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Laboratory and Animal Investigations |

Effects of Hyperchloremic Acidosis on Arterial Pressure and Circulating Inflammatory Molecules in Experimental Sepsis*

John A. Kellum; Mingchen Song; Ramesh Venkataraman
Author and Funding Information

*From the MANTRA Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Correspondence to: John A. Kellum, MD, FCCP, University of Pittsburgh School of Medicine, Department of Critical Care Medicine, 3550 Terrace St, Pittsburgh, PA 15261; e-mail: Kellumja@ccm.upmc.edu



Chest. 2004;125(1):243-248. doi:10.1378/chest.125.1.243
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Study objective: To determine the effects of hyperchloremic acidosis, induced by dilute HCl infusion, on BP and circulating inflammatory mediators in an experimental model of severe sepsis in the rat.

Design: Randomized, open-label, controlled experiment.

Setting: University research laboratory.

Participants: Twenty-four adult, male, Sprague-Dawley rats.

Intervention: Eighteen hours after inducing lethal sepsis by cecal ligation and puncture, animals were randomized and classified 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, infusions were continued for 8 h or until the animals died.

Measurements: We measured mean arterial pressure (MAP), arterial blood gases, electrolytes, plasma nitrate/nitrite, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels at 0 h, 3 h, 6 h, and 8 h.

Results: MAP remained stable in group 1 but decreased in groups 2 and 3 (p < 0.001), such that at 8 h MAP was much higher in group 1 (94 ± 9.2 mm Hg) [± SD] compared to either group 2 (71.6 ± 20.1 mm Hg) or group 3 (49.4 ± 33.2 mm Hg) [p = 0.01]. This change in MAP correlated with the increase in plasma Cl (R2 = 0.50, p < 0.0001) and less well with the decrease in pH (R2 = 0.24, p < 0.001). After 6 h of acidosis, plasma nitrite levels were significantly higher in group 2 animals compared to either group 1 or group 3 animals (p < 0.05). Plasma TNF-α, IL-6, or IL-10 levels were not significantly different from control animals.

Conclusion: Moderate acidosis (SBE of 5 to 10 mEq/L), induced by HCl infusion, worsened BP and increased plasma nitrate/nitrite levels but had no effect on circulating cytokines in septic rats. However, severe acidosis (SBE of 10 to 15 mEq/L), while still causing hypotension, did not affect plasma nitrate/nitrite levels.

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