FERNANDO LUIZ ZANONI
Projetos de Pesquisa
Unidades Organizacionais
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
28 resultados
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conferenceObject Impact of sympathectomy upon myocardium(2019) PESSOA, F. Fernanda; JORDAO, M. R.; FONSECA, K. C. B.; ZANONI, F.; SALEMI, V. M. C.; RIBEIRO, O. N.; SOUZA, L. E.; FERNANDES, F.; IRIGOYEN, M. C.; MOREIRA, L. F. P.; MADY, C.; RAMIRES, F. J. A.conferenceObject Effects of sympathectomy on myocardium(2014) JORDAO, M.; RAMIRES, F.; PESSOA, F.; FONSECA, K.; ZANONI, F.; SOUZA, L.; SALEMI, V.; MADY, C.- Perspectives of bilateral thoracic sympathectomy for treatment of heart failure(2021) SILVA, Raphael dos Santos Coutinho E; ZANONI, Fernando Luiz; SIMAS, Rafael; MOREIRA, Luiz Felipe PinhoSurgical neuromodulation therapies are still considered a last resort when standard therapies have failed for patients with progressive heart failure (HF). Although a number of experimental studies have provided robust evidence of its effectiveness, the lack of strong clinical evidence discourages practitioners. Thoracic unilateral sympathectomy has been extensively studied and has failed to show significant clinical improvement in HF patients. Most recently, bilateral sympathectomy effect was associated with a high degree of success in HF models, opening the perspective to be investigated in randomized controlled clinical trials. In addition, a series of clinical trials showed that bilateral sympathectomy was associated with a decreased risk of sudden death, which is an important outcome in patients with HF. These aspects indicates that bilateral sympathectomy could be an important alternative in the treatment of HF wherein pharmacological treatment barely reaches the target dose.
conferenceObject Bilateral Sympathetic Denervation Improves Left Ventricular Function and Prevents Post-Infarction Chamber Remodeling in Rats(2016) ZANONI, F. L.; MOREIRA, L. F.; SIMAS, R.; SILVA, R. G. da; JATENE, F. B.- HYPERTONIC SALINE SOLUTION REDUCES MESENTERIC MICROCIRCULATORY DYSFUNCTIONS AND BACTERIAL TRANSLOCATION IN A RAT MODEL OF STRANGULATED SMALL BOWEL OBSTRUCTION(2013) ZANONI, Fernando Luiz; CRUZ, Jose Walber Miranda Costa; MARTINS, Joilson Oliveira; BENABOU, Simon; GRECO, Karin Vicente; MORENO, Ana Carolina Ramos; MARTINEZ, Marina Baquerizo; CALDERARO, Franco Ferraro; SILVA, Mauricio Rocha e; SANNOMIYA, PaulinaWe examined the effects of hypertonic saline (HS) on inflammatory, metabolic variables, and bacterial translocation (BT) in rats submitted to intestinal obstruction and ischemia (IO). Male Wistar rats were submitted to IO and treated, 2 h thereafter, with lactated Ringer's (LR) (4 mL/kg per 5 min, i.v.) or HS (7.5% NaCl, 4 mL/kg per 5 min, i.v.). Twenty-four hours after IO, rats were also submitted to enterectomy/enteroanastomosis to resection of necrotized small bowel. Leukocyte-endothelial interactions were investigated by intravital microscopy and the expression of P-selectin and intercellular adhesion molecule 1 by immunohistochemistry. Bacterial cultures of mesenteric lymph nodes, liver, spleen, and blood were used to evaluate BT. Levels of chemokines (cytokine-induced neutrophil chemoattractants 1 and 2), insulin, and corticosterone were determined by enzyme-linked immunosorbent assay. Intestinal histology, serum urea and creatinine levels, and hepatic enzymes activities were performed to evaluate local and remote damage. Relative to IO and LR-treated rats, which exhibited increases in the number of rolling (1.5-fold), adhered (3.5-fold) and migrated (9.0-fold) leukocytes, and increased expression of P-selectin (3-fold) and intercellular adhesion molecule 1 (3-fold) on mesenteric microcirculation, treatment with HS followed by enterectomy reduced leukocyte-endothelial interactions and expression of both adhesion molecules to values attained in sham rats. Serum chemokines were normalized after treatment with both solutions followed by enterectomy. Hypertonic saline-treated rats demonstrated a significant reduction in BT to 50% in liver and spleen samples and bacteremia (14%), compared with 82% of BT in liver and spleen samples of IO and LR-treated rats and bacteremia (57%). Local intestinal damage was attenuated, and renal and hepatic function preserved by treatment with HS followed by enterectomy. Survival rate increased to 86% up to 15 days. Data presented suggest that HS solution followed by enterectomy reduces mesenteric microcirculatory dysfunctions and BT, attenuating local and remote damage in a model of strangulated small bowel obstruction.
