Study of thrombolytic treatment in microcirculatory changes caused by brain death

• Grant number: 21/02583-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2021
• End date: July 31, 2022
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Luiz Felipe Pinho Moreira
• Grantee: Caio Medeiros Fernandes
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Because of the advances in surgery knowledge, organs transplants became a possibility for treating patients with final-stage diseases. However, the lack of available organs is still an obstacle to these procedures. The majority of organs used in transplant are from brain death (BD), which has a considerable impact on its viability, according to clinical and experimental evidence, so it is important to consider the state of the donor in the results of the transplant. Thus, BD provokes alterations in microcirculation and inflammation, compromising the quality of the organ. First of all, the microcirculatory integrity, which is essential to guarantee adequate tissue oxygenation, is lose, so that, in previous studies of our laboratory, flow changes e microthrombi formation harmed the perfusion and so the viability of the organ. In order to improve the microcirculation, thrombolytic treatments are succeeding in cases of pulmonary embolism and ischemic stroke, causing the lysis of the clot and reestablishing the flow. In addition, beyond the microcirculation damage, the BD results in a systemic inflammatory process characterized by the higher expression of inflammatory mediators in the organs and hormonal changes secondary related to hypophysis failure, resulting in a reduction of the blood concentration of endogenous corticosterone, which intensifies organ degeneration. Having this in mind, the hormonal reposition of the donor with corticoids improves the quality of multiple organs for transplants. Based on the idea that controlling these changes can optimize the viability of the transplanted organ, this project has the purpose of investigating the effect of the treatment with tissue recombined plasminogen activator (rt-PA) and its association with metal-prednisolone in inflammation and microcirculation. Using a brain death rats model, the laboratory analysis will look for protein expression of NO synthases in mesentery, hemodynamic and gasometric changes, and dosage of corticosterone and inflammatory mediators.(AU)