/diagnóstico por imagem , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/mortalidade , Traumatismos Cardíacos/terapia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos Torácicos/complicações , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/mortalidade , Ferimentos não Penetrantes/terapia , Adulto Jovem
11.
Chem Commun (Camb) ; 56(41): 5480-5483, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32342077

RESUMO

Control of biological function by the use of photoremovable protecting groups (PPGs) is a gateway towards many new medical developments. Herein, we report the synthesis and application of efficient and biocompatible BODIPY-based photoprotecting groups for amines, which are cleavable with red light in the phototherapeutic window region (λ > 650 nm). We use the most promising PPG for the protection of dopamine and apply it to control the beating frequency of human cardiomyocytes.


Assuntos
Aminas/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Compostos de Boro/química , Luz , Fototerapia , Aminas/química , Humanos , Estrutura Molecular , Miócitos Cardíacos/efeitos dos fármacos , Processos Fotoquímicos
12.
Dtsch Med Wochenschr ; 145(8): 526-535, 2020 04.
Artigo em Alemão | MEDLINE | ID: mdl-32294778

RESUMO

The use of medical antiarrhythmic therapy apart from beta-blockers has been steadily decreasing in the recent past. This can partly be attributed to technological progress that has rendered the ablation of complex cardiac arrhythmias like atrial fibrillation, focal atrial tachycardias and ventricular arrhythmias feasible and efficacious. Furthermore, an awareness regarding pro-arrhythmic and toxic side-effects of antiarrhythmic medication has evolved. Nevertheless, medical antiarrhythmic therapy still plays a fundamental role in acute therapy of arrythmias as well as certain indications for long-term therapy. This review comprehensively summarizes the current role of medical antiarrhythmic therapy in daily clinical practice focusing on mechanisms and therapies of the most common cardiac arrythmias.


Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Arritmias Cardíacas/cirurgia , Ablação por Cateter , Coração/efeitos dos fármacos , Coração/fisiologia , Humanos
13.
Sci Rep ; 10(1): 6878, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32327677

RESUMO

Alterations in connexins and specifically in 43 isoform (Cx43) in the heart have been associated with a high incidence of arrhythmogenesis and sudden death in several cardiac diseases. We propose to determine salutary effect of Cx43 mimetic peptide Gap27 in the progression of heart failure. High-output heart failure was induced by volume overload using the arterio-venous fistula model (AV-Shunt) in adult male rats. Four weeks after AV-Shunt surgery, the Cx43 mimetic peptide Gap27 or scrambled peptide, were administered via osmotic minipumps (AV-ShuntGap27 or AV-ShuntScr) for 4 weeks. Cardiac volumes, arrhythmias, function and remodeling were determined at 8 weeks after AV-Shunt surgeries. At 8th week, AV-ShuntGap27 showed a marked decrease in the progression of cardiac deterioration and showed a significant improvement in cardiac functions measured by intraventricular pressure-volume loops. Furthermore, AV-ShuntGap27 showed less cardiac arrhythmogenesis and cardiac hypertrophy index compared to AV-ShuntScr. Gap27 treatment results in no change Cx43 expression in the heart of AV-Shunt rats. Our results strongly suggest that Cx43 play a pivotal role in the progression of cardiac dysfunction and arrhythmogenesis in high-output heart failure; furthermore, support the use of Cx43 mimetic peptide Gap27 as an effective therapeutic tool to reduce the progression of cardiac dysfunction in high-output heart failure.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/fisiopatologia , Conexina 43/química , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Peptídeos/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico por imagem , Derivação Arteriovenosa Cirúrgica , Cardiomegalia/complicações , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/fisiopatologia , Fibrose , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Masculino , Peptídeos/administração & dosagem , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos
14.
Oxid Med Cell Longev ; 2020: 4850697, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273944

