RENATO SAMY ASSAD
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- Beneficial Effects of Vasopressors on Right Ventricular Function in Experimental Acute Right Ventricular Failure in a Rabbit Model(2012) APITZ, Christian; HONJO, Osami; FRIEDBERG, Mark K.; ASSAD, Renato S.; ARSDELL, Glen Van; HUMPL, Tilman; REDINGTON, Andrew N.Background An acute increase in right ventricular (RV) afterload leads to RV dilation, reduced systolic function, and low cardiac output. It has previously been shown, experimentally, that an additional increase of left ventricular afterload by aortic constriction can reverse some of these changes. We studied the clinically more relevant effects of intravenous vasopressors on this phenomenon in an animal model. Methods Acute RV failure was induced by pulmonary artery constriction in adult New Zealand white rabbits. We then assessed the effect of aortic constriction on the functional performance of the failing RV using conductance catheters. We compared the impact of aortic constriction on RV contractility with the effects of 0.05, 0.1, 0.5, and 1 mcg/kg x min(-1) norepinephrine and epinephrine. Results Aortic constriction lead to increased RV end-systolic pressure-volume relation (RVESPVR 3.2 (+/-0.6) versus 5.2 (+/-0.7) mm Hg/mL (p = 0.0002). Cardiac output (131 (+/-23.7) versus 134.8 (+/-32.5) mL/min), and heart rate remained unchanged. Administration of norepinephrine and epinephrine lead to similar effects on RV contractility with the maximum increase in RVESPVR observed with 0.5 mcg/kg x min(-1) norepinephrine (RVESPVR 4.8 (+/-0.4) mm Hg/mL, p = 0.007). However, in contrast to aortic constriction, cardiac output also markedly increased during vasopressor therapy, the most significant effect seen with 1 mcg/kg x min(-1) epinephrine (214.8 (+/-46.8) mL/min, p = 0.04). Conclusions Aortic constriction improves RV contractility but not cardiac output in acute right heart failure. A comparable effect on RV functional performance with increased cardiac output was achieved by administration of systemic vasopressors. These data may have implications for management of clinical right heart failure.
- Reversible pulmonary trunk banding: VII. Stress echocardiographic assessment of rapid ventricular hypertrophy in young goats(2013) FAVARO, Gustavo A. G.; ASSAD, Renato S.; ABDUCH, Maria C. D.; SILVA, Gustavo J. J.; GOMES, Guilherme S.; ANDRADE, Jose L.; KRIEGER, Jose E.; MOREIRA, Luiz Felipe P.Background: Ventricle retraining with abrupt systolic overload can cause myocardial edema and necrosis, followed by late ventricular failure. Intermittent systolic overload could minimize the inadequacy of conventional pulmonary artery banding. The present study compared ventricle function under dobutamine stress in 2 protocols of systolic overload in young goats. Methods: Nineteen young goats were divided into 3 groups: sham (n = 7; no systolic pressure overload), continuous (n = 6; systolic overload maintained for 96 hours), and intermittent (n = 6; 4 periods of 12-hour systolic overload, paired with a 12-hour resting period). Echocardiographic and hemodynamic evaluations were performed daily. The myocardial performance index and ejection fraction were evaluated at rest and during dobutamine stress. The goats were then killed for morphologic evaluation. Results: The intermittent group underwent less systolic overload than the continuous group (P <. 05). Nevertheless, both groups had increased right ventricular and septal masses compared with the sham group (P <. 0002). Echocardiography revealed a major increase in right ventricular wall thickness in the intermittent group (+64.8% +/- 23.37%) compared with the continuous group (+43.9% +/- 19.26%; P = .015). Only the continuous group remained with significant right ventricular dilation throughout the protocol (P <. 001). The intermittent group had a significantly better myocardial performance index at the end of the protocol, under resting and dobutamine infusion, compared with the continuous group (P <. 012). Conclusions: Both systolic overload protocols have induced rapid right ventricular hypertrophy. However, only the intermittent group had better preservation of right ventricular function at the end of the protocol, both at rest and during dobutamine infusion. (J Thorac Cardiovasc Surg 2013; 145:1345-51)