conferenceObject LYMPHOCYTE SUBSETS, EXPRESSION OF ADHESION MOLECULES AND APOPTOSIS IN BONE MARROW CELLS OF BRAIN-DEAD RATS(2015) MENEGAT, Laura; SIMAS, Rafael; ZANONI, Fernando; BORELLI, Primavera; JACYSYN, Jacqueline; MOREIRA, Luiz Felipe; SANNOMIYA, Paulina- Bilateral sympathectomy improves postinfarction left ventricular remodeling and function(2017) ZANONI, Fernando Luiz; SIMAS, Rafael; SILVA, Raphael Grillo da; BREITHAUPT-FALOPPA, Ana Cristina; SILVA, Raphael dos Santos Coutinho e; JATENE, Fabio Biscegli; MOREIRA, Luiz Felipe P.Objectives: To evaluate the influence of bilateral or left sympathectomy on left ventricular remodeling and function after myocardial infarction in rats. Methods: Myocardial infarction was induced in rats by ligation of the left anterior descending coronary. Seven days later, rats were divided into 4 groups: the myocardial infarction, myocardial infarction with left sympathectomy, myocardial infarction with bilateral sympathectomy, and sham groups. After 8 weeks, left ventricular function was evaluated with the use of a pressure-volume conductance catheter under steady-state conditions and pharmacological stress. Infarct size and extracellular matrix fibrosis were evaluated, and cardiac matrix metalloproteinases and myocardial inflammatory markers were analyzed. Results: The myocardial infarction and left sympathectomy group had an increased end diastolic volume, whereas the bilateral sympathectomy group had a mean end-diastolic volume similar to that of the sham group (P <. 002). Significant reduction in ejection fraction was observed in the myocardial infarction and left sympathectomy group, whereas it was preserved after bilateral sympathectomy (P < .001). In response to dobutamine, left ventricular contractility increased in sham rats, rising stroke work, cardiac output, systolic volume, end-diastolic volume, ejection fraction, and dP/dt max. Only bilateral sympathectomy rats had significant increases in ejection fraction (P <. 001) with dobutamine. Fibrotic tissue and matrix metalloproteinase expression decreased in the bilateral sympathectomy group compared to that in the myocardial infarction group (P <. 001) and was associated with left ventricular wall thickness maintenance and better apoptotic markers in noninfarcted myocardium. Conclusions: Bilateral sympathectomy effectively attenuated left ventricular remodeling and preserved systolic function after myocardial infarction induction in rats.
