LUCAS FARACO SOBRADO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
4 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.
- Surgery in Brazilian Health Care: funding and physician distribution(2017) ALONSO, NIVALDO; MASSENBURG, BENJAMIN B.; GALLI, RAFAEL; SOBRADO, LUCAS; BIROLINI, DARIOABSTRACT Objective: to analyze demographic Brazilian medical data from the national public healthcare system (SUS), which provides free universal health coverage for the entire population, and discuss the problems revealed, with particular focus on surgical care. Methods: data was obtained from public healthcare databases including the Medical Demography, the Brazilian Federal Council of Medicine, the Brazilian Institute of Geography and Statistics, and the National Database of Healthcare Establishments. Density and distribution of the medical workforce and healthcare facilities were calculated, and the geographic regions were analyzed using the public private inequality index. Results: Brazil has an average of two physicians for every 1,000 inhabitants, who are unequally distributed throughout the country. There are 22,276 board certified general surgeons in Brazil (11.49 for every 100,000 people). The country currently has 257 medical schools, with 25,159 vacancies for medical students each year, with only around 13,500 vacancies for residency. The public private inequality index is 3.90 for the country, and ranges from 1.63 in the Rio de Janeiro up to 12.06 in Bahia. Conclusions: A significant part of the local population still faces many difficulties in accessing surgical care, particularly in the north and northeast of the country, where there are fewer hospitals and surgeons. Physicians and surgeons are particularly scarce in the public health system nationwide, and better incentives are needed to ensure an equal public and private workforce.
conferenceObject Low Doses of Ranolazine and Dronedarone in Combination Exert Potent Protection against Atrial Fibrillation and Vulnerability to Ventricular Arrhythmias during Acute Myocardial Ischemia(2012) VERRIER, Richard L.; PAGOTTO, Vitor P.; KANAS, Alexandre F.; SOBRADO, Marcel F.; NEARING, Bruce D.; ZENG, Dewan; BELARDINELLI, Luiz- Selective late sodium current blockade with GS-458967 markedly reduces ischemia-induced atrial and ventricular repolarization alternans and ECG heterogeneity(2014) BONATTI, Rodolfo; SILVA, Ana Flavia Garcia; BATATINHA, Americo Pereira; SOBRADO, Lucas F.; MACHADO, Ananda Dianni; VARONE, Bruno B.; NEARING, Bruce D.; BELARDINELLI, Luiz; VERRIER, Richard L.BACKGROUND Ischemic heart disease is associated with dual risk for atrial and ventricular arrhythmias. OBJECTIVE We examined whether selectively targeting late sodium channel current (I-Na) with 65-458967 (hereafter 65967) can reduce cardiac electrical instability and compared its effects to a clinically relevant dose of flecainide. METHODS Electrode catheters were positioned on the left atrial appendage and left ventricle of anesthetized pigs to monitor repolarization alternans and electrocardiographic heterogeneity before and during left circumflex coronary artery stenosis (75% flow reduction) before and after GS967 (0.4 mg/kg, intravenously [IV]) or ftecainide (1 mg/kg, IV, bolus over 2 minutes followed by 1 mg/(kg . h), IV, for 1 hour) administration. RESULTS Left circumflex coronary artery stenosis increased atrial repolarization alternans by 520% (from 9.4 +/- 1.2 to 58.3 +/- 11.3 mu V; P = .029) and 1-wave alternans by 1038% (from 30.7 +/- 8.2 to 349.3 +/- 103.8 mu V; P = .049). GS967 prevented ischemia-induced increases in alternans in the left atrium (9.3 +/- 5.6 mu V vs 58.3 +/- 11.3 mu V; P = .023) and Left ventricle (217.9 +/- 95.8 mu V vs 349.3 +/- 103.8 mu V; P < .001) (n = 7). GS967 reduced ischemia-induced increases in depolarization heterogeneity (atrium: from 45% to 28%; ventricle: from 92% to 51%) and repolarization heterogeneity (atrium: 43% to 23%; ventricle: 137% to 91%). GS967 did not alter heart rate, arterial blood pressure, PR and QT intervals, or QRS duration, but it mildly decreased contractility (left ventricular dP/dt) during ischemia, which was consistent with late I-Na inhibition. Flecainide (n = 7) amplified ischemia-induced increase in atrial and ventricular repolarization alternans, electrocardiographic heterogeneity, and ventricular fibrillation incidence. CONCLUSION Selective late IN, inhibition with 65967 exerts potent protective effects against ischemia-induced depolarization and repolarization abnormalities in both atria and ventricles.