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Regional arterial hemodynamics study and its correlation with macro and microcirculation in different stages of sepsis in rats

Grant number: 17/25189-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2018
Effective date (End): February 28, 2019
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Ivan Hong Jun Koh
Grantee:Marta Naomi Nakamae
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Sepsis is a complex disease resulting from the multifaceted response of the host to a pathogen, causing multiple organ dysfunction. Its incidence is increasing, being today responsible for 25% of bed occupations in Brazil in ICUs. Sepsis is the main cause of mortality in the ICU, reaching a rate of 55.7% in Brazil and 30-40% in the world, surpassing deaths due to myocardial infarction and cancer. The magnitude of the problem shows the need for improvements in therapeutics, which, however, has not achieved great progress for decades, thus denoting the need for further studies on its pathophysiology. Although current evidence shows that microcirculatory dysfunction precedes macrohemodynamic changes, current therapy is based on macrocirculatory dynamics due to the lack of instrumentation to monitor microhemodynamics in the clinic. In this context, little is known about the circulation changes located between the macro and microcirculation in sepsis, named regional circulation, whose dysfunction can precede macrocirculation events and provide the anticipation of a therapeutic moment, minimizing the evolution to organ dysfunction. Objective: To study the hemodynamics of the regional arterial circulation in sepsis and to correlate with macro and microcirculation. Methods: Twenty female wistar rats (n = 20), aged 3 to 4 months, weighing 200g to 300g, under general anesthesia with isoflurane during all procedures, distributed in 3 groups: Naive Group (n = 4) ), in order to obtain basal animal data (T = 0h); Control group (n = 8), submitted to intravenous infusion of saline and Sepsis Group (n = 8), submitted to intravenous sepsis of 10 to 8 CFU / ml. The Control and Sepsis groups will be divided into 2 subgroups (n = 4 / subgroup): T = 3h and T = 6h monitoring (time schedules from the infusion of the bacteria or the vehicle timing). The flow of the regional arterial circulation (renal and superior mesenteric arteries and celiac trunk) will be evaluated by Transonic System Inc. TS420 transit-time perivascular flowmeter and compared to macrohemodynamic parameters (abdominal aorta flow, heart rate and mean arterial pressure), in addition , there will be a correlation with microhemodynamic parameters by the BLF 21 laser doppler flow meter (kidney, liver and terminal ileum's tissue perfusion unity) and microcirculatory evaluation of the same organs by the Sidestream Dark Field Imaging in the determined periods, whose images will be processed by the program AVA 3.0. At the end of the monitoring, the animals will be sacrificed under general anesthesia. (AU)

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