RESUMEN
This study explored the intrinsic vasorelaxant and inotropic effects of the mixed potassium and sodium channel blocker atrial antiarrhythmic vernakalant and the class IC antiarrhythmic agent flecainide in human isolated subcutaneous resistance artery and in ventricular trabecular muscle preparations. At test concentrations encompassing free plasma concentrations associated with clinical efficacy for conversion of atrial fibrillation, vernakalant (1-10 µM) displayed no significant direct effects on human resistance artery tone or ventricular contractility. In contrast, tested at equimolar concentrations, flecainide significantly reduced peak isometric contractile force (10 µM) and maximal rates of force development and decline (3 and 10 µM) in the human ventricular muscle preparation while displaying no significant effect on human resistance artery tone. The lack of effects of vernakalant on human resistance artery tone and ventricular muscle contractile function suggests that direct vasorelaxant and inotropic effects do not underlie the rare hypotensive events observed clinically with vernakalant, raising the possibility that secondary (eg, reflex) effects may mediate these events. The demonstration of negative inotropic effects with flecainide in the human ventricular muscle preparations in the absence of an effect on resistance artery tone suggests that the hemodynamic effects of flecainide observed clinically result primarily from direct negative inotropic effects.
Asunto(s)
Anisoles/farmacología , Antiarrítmicos/farmacología , Arterias/efectos de los fármacos , Flecainida/farmacología , Ventrículos Cardíacos/efectos de los fármacos , Pirrolidinas/farmacología , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacología , Vasodilatadores/farmacología , Cardiotónicos/farmacología , Cardiotoxinas/farmacología , Humanos , Técnicas In Vitro , Contracción Miocárdica/efectos de los fármacos , Concentración Osmolar , Piel/irrigación sanguínea , Resistencia Vascular/efectos de los fármacos , Vasodilatación/efectos de los fármacosAsunto(s)
Anticuerpos Antivirales/uso terapéutico , Betacoronavirus/inmunología , Infecciones por Coronavirus/terapia , Inmunoglobulinas Intravenosas/administración & dosificación , Neumonía Viral/terapia , Anticuerpos Antivirales/efectos adversos , Anticuerpos Antivirales/inmunología , COVID-19 , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Humanos , Inmunización Pasiva/efectos adversos , Inmunización Pasiva/métodos , Inmunoglobulinas Intravenosas/efectos adversos , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/virología , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/inmunología , Resultado del Tratamiento , Sueroterapia para COVID-19RESUMEN
Antithrombotic therapy is central to the management of atrial fibrillation. This analysis from the RHYTHM-atrial fibrillation (RHYTHM-AF) registry explored the appropriateness of antithrombotic therapy in relation to stroke risk and atrial fibrillation duration in patients with atrial fibrillation. RHYTHM-AF, a prospective multinational registry, enrolled consecutive adult patients with atrial fibrillation considered for cardioversion. We compared the type of antithrombotic therapy administered at the time of cardioversion and at discharge with stroke risk ("high stroke risk" defined by CHA2DS2-VASc >1) and duration of atrial fibrillation (≤48 vs >48 hours or unknown duration). Of 2,972 patients who were cardioverted (34.5% through pharmacologic cardioversion [PCV] and 65.5% through electrical cardioversion [ECV]), 65% were at high risk of stroke and 30% presented with atrial fibrillation of >48-hour or unknown duration. At the time of PCV and ECV, 36% (n = 242) and 84% (n = 1,075) of high-risk patients, respectively, were taking vitamin K antagonists or heparin. At discharge, these rates increased to 62% (n = 414) and 93% (n = 1,191), respectively. Of all low-stroke risk patients with short-duration atrial fibrillation undergoing PCV (n = 260) and ECV (n = 111), 7% (n = 17) and 30% (n = 33), respectively, were taking vitamin K antagonists or heparin at the time of cardioversion. At discharge, these rates increased to 19% (n = 50) and 40% (n = 44), respectively. In conclusion, ECV was frequently performed under appropriate antithrombotic therapy for most high-risk patients with atrial fibrillation, whereas PCV was frequently performed without appropriate antithrombotic therapy. To enhance pericardioversion stroke prevention, cardioversion algorithms should focus less on the type of conversion and more on stroke risk factors and atrial fibrillation duration.
Asunto(s)
Anticoagulantes/administración & dosificación , Fibrilación Atrial/terapia , Cardioversión Eléctrica/métodos , Accidente Cerebrovascular/prevención & control , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Coagulación Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ecocardiografía Transesofágica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Accidente Cerebrovascular/sangre , Resultado del TratamientoRESUMEN
Coronary artery development is a complex vasculogenic process that begins shortly after heart looping. Coronary vasculogenesis is regulated by the myocardium, but is spatially and temporally dependent on the epicardium and its precursor, the proepicardial organ, for the provision of coronary vascular progenitor cells. Better understanding of the mechanisms of coronary artery development may clarify mechanisms of disease and suggest new potential therapies for disorders of the coronary vasculature.