RESUMO

Background: Cardiomyopathies remain among the leading causes of death worldwide, despite all efforts and important advances in the development of cardiovascular therapeutics, demonstrating the need for new solutions. Herein, we describe the effects of the redox-active therapeutic Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, AEOL10113, BMX-010 (MnTE-2-PyP5+), on rat heart as an entry to new strategies to circumvent cardiomyopathies. Methods: Wistar rats weighing 250-300 g were used in both in vitro and in vivo experiments, to analyze intracellular Ca2+ dynamics, L-type Ca2+ currents, Ca2+ spark frequency, intracellular reactive oxygen species (ROS) levels, and cardiomyocyte and cardiac contractility, in control and MnTE-2-PyP5+-treated cells, hearts, or animals. Cells and hearts were treated with 20 µM MnTE-2-PyP5+ and animals with 1 mg/kg, i.p. daily. Additionally, we performed electrocardiographic and echocardiographic analysis. Results: Using isolated rat cardiomyocytes, we observed that MnTE-2-PyP5+ reduced intracellular Ca2+ transient amplitude, without altering cell contractility. Whereas MnTE-2-PyP5+ did not alter basal ROS levels, it was efficient in modulating cardiomyocyte redox state under stress conditions; MnTE-2-PyP5+ reduced Ca2+ spark frequency and increased sarcoplasmic reticulum (SR) Ca2+ load. Accordingly, analysis of isolated perfused rat hearts showed that MnTE-2-PyP5+ preserves cardiac function, increases SR Ca2+ load, and reduces arrhythmia index, indicating an antiarrhythmic effect. In vivo experiments showed that MnTE-2-PyP5+ treatment increased Ca2+ transient, preserved cardiac ejection fraction, and reduced arrhythmia index and duration. MnTE-2-PyP5+ was effective both to prevent and to treat cardiac arrhythmias. Conclusion: MnTE-2-PyP5+ prevents and treats cardiac arrhythmias in rats. In contrast to most antiarrhythmic drugs, MnTE-2-PyP5+ preserves cardiac contractile function, arising, thus, as a prospective therapeutic for improvement of cardiac arrhythmia treatment.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Metaloporfirinas/uso terapêutico , Oxirredução/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Wistar
15.
Clin Drug Investig ; 40(4): 343-353, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32144651

RESUMO

BACKGROUND AND OBJECTIVES: The efficacy of direct oral anticoagulants (DOACs) in the management of left ventricular (LV) thrombi remains to be determined, especially in patients with ischemic cardiomyopathy. This retrospective study sought to compare the efficacy of vitamin K antagonists (VKAs) and DOACs in patients with LV thrombi and evaluate the rate of LV thrombus resolution after adjusting anticoagulation. METHODS: This observational retrospective study included patients admitted to our institution for LV thrombus between January 2010 and August 2019. The rate of LV thrombus resolution was compared between VKAs and DOACs. Patients without thrombus resolution with DOAC treatment were switched to VKA agents in order to obtain an international normalized ratio (INR) of 3-4. RESULTS: Between January 2010 and August 2019, 59 consecutive patients with LV thrombi detected by transthoracic echocardiography were included in the study. The mean age was 62 ± 14 years and 16.9% were women. The circumstances of LV thrombus discovery were as follows: acute myocardial infarction or ischemic myocardiopathy (n = 22), stroke (n = 6), chest pain (n = 7), heart failure (n = 11), transthoracic echocardiographic evaluation (n = 11), and ventricular arrhythmias (n = 2). The proportion of patients on DOACs was 28.8% (n = 17), while that of those on VKAs was 71.2% (n = 42). Thrombus resolution was obtained in 70.6% (12/17) of patients on DOACs and in 71.4% (30/42) of those on VKAs (p = 0.9). Patients who failed to respond to DOAC treatment were treated with VKAs, and following this treatment adjustment all LV thrombi were dissolved in the DOAC group (5/5). Five embolic events (8.4% of stroke) occurred before the treatment initiation and six with anticoagulants (2/17 with DOACs [11.8%] and 4/42 with VKAs [9.5%]; p = 0.8). CONCLUSIONS: This retrospective observational study found a similar efficacy between DOAC and VKA agents in patients with LV thrombi (70.6% vs. 71.5%); however, when the thrombus remains, VKAs are still the standard of care as it is possible to control INR levels (3-4) with them.


Assuntos
Anticoagulantes/uso terapêutico , Trombose/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Administração Oral , Adulto , Idoso , Arritmias Cardíacas/tratamento farmacológico , Feminino , Fibrinolíticos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico
17.
Mol Pharmacol ; 97(4): 250-258, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32015008