- Reversible pulmonary trunk banding. VI: Glucose-6-phosphate dehydrogenase activity in rapid ventricular hypertrophy in young goats(2011) ASSAD, Renato S.; ATIK, Fernando A.; OLIVEIRA, Fernanda S.; FONSECA-ALANIZ, Miriam H.; ABDUCH, Maria C. D.; SILVA, Gustavo J. J.; FAVARO, Gustavo G.; KRIEGER, Jose E.; STOLF, Noedir A. G.Objective: Increased myocardial glucose-6-phosphate dehydrogenase (G6PD) activity occurs in heart failure. This study compared G6PD activity in 2 protocols of right ventricle (RV) systolic overload in young goats. Methods: Twenty-seven goats were separated into 3 groups: sham (no overload), continuous (continuous systolic overload), and intermittent (four 12-hour periods of systolic overload paired with a 12-hour resting period). During a 96-hour protocol, systolic overload was adjusted to achieve a 0.7 RV/aortic pressure ratio. Echocardiographic and hemodynamic evaluations were performed before and after systolic overload every day postoperatively. After the study period, the animals were humanely killed for morphologic and G6PD tissue activity assessment. Results: A 92.1% and 46.5% increase occurred in RV and septal mass, respectively, in the intermittent group compared with the sham group; continuous systolic overload resulted in a 37.2% increase in septal mass. A worsening RV myocardial performance index occurred in the continuous group at 72 hours and 96 hours, compared with the sham (P <.039) and intermittent groups at the end of the protocol (P <.001). Compared with the sham group, RV G6PD activity was elevated 130.1% in the continuous group (P = .012) and 39.8% in the intermittent group (P = .764). Conclusions: Continuous systolic overload for ventricle retraining causes RV dysfunction and upregulation of myocardial G6PD activity, which can elevate levels of free radicals by NADPH oxidase, an important mechanism in the pathophysiology of heart failure. Intermittent systolic overload promotes a more efficient RV hypertrophy, with better preservation of myocardial performance and and less exposure to hypertrophic triggers. (J Thorac Cardiovasc Surg 2011;142:1108-13)
- Reversible pulmonary trunk banding. IX. G6PD activity of adult goat myocardium submitted to ventricular retraining(2013) ASSAD, Renato Samy; MIANA, Leonardo Augusto; FONSECA-ALANIZ, Miriam Helena; ABDUCH, Maria Cristina Donadio; SILVA, Gustavo Jose Justo da; OLIVEIRA, Fernanda Santos de; MOREIRA, Luiz Felipe Pinho; KRIEGER, Jose EduardoObjective: Increased glucose 6-phosphate dehydrogenase activity has been demonstrated in heart failure. This study sought to assess myocardial glucose 6-phosphate dehydrogenase activity in retraining of the subpulmonary ventricle of adult goats. Methods: Eighteen adult goats were divided into three groups: traditional (fixed banding), sham, and intermittent (adjustable banding, daily 12-hour systolic overload). Systolic overload (70% of systemic pressure) was maintained during a 4-week period. Right ventricle, pulmonary artery and aortic pressures were measured throughout the study. All animals were submitted to echocardiographic and hemodynamic evaluations throughout the protocol. After the study period, the animals were killed for morphological and glucose 6-phosphate dehydrogenase activity assessment. Results: A 55.7% and 36.7% increase occurred in the intermittent and traditional right ventricle masses, respectively, when compared with the sham group (P<0.05), despite less exposure of intermittent group to systolic overload. No significant changes were observed in myocardial water content in the 3 groups (P=0.27). A 37.2% increase was found in right ventricle wall thickness of intermittent group, compared to sham and traditional groups (P<0.05). Right ventricle glucose 6-phosphate dehydrogenase activity was elevated in the traditional group, when compared to sham and intermittent groups (P=0.05). Conclusion: Both study groups have developed similar right ventricle hypertrophy, regardless less systolic overload exposure of intermittent group. Traditional systolic overload for adult subpulmonary ventricle retraining causes upregulation of myocardial glucose 6-phosphate dehydrogenase activity. It may suggest that the undesirable ""pathologic systolic overload"" is influenced by activation of penthose pathway and cytosolic Nicotinamide adenine dinucleotide phosphate availability. This altered energy substrate metabolism can elevate levels of free radicals by Nicotinamide adenine dinucleotide phosphate oxidase, an important mechanism in the pathophysiology of heart failure.
