Arterial tonus in septic shock: a new facet to an old problem.

• Grant number: 16/04921-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2016
• End date: September 30, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Alexandre Alarcon Steiner
• Grantee: Alexandre Alarcon Steiner
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: André Fujita ; Francisco Garcia Soriano ; Thiago dos Santos Moreira
• Associated scholarship(s): 18/00849-0 - Hemodynamic evaluation in non-anesthetized rats, BP.TT

Abstract

Septic shock is seen as a condition in which decreases in systemic vascular resistance (SVR) compromise tissue perfusion pressure. In this project, unexpected preliminary results have led us to question the applicability of this model to the most terminal phase of septic shock. We hypothesize that this terminal phase is associated with a switch in hemodynamic profile, with SVR transitioning from reduced to increased in a sudden and decompensated manner. We also propose that this increase in SVR is terminal for triggering a vicious cycle that drives the cardiac output (CO) downward to an extent that compromises tissue perfusion. This hypothesis will be tested in two rat models of shock induced by systemic inflammation: an aseptic model of endotoxemia and a septic model of E. coli peritonitis. Initial experiments will aim to confirm the reproducibility of the phenomenon in the endotoxic shock model, as well as the persistence of the terminal increase in SVR when volume expansion is used to favor a hyperdynamic state. We will then verify whether the same phenomenon occurs in the septic shock model. The Granger causality test will be employed to examine whether a vicious cycle involving SVR and CO exists in the terminal stages of shock. In a separate set of experiments, we will investigate if vasodilators capable of reversing the terminal rise in SVR can reduce mortality in endotoxic or septic shock. Electrophysiological measurements will also be made in order to determine whether a change in the gain of baroreceptors could be a trigger for the terminal rise in SVR. Lastly, to strengthen the translational aspect of the project, a systematic analysis of clinical data will be performed to probe for terminal rises in SVR in patients with septic shock. (AU)

Scientific publications

(8)

(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)

BARROS, MICHELE S.; LARA, PRISCILA G.; FONSECA, MONIQUE T.; MORETTI, EDUARDO H.; FILGUEIRAS, LUCIANO R.; MARTINS, JOILSON O.; CAPURRO, MARGARETH L.; STEINER, ALEXANDRE A.; SA-NUNES, ANDERSON. Aedes aegypti saliva impairs M1-associated proinflammatory phenotype without promoting or affecting M2 polarization of murine macrophages. PARASITES & VECTORS, v. 12, MAY 16 2019. (16/04921-1, 13/12467-0, 15/22934-0, 17/11540-7)

KOMEGAE, EVILIN N.; FONSECA, MONIQUE T.; CRUZ-MACHADO, SANSERAY DA SILVEIRA; TURATO, WALTER M.; FILGUEIRAS, LUCIANO R.; MARKUS, REGINA P.; STEINER, ALEXANDRE A.. Site-Specific Reprogramming of Macrophage Responsiveness to Bacterial Lipopolysaccharide in Obesity. FRONTIERS IN IMMUNOLOGY, v. 10, JUN 28 2019. (12/03831-8, 18/03418-0, 14/03719-9, 13/13691-1, 15/04557-5, 16/04921-1, 17/13350-0, 14/17407-9)

FONSECA, MONIQUE T.; MORETTI, EDUARDO H.; MARQUES, LUCAS M. M.; MACHADO, BIANCA F.; BRITO, CAMILA F.; GUEDES, JADY T.; KOMEGAE, EVILIN N.; VIEIRA, THAYNA S.; FESTUCCIA, WILLIAM T.; LOPES, NORBERTO P.; et al. A leukotriene-dependent spleen-liver axis drives TNF production in systemic inflammation. SCIENCE SIGNALING, v. 14, n. 679, p. 12-pg., 2021-04-20. (18/00849-0, 16/23540-9, 17/13350-0, 16/04921-1, 18/03418-0, 15/19530-5, 14/03719-9, 20/09399-7, 17/17403-1, 14/50265-3)

STEINER, ALEXANDRE A.. Should we let fever run its course in the early stages of COVID-19?. JOURNAL OF THE ROYAL SOCIETY OF MEDICINE, v. 113, n. 10, p. 3-pg., 2020-09-15. (18/03418-0, 12/03831-8, 16/04921-1)

FONSECA, MONIQUE T.; MORETTI, EDUARDO H.; MARQUES, LUCAS M. M.; MACHADO, BIANCA F.; BRITO, CAMILA F.; GUEDES, JADY T.; KOMEGAE, EVILIN N.; VIEIRA, THAYNA S.; FESTUCCIA, WILLIAM T.; LOPES, NORBERTO P.; et al. A leukotriene-dependent spleen-liver axis drives TNF production in systemic inflammation. Science Signaling, v. 14, n. 679, APR 20 2021. (16/23540-9, 18/03418-0, 17/17403-1, 17/13350-0, 15/19530-5, 16/04921-1, 20/09399-7, 14/50265-3, 14/03719-9, 18/00849-0)

STEINER, ALEXANDRE A.; ROMANOVSKY, ANDREJ A.. Energy Trade-offs in Host Defense: Immunology Meets Physiology. TRENDS IN ENDOCRINOLOGY AND METABOLISM, v. 30, n. 12, p. 4-pg., 2019-12-01. (18/03418-0, 12/03831-8, 16/04921-1)

FLATOW, ELIZABETH A.; KOMEGAE, EVILIN N.; FONSECA, MONIQUE T.; BRITO, CAMILA F.; MUSTEATA, FLORIN M.; ANTUNES-RODRIGUES, JOSE; STEINER, ALEXANDRE A.. Elucidating the role of leptin in systemic inflammation: a study targeting physiological leptin levels in rats and their macrophages. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 313, n. 5, p. R572-R582, NOV 2017. (16/04921-1, 13/09799-1, 14/03719-9, 12/03831-8)

STEINER, ALEXANDRE A.; FLATOW, ELIZABETH A.; BRITO, CAMILA F.; FONSECA, MONIQUE T.; KOMEGAE, EVILIN N.. Respiratory gas exchange as a new aid to monitor acidosis in endotoxemic rats: relationship to metabolic fuel substrates and thermometabolic responses. PHYSIOLOGICAL REPORTS, v. 5, n. 1, JAN 2017. (16/04921-1, 14/03719-9, 12/03831-8)