4.5 Article

Autonomic Disbalance During Systemic Inflammation is Associated with Oxidative Stress Changes in Sepsis Survivor Rats

Journal

INFLAMMATION
Volume 45, Issue 3, Pages 1239-1253

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-021-01617-6

Keywords

cecal ligation and puncture; blood pressure; septic shock; endotoxin

Funding

  1. Sao Paulo Research Foundation (FAPESP) [2016/17681-9]
  2. National Council for Scientific and Technological Development (CNPq), Brazil [2017/09878-0]

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Sepsis, characterized by a drop in blood pressure and high mortality rate, affects millions of people worldwide. Modern supportive care has improved survival, but complications can still occur. This study found that in rats, cecal ligation and puncture caused persistent cardiovascular dysfunctions, and sepsis survivors had altered cardiovascular responses to lipopolysaccharide. These findings suggest that oxidative stress may play a role in the cardiovascular regulation of sepsis survivors.
Sepsis affects 31.5 million people worldwide. It is characterized by an intense drop in blood pressure driving to cardiovascular morbidity and mortality. Modern supportive care has increased survival in patients; however, after experiencing sepsis, several complications are observed, which may be potentiated by new inflammatory events. Nevertheless, the interplay between sepsis survivors and a new immune challenge in cardiovascular regulation has not been previously defined. We hypothesized that cecal ligation and puncture (CLP) cause persistent cardiovascular dysfunctions in rats as well as changes in autonomic-induced cardiovascular responses to lipopolysaccharide (LPS). Male Wistar rats had mean arterial pressure (MAP) and heart rate (HR) recorded before and after LPS or saline administration to control or CLP survivor rats. CLP survivor rats had similar baseline MAP and HR when compared to control. LPS caused a drop in MAP accompanied by tachycardia in control, while CLP survivor rats had a noteworthy enhanced MAP and a blunted tachycardia. LPS-induced hemodynamic changes were related to an autonomic disbalance to the heart and resistance vessels that were expressed as an increased low- and high-frequency power of pulse interval in CLP survivors after saline and enhancement in the low-frequency power of systolic arterial pressure in control rats after LPS. LPS-induced plasma interferon gamma, but not interleukin-10 surges, was blunted in CLP survivor rats. To further access whether or not LPS-induced autonomic disbalance in CLP survivor rats was associated with oxidative stress dysregulation, superoxide dismutase (SOD) activity and thiobarbituric acid reactive substances (TBARS) plasma levels changes were measured. LPS-induced oxidative stress was higher in CLP survivor rats. These findings indicate that key changes in hemodynamic regulation of CLP survivors rats take place in response to LPS that are associated with oxidative stress changes, i.e., reduced SOD activity and increased TBARS levels.

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