- When the description of physiology adds to the morphological diagnosis and guides the analysis of clinical and surgical management(2022) AIELLO, Vera Demarchi; ASSAD, Renato Samy
- Reversible Pulmonary Trunk Banding VIII: Intermittent Overload Causes Harmless Hypertrophy in Adult Goat(2013) MIANA, Leonardo A.; ASSAD, Renato S.; ABDUCH, Maria C. D.; SILVA, Gustavo J. J.; NOGUEIRA, Ananda R.; AIELLO, Vera D.; MOREIRA, Luiz Felipe P.Background. Traditional pulmonary artery banding (PAB) is not always suitable for mature subpulmonary ventricle retraining. We sought to assess in detail the myocardial morphologic adaptations of two different protocols for inducing right ventricular (RV) hypertrophy in an adult animal model. Methods. Eighteen adult goats were distributed into three groups: sham (no systolic overload), traditional (continuous systolic overload), and intermittent (daily 12-hour systolic overload). Systolic overload was adjusted to achieve a 0.7 RV-to-aortic pressure ratio. All animals underwent weekly echocardiographic studies, and hemodynamic evaluations were performed 3 times a week. After 4 weeks, the animals were humanely killed for morphologic assessment. Results. A 37.2% increase was observed in the RV wall thickness of the intermittent group (p < 0.05), but no significant echocardiographic changes were observed in the other two groups. The intermittent and traditional groups had a 55.7% and 36.7% increase in RV mass, respectively, compared with the sham group (p < 0.05). No differences were observed in myocardial water content of the three groups (p = 0.27). RV myocardial fiber and nuclei diameters were increased in the intermittent group compared with the sham group (p < 0.05). The area of collagen deposition in the RV interstitium was increased 98% in traditional group compared with the sham group (p < 0.05). No significant cellular proliferation occurred in any group. Conclusions. This study suggests that a more effective and harmless hypertrophy can be achieved in adult animals using intermittent PAB compared with the traditional approach. (Ann Thorac Surg 2013;95:1422-8) (c) 2013 by The Society of Thoracic Surgeons
- Ischemic preconditioning does not prevent placental dysfunction induced by fetal cardiac bypass(2022) ASSAD, Renato S.; GUEDES, Marcelo G. A.; AIELLO, Vera D.; THOMAZ, Petronio G.; ZANONI, Fernando L.; SAITO, Mauricio; SILVA, Ana Paula N. da; SILVA, Raphael dos S. Coutinho e; V, Marcelo Pinto; JATENE, Marcelo B.; MOREIRA, Luiz Felipe P.Background Remote ischemic preconditioning (rIPC) has been applied to attenuate tissue injury. We tested the hypothesis that rIPC applied to fetal lambs undergoing cardiac bypass (CB) reduces fetal systemic inflammation and placental dysfunction. Methods Eighteen fetal lambs were divided into three groups: sham, CB control, and CB rIPC. CB rIPC fetuses had a hindlimb tourniquet applied to occlude blood flow for four cycles of a 5-min period, followed by a 2-min reperfusion period. Both study groups underwent 30 min of normothermic CB. Fetal inflammatory markers, gas exchange, and placental and fetal lung morphological changes were assessed. Results The CB rIPC group achieved higher bypass flow rates (p < .001). After CB start, both study groups developed significant decreases in PaO2, mixed acidosis, and increased lactate levels (p < .0004). No significant differences in tissular edema were observed on fetal lungs and placenta (p > .391). Expression of Toll-like receptor 4 and intercellular adhesion molecule-1 in the placenta and fetal lungs did not differ among the three groups, as well as with vascular cell adhesion molecule-1 (VCAM-1) of fetal lungs (p > .225). Placental VCAM-1 expression was lower in the rIPC group (p < .05). Fetal interleukin-1 (IL-1) and thromboxane A2 (TXA2) levels were lower at 60 min post-CB in the CB rIPC group (p < .05). There were no significant differences in tumor necrosis factor-alpha, prostaglandin E2, IL-6, and IL-10 plasma levels of the three groups at 60-min post-bypass (p > .133). Conclusion Although rIPC allowed increased blood flow during fetal CB and decreased IL-1 and TXA2 levels and placental VCAM-1, it did not prevent placental dysfunction in fetal lambs undergoing CB.
