Tissue autoregulation as a mechanism of hypotension in the initial stage of septic shock

• Grant number: 24/01188-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2024
• End date: May 31, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Alexandre Alarcon Steiner
• Grantee: Deymisson Damitene Martins Feitosa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

By monitoring systemic hemodynamics with the highest temporal resolution in unanesthetized rats, in combination with ex-vivo assessment of vascular function, we found that early development of hypotension following injection of bacterial lipopolysaccharide (LPS) is brought about by a fall in vascular resistance when arterioles are still fully responsive to vasoactive agents. This approach further uncovered that the early development of hypotension stabilized blood flow. We thus hypothesized that prioritization of the local mechanisms of blood flow regulation (tissue autoregulation) over the brain-driven mechanisms of pressure regulation (baroreflex) underscored the early development of hypotension in this model. The next logical step is to test this hypothesis in animal models of systemic inflammation induced by live bacteria. The animal models employed will be cecal ligation and perforation (CLP), which is clinically relevant for modeling a polymicrobial sepsis of peritoneal origin, and a model of monomicrobial septic peritonitis caused by Escherichia coli, previously standardized in our laboratory. The hemodynamic profile will be monitored, seeking for evidence that blood flow is stabilized in the earliest phase of hypotension. the strength of autoregulation: (1) coherence of spontaneous fluctuations in blood flow and pressure below 0.2 Hz; and (2) autoregulatory escape from vasoconstrictors. We will also test the premise that a drop in blood volume (caused by increased capillary permeability) is the competitive demand that drives the prioritization of blood flow autoregulation and the consequent development of hypotension early in the CLP model and monomicrobial septic peritonitis.