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Related Experiment Videos

Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis.

John A Kellum1, Mingchen Song, Eyad Almasri

  • 1University of Pittsburgh, School of Medicine, Department of Critical Care Medicine, 3550 Terrace St, Pittsburgh, PA 15261, USA. Kellumja@ccm.upmc.edu

Chest
|October 13, 2006
PubMed
Summary

Hyperchloremic acidosis in septic rats significantly increased inflammatory cytokines like IL-6, IL-10, and TNF. This suggests acidosis exacerbates inflammation during severe sepsis.

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Area of Science:

  • Critical care medicine
  • Sepsis research
  • Acid-base balance

Background:

  • Hyperchloremic acidosis is prevalent in critically ill patients, often iatrogenic.
  • Previous studies linked hyperchloremic acidosis to increased nuclear factor-kappaB DNA binding in vitro.
  • In vivo evidence for acidosis-induced inflammation was limited to nitric oxide.

Purpose of the Study:

  • To investigate if induced acidosis increases circulating inflammatory mediators in a rat model of severe sepsis.
  • To determine the impact of hydrochloric acid (HCl) infusion on inflammatory markers in sepsis.

Main Methods:

  • Sepsis was induced in rats via cecal ligation and puncture.
  • Animals were randomized into three groups: control (lactated Ringer infusion) and two acidosis groups (HCl infusion to achieve different base excess levels).

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  • Arterial blood gases, lactate, chloride, and cytokine levels (TNF, IL-6, IL-10) were measured over 8 hours.

    • Main Results:

    • All measured cytokines (TNF, IL-6, IL-10) increased over time in all groups.
    • Acidosis groups showed significantly greater increases in all three cytokines compared to the control group.
    • The most severe acidosis levels correlated with the largest increases in cytokine levels.

    Conclusions:

    • Moderate and severe acidosis, induced by HCl, elevates circulating IL-6, IL-10, and TNF levels in septic rats.
    • These findings indicate that acidosis exacerbates the inflammatory response in sepsis.
    • Acidosis may be a significant contributor to inflammation in critically ill septic patients.