RESUMO

Phenytoin is a hydantoin derivative that is used clinically for the treatment of epilepsy and has been reported to have antiarrhythmic actions on the heart. In a failing heart, the elevated diastolic Ca2+ leak from the sarcoplasmic reticulum can be normalized by the cardiac ryanodine receptor 2 (RyR2) inhibitor, dantrolene, without inhibiting Ca2+ release during systole or affecting Ca2+ release in normal healthy hearts. Unfortunately, dantrolene is hepatotoxic and unsuitable for chronic long-term administration. Because phenytoin and dantrolene belong to the hydantoin class of compounds, we test the hypothesis that dantrolene and phenytoin have similar inhibitory effects on RyR2 using a single-channel recording of RyR2 activity in artificial lipid bilayers. Phenytoin produced a reversible inhibition of RyR2 channels from sheep and human failing hearts. It followed a hyperbolic dose response with maximal inhibition of ∼50%, Hill coefficient ∼1, and IC50 ranging from 10 to 20 µM. It caused inhibition at diastolic cytoplasmic [Ca2+] but not at Ca2+ levels in the dyadic cleft during systole. Notably, phenytoin inhibits RyR2 from failing human heart but not from healthy heart, indicating that phenytoin may selectively target defective RyR2 channels in humans. We conclude that phenytoin could effectively inhibit RyR2-mediated release of Ca2+ in a manner paralleling that of dantrolene. Moreover, the IC50 of phenytoin in RyR2 is at least threefold lower than for other ion channels and clinically used serum levels, pointing to phenytoin as a more human-safe alternative to dantrolene for therapies against heart failure and cardiac arrythmias. SIGNIFICANCE STATEMENT: We show that phenytoin, a Na channel blocker used clinically for treatment of epilepsy, is a diastolic inhibitor of cardiac calcium release channels [cardiac ryanodine receptor 2 (RyR2)] at doses threefold lower than its current therapeutic levels. Phenytoin inhibits RyR2 from failing human heart and not from healthy heart, indicating that phenytoin may selectively target defective RyR2 channels in humans and pointing to phenytoin as a more human-safe alternative to dantrolene for therapies against heart failure and cardiac arrhythmias.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cardiotônicos/farmacologia , Insuficiência Cardíaca/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Fenitoína/farmacologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/patologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardiotônicos/uso terapêutico , Dantroleno/farmacologia , Dantroleno/uso terapêutico , Relação Dose-Resposta a Droga , Vesículas Extracelulares , Insuficiência Cardíaca/patologia , Humanos , Bicamadas Lipídicas , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenitoína/uso terapêutico , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo , Ovinos
18.
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
19.
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
20.
Circ Res ; 126(8): 947-964, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32091972

RESUMO

RATIONALE: Drug-induced proarrhythmia is so tightly associated with prolongation of the QT interval that QT prolongation is an accepted surrogate marker for arrhythmia. But QT interval is too sensitive a marker and not selective, resulting in many useful drugs eliminated in drug discovery. OBJECTIVE: To predict the impact of a drug from the drug chemistry on the cardiac rhythm. METHODS AND RESULTS: In a new linkage, we connected atomistic scale information to protein, cell, and tissue scales by predicting drug-binding affinities and rates from simulation of ion channel and drug structure interactions and then used these values to model drug effects on the hERG channel. Model components were integrated into predictive models at the cell and tissue scales to expose fundamental arrhythmia vulnerability mechanisms and complex interactions underlying emergent behaviors. Human clinical data were used for model framework validation and showed excellent agreement, demonstrating feasibility of a new approach for cardiotoxicity prediction. CONCLUSIONS: We present a multiscale model framework to predict electrotoxicity in the heart from the atom to the rhythm. Novel mechanistic insights emerged at all scales of the system, from the specific nature of proarrhythmic drug interaction with the hERG channel, to the fundamental cellular and tissue-level arrhythmia mechanisms. Applications of machine learning indicate necessary and sufficient parameters that predict arrhythmia vulnerability. We expect that the model framework may be expanded to make an impact in drug discovery, drug safety screening for a variety of compounds and targets, and in a variety of regulatory processes.


Assuntos
Antiarrítmicos/química , Arritmias Cardíacas/tratamento farmacológico , Cardiotoxinas/química , Simulação por Computador , Descoberta de Drogas/métodos , Canal de Potássio ERG1/química , Antiarrítmicos/metabolismo , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/metabolismo , Cardiotoxicidade/metabolismo , Cardiotoxicidade/prevenção & controle , Cardiotoxinas/efeitos adversos , Cardiotoxinas/metabolismo , Descoberta de Drogas/tendências , Canal de Potássio ERG1/metabolismo , Feminino , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/metabolismo , Aprendizado de Máquina , Masculino , Moxifloxacina/química , Moxifloxacina/metabolismo , Moxifloxacina/uso terapêutico , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Fenetilaminas/química , Fenetilaminas/metabolismo , Fenetilaminas/uso terapêutico , Estrutura Secundária de Proteína , Sulfonamidas/química , Sulfonamidas/metabolismo , Sulfonamidas/uso terapêutico , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/metabolismo , Inibidores da Topoisomerase II/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA