Evaluation of the endothelial glycocalyx damage in the microcirculation alterations associated to the circulatory shock

• Grant number: 19/06187-1
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2019
• End date: October 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carlos Henrique Miranda
• Grantee: Carlos Henrique Miranda
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The endothelial glycocalyx is a layer consisting of a tangle of glycosaminoglycans adhered to membrane proteins that line the endothelial surface of the vessel. Some physiological functions have been indicated for this structure such as control of vascular permeability, participation in the adhesion of inflammatory and platelet cells, etc. Circulatory shock is a severe manifestation of different pathologies with high mortality. Microcirculation impairment appears to play a central role in the establishment and maintenance of shock contributing to poor tissue perfusion. Maintaining inadequate tissue perfusion leads to multiple organ dysfunctions. Endothelial glycocalyx impairment may have a major role in the establishment of microcirculatory dysfunction observed in the shock, such as, for example, contributing to the activation of coagulation and thrombosis of the microcirculation, reducing the gas exchange surface with the tissue, besides causing peridural edema which makes diffusion of oxygen to tissue difficult. Objective: To evaluate the role of endothelial glycocalyx injury in microcirculatory dysfunction establishment associated with circulatory shock. Methodology: Sixty patients with circulatory shock (20 with septic shock, 20 with hemorrhagic shock, 20 with cardiogenic/obstructive shock) will be included. Endothelial glycocalyx injury will be assessed by serum dosage of syndecan-1, glypican-3, aggrecan, and hyaluronic acid through commercial ELISA kits and sequential urinary dosage of glycosaminoglycan by DMMB assay. The evaluation of the microcirculation will be performed through sublingual capillaroscopic through Glycocheck® equipment (capillary density, length, diameter, the velocity of blood flow, thickness of glycocalyx layer). The following clinical outcomes will also be assessed: development of acute renal injury (through cystatin-C dosing); the need for renal replacement therapy (hemodialysis); multiple organ dysfunctions (SOFA score); disseminated intravascular coagulation (DIC score), general mortality that will be correlated with markers of endothelial glycocalyx injury. Significance: If our theory is confirmed, new therapeutic perspectives will be opened for the treatment of circulatory shock through the preservation/restoration of the endothelial glycocalyx. The acquired background will allow the realization of experimental and clinical studies using different strategies to restore endothelial glycocalyx, including the use of various natural polymers found abundantly in the Brazilian flora. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DO ESPIRITO SANTO, DOUGLAS ALEXANDRE; BERTOLDI LEMOS, ANNA CRISTINA; MIRANDA, CARLOS HENRIQUE. In vivo demonstration of microvascular thrombosis in severe COVID-19. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, AUG 2020. (19/06187-1)

DO ESPIRITO SANTO, DOUGLAS ALEXANDRE; BERTOLDI LEMOS, ANNA CRISTINA; MIRANDA, CARLOS HENRIQUE. In vivo demonstration of microvascular thrombosis in severe COVID-19. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, v. 50, n. 4, p. 5-pg., 2020-08-13. (19/06187-1)