- Intra-aortic balloon pump in cardiogenic shock: state of the art(2017) THOMAZ, PETRONIO GENEROSO; MOURA JÚNIOR, LEONEL ADELINO; MURAMOTO, GIOVANA; ASSAD, RENATO SAMYABSTRACT The clinical definition of cardiogenic shock is that of a low cardiac output and evidence of tissue hypoxia in the presence of adequate blood volume. Cardiogenic shock is the main cause of death related to acute myocardial infarction (AMI), with a mortality rate of 45-70% in the absence of aggressive and highly specialized technical care. The intra-aortic balloon pump (IABP) is one of the most widely used mechanical assisting devices. During the last two decades, about 42% of patients with AMI who evolved with cardiogenic shock received mechanical circulatory assistance with IABP. Its clinical indication has been based on non-randomized studies and registry data. Recent studies have shown that the use of IABP did not reduce 30-day mortality in patients with AMI and cardiogenic shock treated with the strategy of early myocardial revascularization as the planned primary objective. The guidelines of the American Heart Association and of the European Society of Cardiology have reassessed their recommendations based on the results of meta-analyzes, including the IABP-SCHOCK II Trial study, which did not evidence an increase in survival of patients who received mechanical support with IABP. This review article addresses the clinical impact of IABP use in the cardiogenic shock caused by AMI.
- Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload(2012) APITZ, Christian; HONJO, Osami; HUMPL, Tilman; LI, Jing; ASSAD, Renato S.; CHO, Mi Y.; HONG, James; FRIEDBERG, Mark K.; REDINGTON, Andrew N.Objectives: Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Methods: Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB+AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Results: Contractile performance was significantly improved in the PAB+AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB+AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor beta genes. Conclusions: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV.
- Can total bronchopleural fistulas from complete stump dehiscence be endoscopically treated?(2017) SCORDAMAGLIO, Paulo Rogerio; TEDDE, Miguel Lia; MINAMOTO, Helio; ASSAD, Renato Samy; FERNANDES, Paulo Manuel PegoOBJECTIVES: Bronchopleural fistula (BPF) is an uncommon complication following a lung resection to address various conditions. BPFs are associated with high morbidity and mortality rates. This study evaluated the endoscopic treatment of 'total' BPFs using the Occlutech-Figulla (R) cardiac device at a single centre. METHODS: We selected nine patients with chronic and complete BPFs. Under direct bronchoscopic visualization, the BPFs were treated using the Occlutech-Figulla device. The patients were followed up for 12 months to determine the treatment level and complications. RESULTS: The procedure had a favourable outcome in three patients, resulting in complete fistula closure. Two patients had partial closure and showed improvements in their clinical conditions. In two other cases, closure of the bronchial stump was unsuccessful using this method. Two patients died from causes unrelated to the procedure or the device. During the follow-up period, no complications related to infection or device-related injuries were reported. CONCLUSIONS: In patients without clinical conditions that require surgical treatment, the Occlutech-Figulla cardiac device can be a safe and effective method for the endoscopic treatment of large BPFs resulting from complete dehiscence of a bronchial stump. No severe events were reported.