Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis.

Abstract

RATIONALE:

Hyperchloremic acidosis is common in the critically ill and is often iatrogenic. We have previously shown that hyperchloremic acidosis increases nuclear factor-kappaB DNA binding in lipopolysaccharide-stimulated RAW 264.7 cells. However, evidence that hyperchloremic acidosis leads to increased inflammation in vivo has been limited to nitric oxide.

OBJECTIVES:

To determine if acidosis, induced by dilute hydrochloric acid (HCl) infusion, will increase circulating inflammatory mediator levels in an experimental model of severe sepsis in rats.

METHODS:

Eighteen hours after inducing lethal sepsis by cecal ligation and puncture in 20 adult, male, Sprague-Dawley rats, we randomized animals into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L, respectively. In group 1, we infused a similar volume of lactated Ringer solution. In all groups infusion continued 8 h or until the animal died.

MEASUREMENTS AND MAIN RESULTS:

We measured arterial blood gases, whole-blood lactate, and chloride, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 levels at 0 h, 4 h, and 8 h. All measured cytokines increased over time. Compared to group 1, animals in groups 2 and 3 exhibited greater increase in all three cytokines, with the greatest increases seen with severe acidosis.

CONCLUSION:

Moderate (SBE, - 5 to - 10) and severe (SBE, - 10 to - 15) acidosis, induced by HCl infusion, increases circulating levels of IL-6, IL-10, and TNF in normotensive septic rats.

• Authors: John A Kellum, Mingchen Song, Eyad Almasri
• Journal: Chest (Chest) Vol. 130 Issue 4 Pg. 962-7 (Oct 2006) ISSN: 0012-3692 [Print] United States
• PMID: 17035425 (Publication Type: Journal Article)

Chemical References

• Chlorides
• Inflammation Mediators
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Hydrochloric Acid

Topics

• Acid-Base Equilibrium (drug effects, immunology)
• Acidosis (chemically induced, immunology)
• Animals
• Blood Pressure
• Chlorides (blood)
• Enzyme-Linked Immunosorbent Assay
• Fluid Therapy
• Hydrochloric Acid
• Inflammation Mediators (blood)
• Interleukin-10 (blood)
• Interleukin-6 (blood)
• Male
• Rats
• Rats, Sprague-Dawley
• Shock, Septic (chemically induced, immunology)
• Tumor Necrosis Factor-alpha (metabolism)