Characterization of the microcirculation dysfunction kinetics in sepsis

• Grant number: 13/02265-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date until: June 01, 2013
• End date until: May 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ivan Hong Jun Koh
• Grantee: Bianca Cestari Zychar
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 11/20401-4 - Sepsis: integrating basic research and clinical research II, AP.TEM

Abstract

Sepsis is an important public health problem and its treatment have been mainly guided by macrohemodynamic parameters despite the current evidences showing that microcirculatory dysfunction occur earlier to macro-circulation changes, and their dysfunction has been intrinsically related with the genesis of Multiple Organ Dysfunction Syndrome. Thus, the study of the microcirculation dysfunction kinetics, of varying organs, in increasing stages of sepsis, appears to be a step to comprehend the microcirculatory dysfunction process in order to aid in the therapeutic management of severe sepsis and septic shock which still continues with unacceptably high mortality. Considering that inner lining of all microvessels is comprised by endothelial cells, the study of endothelial cells junction proteins as well as intracellular signaling pathways, both related to the integrity of the endothelial barrier, may have potential as monitor of the sepsis severity and serve as a therapeutic guide and prognosis. Thus, this study aimed to correlate biological markers related to endothelial dysfunction (PECAM-1, VE-Cadherin, protein signaling Rho GTPases and Src) of microvessels in sepsis in order to broaden the knowledge about these organ-specific molecular mechanisms expecting to generate new perspectives for the reduction of morbidity and mortality in sepsis.