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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- 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. 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.
bookPart Cardiologia e cirurgia cardiovascular fetal(2013) PICCOLI JR., Antonio Luiz; NICOLOSO, Luis Henrique S.; ZIELINSKY, Paulo; ASSAD, Renato S.- 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