JULIO AMERICO PEREIRA BATATINHA
Projetos de Pesquisa
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
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- Combined Actions of Ivabradine and Ranolazine Reduce Ventricular Rate During Atrial Fibrillation(2015) VERRIER, Richard L.; SILVA, Ana F. G.; BONATTI, Rodolfo; BATATINHA, Julio A. P.; NEARING, Bruce D.; LIU, Gongxin; RAJAMANI, Sridharan; ZENG, Dewan; BELARDINELLI, LuizDrug Combination Reduces Ventricular Rate in AF IntroductionVentricular rate during atrial fibrillation (AF) can be reduced by slowing atrioventricular (AV) node conduction and/or by decreasing dominant frequency of AF. We investigated whether combined administration of ivabradine and ranolazine reduces ventricular rate during AF. Methods and ResultsIvabradine (maximum clinical dose, 0.25 mg/kg, and 0.10 mg/kg, i.v.) and ranolazine (2.4 mg/kg, i.v., bolus followed by 0.135 mg/kg/min) were studied in an anesthetized pig (N = 16) model of AF. Combined administration of 0.25 mg/kg ivabradine with ranolazine reduced ventricular rate during AF by 51.9 9.7 beats/min (23%, P = 0.017) and dominant frequency of AF by 2.8 +/- 0.5 Hz (32%, P = 0.005). It increased PR (P = 0.0002, P = 0.0007) and A-H intervals (P = 0.047, P = 0.002) during pacing at 130 and 180 beats/min, respectively, to a greater degree than additive effects of single agents. Combined administration of 0.1 mg/kg ivabradine with ranolazine exceeded additive effects of single agents on A-H intervals and dominant frequency of AF. Moreover, ranolazine potentiated low-dose ivabradine's reduction in ventricular rate, as combined administration more than doubled effects of the higher ivabradine dose alone and was similar to the combination with the higher dose. Neither drug nor their combination affected contractility (left ventricular [LV] dP/dt), QT or His-ventricular (H-V) intervals, or mean arterial pressure during sinus rhythm or AF. ConclusionCombined administration of ivabradine and ranolazine at clinically safe levels decreases ventricular rate during AF by reducing AV node conduction and AF dominant frequency without QT prolongation or depression in contractility. Targeting these actions offers intrinsic advantages over conventional nodal agents, which can reduce contractility.
article 1 Citação(ões) na Scopus The Selective Late Sodium Current Inhibitor Eleclazine, Unlike Amiodarone, Does Not Alter Defibrillation Threshold or Dominant Frequency of Ventricular Fibrillation(2017) SILVA, Ana F. G.; BONATTI, Rodolfo; BATATINHA, Julio A. P.; NEARING, Bruce D.; ZENG, Dewan; BELARDINELLI, Luiz; VERRIER, Richard L.Introduction: We examined the effects of the selective late INa inhibitor eleclazine on the 50% probability of successful defibrillation (DFT50) before and after administration of amiodarone to determine its suitability for use in patients with implantable cardioverter defibrillators (ICDs). Methods and Results: In 20 anesthetized pigs, transvenous active-fixation cardiac defibrillation leads were fluoroscopically positioned into right ventricular apex through jugular vein. ICDs were implanted subcutaneously. Dominant frequency of ventricular fibrillation was analyzed by fast Fourier transform. The measurements were made before drug administration (control), and at 40 minutes after vehicle, eleclazine (2 mg/kg, i.v., bolus over 15 minutes), or subsequent/single amiodarone administration (10 mg/kg, i.v., bolus over 10 minutes). Eleclazine did not alter DFT50, dominant frequency, heart rate, or mean arterial pressure (MAP). Subsequent amiodarone increased DFT50 (P = 0.006), decreased dominant frequency (P = 0.022), and reduced heart rate (P = 0.031) with no change in MAP. Amiodarone alone increased DFT50 (P = 0.005; NS compared to following eleclazine) and decreased dominant frequency (P = 0.003; NS compared to following eleclazine). Conclusion: Selective late INa inhibition with eleclazine does not alter DFT50 or dominant frequency of ventricular fibrillation when administered alone or in combination with amiodarone. Accordingly, eleclazine would not be anticipated to affect the margin of defibrillation safety in patients with ICDs.