Autoregulation of blood flow drives early hypotension in a rat model of systemic inflammation induced by bacterial lipopolysaccharide

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Moretti, Eduardo H. ; Rodrigues, Abner C. ; Marques, Bruno V. ; Totola, Leonardo T. ; Ferreira, Caroline B. ; Brito, Camila F. ; Matos, Caroline M. ; da Silva, Filipe A. ; Santos, Robson A. S. ; Lopes, Luciana B. ; Moreira, Thiago S. ; Akamine, Eliana H. ; Baccala, Luiz A. ; Fujita, Andre ; Steiner, Alexandre A.

• Document type: Journal article
• Source: PNAS NEXUS; v. 2, n. 2, p. 13-pg., 2023-02-01.

Abstract

Uncontrolled vasodilation is known to account for hypotension in the advanced stages of sepsis and other systemic inflammatory conditions, but the mechanisms of hypotension in earlier stages of such conditions are not clear. By monitoring 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 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. Consistent with this hypothesis, an assessment of squared coherence and partial-directed coherence revealed that, at the onset of hypotension, the flow-pressure relationship was strengthened at frequencies (<0.2 Hz) known to be associated with autoregulation. The autoregulatory escape to phenylephrine-induced vasoconstriction, another proxy of autoregulation, was also strengthened in this phase. The competitive demand that drives prioritization of flow over pressure regulation could be edema-associated hypovolemia, as this became detectable at the onset of hypotension. Accordingly, blood transfusion aimed at preventing hypovolemia brought the autoregulation proxies back to normal and prevented the fall in vascular resistance. This novel hypothesis opens a new avenue of investigation into the mechanisms that can drive hypotension in systemic inflammation. (AU)

• FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 20/00631-4 - Development of hypothermia in systemic inflammation: the signaling hypothesis cryogenic
• Grantee: Caroline Martins de Matos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/03418-0 - Hypothermia in Sepsis: causes and consequences
• Grantee: Alexandre Alarcon Steiner
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/09399-7 - Development of hypothermia in systemic inflammation: the brain hypoxia hypothesis
• Grantee: Eduardo Hermogenes Moretti
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/21934-5 - Network statistics: theory, methods, and applications
• Grantee: André Fujita
• Support Opportunities: Research Projects - Thematic Grants