- Mesenteric hypoperfusion and inflammation induced by brain death are not affected by inhibition of the autonomic storm in rats(2015) SIMAS, Rafael; FERREIRA, Sueli G.; MENEGAT, Laura; ZANONI, Fernando L.; CORREIA, Cristiano J.; SILVA, Isaac A.; SANNOMIYA, Paulina; MOREIRA, Luiz F.P.OBJECTIVES: Brain death is typically followed by autonomic changes that lead to hemodynamic instability, which is likely associated with microcirculatory dysfunction and inflammation. We evaluated the role of the microcirculation in the hemodynamic and inflammatory events that occur after brain death and the effects of autonomic storm inhibition via thoracic epidural blockade on mesenteric microcirculatory changes and inflammatory responses. METHODS: Male Wistar rats were anesthetized and mechanically ventilated. Brain death was induced via intracranial balloon inflation. Bupivacaine (brain death-thoracic epidural blockade group) or saline (brain death group) infusion via an epidural catheter was initiated immediately before brain death induction. Sham-operated animals were used as controls (SH group). The mesenteric microcirculation was analyzed via intravital microscopy, and the expression of adhesion molecules was evaluated via immunohistochemistry 180 min after brain death induction. RESULTS: A significant difference in mean arterial pressure behavior was observed between the brain death-thoracic epidural blockade group and the other groups, indicating that the former group experienced autonomic storm inhibition. However, the proportion of perfused small vessels in the brain death-thoracic epidural blockade group was similar to or lower than that in the brain death and SH groups, respectively. The expression of intercellular adhesion molecule 1 was similar between the brain death-thoracic epidural blockade and brain death groups but was significantly lower in the SH group than in the other two groups. The number of migrating leukocytes in the perivascular tissue followed the same trend for all groups. CONCLUSIONS: Although thoracic epidural blockade effectively inhibited the autonomic storm, it did not affect mesenteric hypoperfusion or inflammation induced by brain death.
- Cardiac MicroRNA Expression Profile After Experimental Brain Death Is Associated With Myocardial Dysfunction and Can Be Modulated by Hypertonic Saline(2022) FERREIRA, Ludmila Rodrigues Pinto; CORREIA, Cristiano Jesus; ZANONI, Fernando Luiz; CARVALHO-SILVA, Ana Carolina; ZANIRATTO, Ricardo; CANDIDO, Darlan da Silva; ALMEIDA, Rafael Ribeiro; BREITHAUPT-FALOPPA, Ana Cristina; CUNHA-NETO, Edecio; MOREIRA, Luiz Felipe P.Background. Brain death (BD) is associated with systemic inflammatory compromise, which might affect the quality of the transplanted organs. This study investigated the expression profile of cardiac microRNAs (miRNAs) after BD, and their relationship with the observed decline in myocardial function and with the changes induced by hypertonic saline solution (HSS) treatment. Methods. Wistar rats were assigned to sham-operation (SHAM) or submitted to BD with and without the administration of HSS. Cardiac function was assessed for 6 h with left ventricular (LV) pressure-volume analysis. We screened 641 rodent miRNAs to identify differentially expressed miRNAs in the heart, and computational and functional analyses were performed to compare the differentially expressed miRNAs and find their putative targets and their related enriched canonical pathways. Results. An enhanced expression in canonical pathways related to inflammation and myocardial apoptosis was observed in BD induced group, with 2 miRNAs, miR-30a-3p, and miR-467f, correlating with the level of LV dysfunction observed after BD. Conversely, HSS treated after BD and SHAM groups showed similar enriched pathways related to the maintenance of heart homeostasis regulation, in agreement with the observation that both groups did not have significant changes in LV function. Conclusions. These findings highlight the potential of miRNAs as biomarkers for assessing damage in BD donor hearts and to monitor the changes induced by therapeutic measures like HSS, opening a perspective to improve graft quality and to better understand the pathophysiology of BD. The possible relation of BD-induced miRNA's on early and late cardiac allograft function must be investigated.
- Effects of sympathectomy on myocardium remodeling and function(2021) JORDAO, Mauricio Rodrigues; PESSOA, Fernanda G.; FONSECA, Keila C. B.; ZANONI, Fernando; SALEMI, Vera M. C.; SOUZA, Leandro E.; RIBEIRO, Orlando N.; FERNANDES, Fabio; IRIGOYEN, Maria Claudia; MOREIRA, Luiz Felipe P.; MADY, Charles; RAMIRES, Felix Jose AlvarezOBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.
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