- Volumetric evaluation of pharyngeal segments in obstructive sleep apnea patients(2018) RODRIGUES, Marcos Marques; PEREIRA FILHO, Valfrido Antonio; GABRIELLI, Mario Francisco Real; OLIVEIRA, Talles Fernando Medeiros de; BATATINHA, Julio Americo Pereira; PASSERI, Luis AugustoIntroduction: Obstructive sleep apnea occurs by recurrent collapse of the upper airway during sleep, resulting in total (apnea) or partial (hypopnea) reduction of the airflow and has intimate relation with changes in the upper airway. Cone Beam CT allows the analysis of the upper airway and its volume by three-dimensional reconstruction. Objective: To evaluate a possible correlation between the volume of the upper airway and the severity of the obstructive sleep apnea. Methods: A retrospective study was performed reviewing polysomnographic data and Cone Beam CT records of 29 patients (13 males and 16 females). The correlation between the volume of the nasopharynx, the oropharynx and the total superior pharynx with the AHI was assessed by Pearson's rank correlation coefficient. Results: The obstructive sleep apnea severity division was: ten patients had severe, 7 had moderate, 6 had mild and 6 of them were healthy. The correlation between the nasopharynx, the oropharynx and the total superior pharynx volumes and the Apnea-Hypopnea-Index was respectively: -0.415 (p=0.025), 0.186 (p=0.334) and -0329 (p=0.089). The Spearman's rank controlled by the Body Mass Index, the age and the gender was: -0.206 (p=0.304), -0.155 (p=0.439) and 0.242 (p=0.284). Conclusion: There is no correlation between the volume of the airway and the obstructive sleep apnea, assessed by Apnea-Hypopnea-Index and controlled by the Body Mass Index, the age and the gender. The volume of the upper airways as an isolated parameter did not correlate to the severity of the obstructive sleep apnea syndrome, and should be evaluated together with other factors. (C) 2017 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial.
conferenceObject Clinical, psychological, and molecular aspects of a large androgen insensitivity syndrome cohort(2023) BATISTA, Rafael Loch; INACIO, Marlene; AFONSO, Ane Caroline; CARVALHO, Filomena; RAMOS, Raquel; CRAVEIRO, Flora; DALLAGO, Renata; FERRARI, Maria Tereza; BATATINHA, Julio; NISHI, Miriam; DOMENICE, Sorahia; MENDONCA, Berenice Bilharinho- Conjoined twins - twenty years' experience at a reference center in Brazil(2013) TANNURI, Ana Cristina Aoun; BATATINHA, Julio Americo Pereira; VELHOTE, Manoel Carlos Prieto; TANNURI, UenisOBJECTIVE: This study reports on the experience of one hospital regarding the surgical aspects, anatomic investigation and outcomes of the management of 21 conjoined twin pairs over the past 20 years. METHODS: All cases of conjoined twins who were treated during this period were reviewed. A careful imaging evaluation was performed to detail the abdominal anatomy (particularly the liver), inferior vena cava, spleen and pancreas, either to identify the number of organs or to evaluate the degree of organ sharing. RESULTS: There were eight sets of ischiopagus twins, seven sets of thoracopagus twins, three sets of omphalopagus twins, two sets of thoraco-omphalo-ischiopagus twins and one set of craniopagus twins. Nine pairs of conjoined twins could not be separated due to the complexity of the organs (mainly the liver and heart) that were shared by both twins; these pairs included one set of ischiopagus twins, six sets of thoracopagus twins and one set of thoraco-omphalo-ischiopagus twins. Twelve sets were separated, including seven sets of ischiopagus twins, three sets of omphalopagus twins, one set of thoracopagus twins and one set of craniopagus conjoined twins. The abdominal wall was closed in the majority of patients with the use of mesh instead of the earlier method of using tissue expanders. The surgical survival rate was 66.7%, and one pair of twins who did not undergo separation is currently alive. CONCLUSION: A detailed anatomic study of the twins and surgical planning must precede separation. A well-prepared pediatric surgery team is sufficient to surgically manage conjoined twins.
