LUCAS FARACO SOBRADO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- Dronedarone's Inhibition of I-f Current Is the Primary Mechanism Responsible for Its Bradycardic Effect(2013) SOBRADO, Lucas F.; VARONE, Bruno B.; MACHADO, Ananda D.; NEARING, Bruce D.; ZENG, Dewan; BELARDINELLI, Luiz; VERRIER, Richard L.Dronedarone's Bradycardic Effect IntroductionThe mechanism(s) whereby dronedarone reduces sinus rate are not well understood, although L-type calcium channel antagonism, beta-adrenergic blockade, and inhibition of I-f are plausible. Methods and ResultsIn anesthetized pigs, we compared the effects of dronedarone to the prototypical I-f inhibitor, ivabradine, and the L-type calcium channel antagonist diltiazem on heart rate, mean arterial blood pressure (MAP), and contractility. Dronedarone's effects on the phenylephrine-induced rise in MAP and on the chronotropic response to isoproterenol were also investigated. Cumulative doses of dronedarone (0.5mg/kg, i.v., and 5.0mg/kg, i.v.; plasma level: 8016.1 nM) progressively reduced heart rate (P<0.02) without changes in MAP or contractility as assessed by LV dP/dt (N = 6). Ivabradine (0.5mg/kg, i.v.) similarly reduced heart rate (P<0.01) without change in MAP (N = 6). Diltiazem (0.8mg/kg, i.v.) reduced heart rate and MAP and decreased contractility (N = 6). Dronedarone blunted phenylephrine's alpha-receptor-mediated increase in MAP but did not alter the marked beta-adrenergic receptor (BAR)-mediated increase in heart rate induced by isoproterenol. When dronedarone injection was preceded by ivabradine, no further decrease in heart rate or change in MAP was observed (N = 6). ConclusionsDronedarone reduced heart rate without affecting MAP or contractility, effects that differ from L-type calcium channel blockade. Dronedarone did not antagonize BAR stimulation, and its heart-rate lowering effects were eliminated by prior administration of ivabradine. Thus, dronedarone's bradycardic action is likely due to inhibition of I-f and not to blockade of either L-type calcium channels or BAR.
bookPart Desarterialização Transanal Guiada por Doppler Associada a Hemorroidopexia: Resultados Imediatos e Tardios(2013) SOBRADO, Carlos Walter; HORA, José Américo Bacchi; SOBRADO, Lucas Faraco