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
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- 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)
- Adverse Biventricular Remodeling in Isolated Right Ventricular Hypertension Is Mediated by Increased Transforming Growth Factor-beta 1 Signaling and Is Abrogated by Angiotensin Receptor Blockade(2013) FRIEDBERG, Mark K.; CHO, Mi-Young; LI, Jing; ASSAD, Renato S.; SUN, Mei; ROHAILLA, Sagar; HONJO, Osami; APITZ, Christian; REDINGTON, Andrew N.The pressure-loaded right ventricle (RV) adversely affects left ventricular (LV) function. We recently found that these ventricular-ventricular interactions lead to LV myocardial fibrosis through transforming growth factor-beta 1 (TGF-beta 1) signaling. We investigated the mechanisms mediating biventricular fibrosis in RV afterload and their potential modification by angiotensin receptor blockade. An adjustable pulmonary artery band (PAB) was placed in rabbits. In sham-operated control rabbits, the band was left uninflated (n = 6). In the RV afterload group, the PAB was sequentially inflated to generate systemic RV pressure at 28 days (n = 8). In a third group, the PAB was inflated to systemic levels, and the angiotensin receptor blocker losartan was added (n = 6). Five weeks after surgery, the animals were killed for assessments of biventricular hypertrophy, fibrosis, apoptosis, and the components of their signaling pathways. PAB animals developed biventricular hypertrophy, fibrosis, and apoptosis, versus sham rabbits, in which these conditions were decreased with losartan. RV and LV TGF-beta 1, connective tissue growth factor (CTGF) (CCN2), endothelin-1 (ET-1), endothelin receptor B, and matrix metalloproteinase 2/9 mRNA levels were increased in PAB animals versus sham animals, and decreased with losartan. Given the marked biventricular CTGF up-regulation in PAB and down-regulation with losartan, we investigated CTGF signaling. RV and LV Smad 2/3/4 protein levels and LV RhoA mRNA levels were increased with PAB and reduced with losartan. In conclusion, isolated RV afterload induces biventricular fibrosis and apoptosis, which are reduced by angiotensin receptor blockade. Adverse ventricular-ventricular interactions induced by isolated RV afterload appear to be mediated through TGF-beta 1-CTGF and ET-1 pathways.
- 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)
conferenceObject Reversible Pulmonary Trunk Banding. XI: Myocardial Vascular Endothelial Growth Factor Expression of Young Goats Submitted to Rapid Ventricle Retraining(2016) ASSAD, Renato S.; ROCHA, Eduardo A.; MENICONI, Tiago A.; ABDUCH, Maria Cristina D.; MOREIRA, Luiz Felipe P.; AIELLO, Vera D.; JATENE, Fabio B.- Reversible pulmonary trunk banding: Myocardial vascular endothelial growth factor expression in young goats submitted to ventricular retraining(2020) ASSAD, Renato S.; V, Eduardo A. Rocha; AIELLO, Vera D.; MENICONI, Tiago A.; ABDUCH, Maria C. D.; THOMAZ, Petronio G.; JATENE, Marcelo B.; MOREIRA, Luiz F. P.Background Ventricle retraining has been extensively studied by our laboratory. Previous studies have demonstrated that intermittent overload causes a more efficient ventricular hypertrophy. The adaptive mechanisms involved in the ventricle retraining are not completely established. This study assessed vascular endothelial growth factor (VEGF) expression in the ventricles of goats submitted to systolic overload. Methods Twenty-one young goats were divided into 3 groups (7 animals each): control, 96-hour continuous systolic overload, and intermittent systolic overload (four 12-hour periods of systolic overload paired with 12-hour resting period). During the 96-hour protocol, systolic overload was adjusted to achieve a right ventricular (RV) / aortic pressure ratio of 0.7. Hemodynamic evaluations were performed daily before and after systolic overload. Echocardiograms were obtained preoperatively and at protocol end to measure cardiac masses thickness. At study end, the animals were killed for morphologic evaluation and immunohistochemical assessment of VEGF expression. Results RV-trained groups developed hypertrophy of RV and septal masses, confirmed by increased weight and thickness, as expected. In the study groups, there was a small but significantly increased water content of the RV and septum compared with those in the control group (p<0.002). VEGF expression in the RV myocardium was greater in the intermittent group (2.89% +/- 0.41%) than in the continuous (1.80% +/- 0.19%) and control (1.43% +/- 0.18%) groups (p<0.023). Conclusions Intermittent systolic overload promotes greater upregulation of VEGF expression in the sub-pulmonary ventricle, an adaptation that provides a mechanism for increased myocardial perfusion during the rapid myocardial hypertrophy of young goats.
bookPart Cardiologia e cirurgia cardiovascular fetal(2013) PICCOLI JR., Antonio Luiz; NICOLOSO, Luis Henrique S.; ZIELINSKY, Paulo; ASSAD, Renato S.conferenceObject Remote Ischemic Preconditioning Does Not Prevent Placental Dysfunction Induced by Extrcorporeal Circulation in Fetal Lambs(2019) ASSAD, Renato S.; GUEDES, Marcelo G.; AIELLO, Vera D.; THOMAZ, Petronio G.; ZANONI, Fernando L.; ARASHIRO, Ana Cristina A.; SILVA, Ana Paula N. da; SILVA, Raphael S. Coutinho e; FALOPPA, Ana Cristina B.; PINTO, Marcelo V.; JATENE, Marcelo B.; MOREIRA, Luiz Felipe P.- 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.