conferenceObject IVABRADINE CAUSES MARKED USE-DEPENDENT SLOWING OF AV NODE CONDUCTION AND REDUCES VENTRICULAR RATE DURING ATRIAL FIBRILLATION(2014) VERRIER, Richard; BONATTI, Rodolfo; SILVA, Ana Flavia Garcia; BATATINHA, Julio A. P.; NEARING, Bruce; ZENG, Dewan; BELARDINELLI, Luiz- Correlation Between the Friedman Staging System and the Upper Airway Volume in Patients With Obstructive Sleep Apnea(2015) RODRIGUES, Marcos Marques; GABRIELLI, Mario Francisco Real; WATANABE, Evenson Raphael; BATATINHA, Julio Americo Pereira; PEREIRA FILHO, Valfrido Antonio; PASSERI, Luis AugustoPurpose: This study was designed to evaluate the correlation between computed tomography findings and data from the physical examination and the Friedman Staging System (FSS) in patients with obstructive sleep apnea (OSA). Patients and Methods: We performed a retrospective evaluation by reviewing the medical records of 33 patients (19 male and 14 female patients) with a mean body mass index of 30.38 kg/m(2) and mean age of 49.35 years. Among these patients, 14 presented with severe OSA, 7 had moderate OSA, 7 had mild OSA, and 5 were healthy. Results: The patients were divided into 2 groups according to the FSS: Group A comprised patients with FSS stage I or II, and group B comprised patients with FSS stage III. By use of the Fisher exact test, a positive relationship between the FSS stage and apnea-hypopnea index (P = .011) and between the FSS stage and body mass index (P = .012) was found. There was no correlation between age (P = .55) and gender (P = .53) with the FSS stage. The analysis of variance test comparing the upper airway volume between the 2 groups showed P = .018. Conclusions: In this sample the FSS and upper airway volume showed an inverse correlation and were useful in analyzing the mechanisms of airway collapse in patients with OSA. (C) 2015 American Association of Oral and Maxillofacial Surgeons
- 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.
conferenceObject Retrospective Analysis of Individuals with Differences in Sex Development (DSD) in a Brazilian Single-Center Study Across the Lifespan(2023) BATISTA, Rafael; GOMES, Nathalia; BACHEGA, Tania; MADUREIRA, Guiomar; MIRANDA, Mirela; DALLAGO, Renata; TERESA, Maria; LOUSADA, Ferrari Lia; CRAVEIRO, Flora; BATATINHA, Julio; SCALCO, Renata; JORGE, Alexander; COSTA, Elaine; SIRCILI, Maria Helena; DENES, Francisco; INACIO, Marlene; NISHI, Mirian; DOMENICE, Sorahia; MENDONCA, Berenice- I-f inhibition in the atrioventricular node by ivabradine causes rate-dependent slowing of conduction and reduces ventricular rate during atrial fibrillation(2014) VERRIER, Richard L.; BONATTI, Rodolfo; SILVA, Ana F. G.; BATATINHA, Julio A. P.; NEARING, Bruce D.; LIU, Gongxin; RAJAMANI, Sridharan; ZENG, Dewan; BELARDINELLI, LuizBACKGROUND I-f channels are functionally expressed in atrioventricular (AV) nodal tissue. OBJECTIVE The purpose of this study was to address whether the prototypical I-f inhibitor, ivabradine, at clinically safe concentrations can slow AV node conduction to reduce ventricular rate (VR) during atrial fibrillation (AF). METHODS Effects of ivabradine (0.1 mg/kg IV bolus) were studied in an anesthetized Yorkshire pig (N = 7) model of AF and in isolated guinea pig hearts (N = 7). RESULTS Ivabradine reduced heart rate (P = .0001) without affecting mean arterial pressure during sinus rhythm. The agent Lengthened PR intervals in a rate-dependent manner (P = .0009) by 14 +/- 2.7 ms (P = .003) and 25 +/- 3.0 ms (P = .0004) and increased atrial-His (A-H) intervals in a rate-dependent manner (P = .020) by 10 +/- 1.7 ms and 17 +/- 2.8 ms during pacing at 130 and 180 bpm, respectively (both P = .0008). Similar rate-dependent effects were observed in isolated guinea pig hearts. Ivabradine slowed VR during AF from 240 +/- 21 bpm to 211 +/- 25 bpm (P = .041). The ivabradine-induced increase in A-H interval was inversely correlated with VR (r = -0.85, P = .03, at 130 bpm; r = -0.95, P = .003, at 180 bpm). QT and HV intervals, AF dominant frequency (8.5 +/- 0.9 to 8.7 +/- 1.1 Hz, P = NS), mean arterial pressure, and left ventricular dP/dt (1672 +/- 222 to 1889 +/- 229 mm Hg/s, P = NS) during AF were unaffected. CONCLUSION Ivabradine's rate-dependent increase in A-H interval is highly correlated with VR during AF. As dominant frequency was unaltered, AV node conduction slowing during high nodal activation rates appears to be the main mechanism of ivabradine's VR reduction. I-f inhibition in the AV node may provide a promising target to slow VR during AF without depression in contractility.