FERNANDO LUIZ ZANONI
Projetos de Pesquisa
Unidades Organizacionais
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- 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.
- 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.
- Effect of bilateral sympathectomy in a rat model of dilated cardiomyopathy induced by doxorubicin(2020) SILVA, Raphael dos Santos Coutinho e; ZANONI, Fernando Luiz; SIMAS, Rafael; SILVA, Mateus Henrique Fernandes Martins da; ARMSTRONG JUNIOR, Roberto; CORREIA, Cristiano de Jesus; FALOPPA, Ana Cristina Breithaupt; MOREIRA, Luiz Felipe PinhoObjective: The study objective was to evaluate the effect of bilateral sympathectomy on ventricular remodeling and function in a rat model of dilated cardiomyopathy induced by doxorubicin. Methods: Dilated cardiomyopathy was induced in male Wistar rats by weekly intraperitoneal injection of doxorubicin (2 mg/kg) for 9 weeks. Animals were divided into 4 groups: dilated cardiomyopathy; bilateral sympathectomy, submitted on day 15 of the protocol to bilateral sympathectomy; angiotensin-converting enzyme inhibitor, treated with enalapril through day 15 until the end of the experimental protocol; and sham, nonsubmitted through doxorubicin protocol, with weekly intraperitoneal injections of saline solution (0.9%). The left ventricular function was assessed, and the heart was collected for posterior analyses. Results: The dilated cardiomyopathy group presented a significant decrease in the myocardial efficiency when compared with the sham group (33.4% vs 71.2%). Only the bilateral sympathectomy group was able to preserve it (57.5%; P = .0001). A significant dilatation in the left ventricular chamber was observed in the dilated cardiomyopathy group (15.9 mu m(2)) compared with the sham group (10.2 mu m(2); P = .0053). Sympathectomy and enalapril prevented ventricular remodeling (9.5 and 9.6 mu m(2), respectively; P = .0034). There was a significant increase in interstitial myocardial fibrosis in the dilated cardiomyopathy group (14.8%) when compared with the sham group (2.4%; P = .0001). This process was significantly reduced with sympathectomy and enalapril (8.7 and 3.9%, respectively; P = .0001). Conclusions: Bilateral sympathectomy was effective in preventing remodeling and left ventricular dysfunction in a rat model of dilated cardiomyopathy induced by doxorubicin.
- Evidence of bone marrow downregulation in brain-dead rats(2017) MENEGAT, Laura; SIMAS, Rafael; CALIMAN, Julia M.; ZANONI, Fernando L.; JACYSYN, Jacqueline F.; SILVA, Luiz Fernando F. da; BORELLI, Primavera; MOREIRA, Luiz Felipe P.; SANNOMIYA, PaulinaExperimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). This study aimed to investigate leucocyte behaviour in bone marrow and blood after BD in rats. BD was induced using intracranial balloon catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone marrow cells were harvested every six hours from the femoral cavity and used for total and differential counts. They were analysed further by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression and apoptosis/necrosis [ annexin V/propidium iodide (PI) protocol]. BD rats exhibited a reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, P = 0.1; CD4, P = 0.4; CD3/CD4, P = 0.4; CD5, P = 0.4, CD3/CD5, P = 0.2; CD8, P = 0.8). Expression of L-selectin and beta(2)-integrins on granulocytes did not differ (CD11a, P = 0.9; CD11b/c, P = 0.7; CD62L, P = 0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, P = 0.73; PI, P = 0.21; Annexin V/PI, P = 0.29). In conclusion, data presented suggest that the downregulation of the bone marrow is triggered by brain death itself, and it is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression or apoptosis and necrosis.