FERNANDO LUIZ ZANONI
Projetos de Pesquisa
Unidades Organizacionais
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- 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 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.
conferenceObject PULMONARY MICROCIRCULATION INTRAVITAL MICROSCOPIC STUDY: THE IMPACT OF BRAIN DEATH INDUCTION IN RATS.(2015) SIMAS, Rafael; ZANONI, Fernando L.; SILVA, Raphael C.; MENEGAT, Laura; SILVA, Isaac A.; SANNOMIYA, Paulina; MOREIRA, Luiz F.conferenceObject PULMONARY MICROCIRCULATION COMPROMISE AFTER BRAIN-DEAD INDUCTION IN RATS: AN INTRAVITAL MICROSCOPY STUDY(2015) SIMAS, Rafael; ZANONI, Fernando Luiz; MENEGAT, Laura; SANNOMIYA, Paulina; MOREIRA, Luiz Felipe- Thoracic bilateral sympathectomy attenuates oxidative stress and prevents ventricular remodelling in experimental pulmonary hypertension(2022) SILVA, Raphael dos Santos Coutinho e; WIGGENHAUSER, Lucas Moritz; SIMAS, Rafael; ZANONI, Fernando Luiz; MEDEIROS, Geisla; SILVA, Fernanda Beatriz da; OGATA, Daniel Cury; BREITHAUPT-FALOPPA, Ana Cristina; KRENNING, Guido; MOREIRA, Luiz Felipe PinhoOBJECTIVES: Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease that affects the pulmonary vasculature, leading to increased afterload and eventually right ventricular (RV) remodelling and failure. Bilateral sympathectomy (BS) has shown promising results in dampening cardiac remodelling and dysfunction in several heart failure models. In the present study, we investigated whether BS reduces pulmonary arterial remodelling and mitigates RV remodelling and failure. METHODS: PAH was induced in male Wistar rats by intraperitoneal injection of monocrotaline. Rats were divided into 3 groups, involving untreated PAH (n = 15), BS-treated PAH (n = 13) and non-manipulated control rats (n = 13). Three weeks after PAH induction, the rats were anaesthetized and RV function was assessed via the pressure-volume loop catheter approach. Upon completion of the experiment, the lungs and heart were harvested for further analyses. RESULTS: BS was found to prevent pulmonary artery remodelling, with a clear reduction in alpha-smooth muscle actin and endothelin-1 expression. RV end-systolic pressure was reduced in the BS group, and preload recruitable stroke work was preserved. BS, therefore, mitigated RV remodelling and cardiomyocyte hypertrophy and diminished oxidative stress. CONCLUSIONS: We showed that thoracic BS may be an important treatment option for PAH patients. Blockade of the sympathetic pathway can prevent pulmonary remodelling and protect the RV from oxidative stress, myocardial remodelling and function decay. Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease that affects both the pulmonary vasculature and the right ventricle (RV).
conferenceObject EFFECTS OF HYPERTONIC SALINE SOLUTION ON CARDIAC AND PULMONARY CHANGES AFTER BRAIN DEATH: AN EXPERIMENTAL STUDY(2017) CORREIA, Cristiano; MAGGALHAES, Daniel M.; ZANONI, Fernando; SIMAS, Rafael; SOARES, Rafaela Garcia Ferreira; SILVA, Raphael S. Coutinho E; BREITHAUPT-FALOPPA, Ana Cristina; SANNOMIYA, Paulina; MOREIRA, Luiz Felipe- Hypertonic Saline Modulates Heart Function and Myocardial Inflammatory Alterations in Brain-Dead Rats(2019) MAGALHAES, Daniel Marcelo S.; ZANONI, Fernando Luiz; CORREIA, Cristiano Jesus; SIMAS, Rafael; SOARES, Rafaela Garcia F.; SANNOMIYA, Paulina; MOREIRA, Luiz Felipe P.Background: Brain death (BD) in potential organ donors is responsible for hemodynamic instability and organ hypoperfusion, leading to myocardial dysfunction. Hypertonic saline (HS) is a volume expander with positive effects on hemodynamics and immunomodulation and was tested in this study to prevent left ventricular (LV) dysfunction and myocardial injury. Methods: BD was induced in anesthetized Wistar rats by inflating a subdural balloon catheter, except in sham-operated animals (n = 6). After BD induction, Control animals received only normal saline solution (NaCl 0.9%, 4 mL/kg; n = 6), and treated animals were divided to receive HS (NaCl, 7.5% 4 mL/kg) at 1 min (HS1, n = 6) or 60 min (HS60, n = 6) thereafter. We continuously assessed cardiac function for 6 h with LV pressure-volume analysis. Inflammatory response, markers of myocardial injury, and cellular apoptosis -related proteins were investigated. Results: BD was associated with decreased LV systolic and diastolic function. In comparison with the Control group, HS treatments improved LV ejection fraction (HS1, 51% [40-66]; HS60, 71% [28-82]; Control, 46% [23-55]; P < 0.05) and other parameters of LV systolic function 6 h after BD induction. However, no ventricular relaxation advantages were observed during the same period. HS treatments increased antiapoptotic protein expression and decreased vascular adhesion molecule and tumor necrosis factor alpha expression. No significant differences in histologic or structural protein changes were observed between groups. Conclusions: The observed data suggest that HS ameliorates LV systolic dysfunction and seems to reduce myocardial tissue compromise in BD rats, even when the treatment is performed during the process triggered by this event.
- Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study(2012) SIMAS, Rafael; SANNOMIYA, Paulina; CRUZ, Jose Walber M. C.; CORREIA, Cristiano de Jesus; ZANONI, Fernando Luiz; KASE, Mauricio; MENEGAT, Laura; SILVA, Isaac Azevedo; MOREIRA, Luiz Felipe P.OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of P-selectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage.