Chest
Volume 125, Issue 1, January 2004, Pages 243-248
Journal home page for Chest

Laboratory and Animal Investigations
Effects of Hyperchloremic Acidosis on Arterial Pressure and Circulating Inflammatory Molecules in Experimental Sepsis

https://doi.org/10.1378/chest.125.1.243Get rights and content

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.

Section snippets

Surgical Preparation

Following approval by the Animal Care and Use Committee of the University of Pittsburgh Medical Center, we anesthetized 24 adult, male, Sprague-Dawley rats with pentobarbital sodium (40 mg/kg intraperitoneal). We performed a midline laparotomy, exteriorized the cecum, and placed a ligature inferior to the ileocecal valve using 4–0 silk. We then punctured the cecum three times using a sterile 18-gauge needle, placing one puncture site on each of the three antimesenteric surfaces. We returned the

Results

Two animals died before completing the 8-h protocol, one in group 1 and the other in group 3; both died just prior to 7 h. We administered a mean volume of 0.1 N HCl of 10.2 mL to group 2 animals and 13.1 mL to group 3 animals; control animals received 9.1 mL of lactated Ringer solution (p = not significant).

Acid-base variables at each time point are summarized in Table 1. After 8 h, SBE was significantly lower in HCl-treated animals (− 10.0 ± 3.4 and − 18.8 ± 4.6 for groups 2 and 3,

Discussion

The primary finding of our study is that hyperchloremic acidosis, induced by HCl infusion, significantly reduced the MAP in normotensive, septic animals. Moderate acidosis (decrease in arterial SBE by 5 to 10 mEq/L) was associated with increased plasma nitrate/nitrite levels, but, surprisingly, more severe acidosis (decrease in arterial SBE by 10 to 15 mEq/L) was associated with changes in nitrate/nitrite levels in response to sepsis that closely resembled that of nonacidemic control animals.

Conclusion

Hyperchloremic metabolic acidosis worsens hemodynamic variables in this animal model of CLP-induced sepsis. The mechanism(s) responsible for hypotension in this setting are unclear. However, they are likely complex and may involve increased NO release when acidosis is moderate and other mechanisms when more severe.

ACKNOWLEDGMENT

The authors thank Jeff Schmigel, BS, for technical assistance.

References (35)

  • JH Waters et al.

    Dilutional acidosis following hetastarch or albumin in healthy volunteers

    Anesthesiology

    (2000)
  • FJ Liskaser et al.

    Role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass-associated acidosis

    Anesthesiology

    (2000)
  • M Rehm et al.

    Acid-base changes caused by 5% albumin versus 6% hydroxyethyl starch solution in patients undergoing acute normovolemic hemodilution: a randomized prospective study

    Anesthesiology

    (2000)
  • P Stewart

    Modern quantitative acid-base chemistry

    Can J Physiol Pharmacol

    (1983)
  • JA Kellum

    Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: improved survival and acid-base balance with a synthetic colloid in a balanced electrolyte solution compared to saline

    Crit Care Med

    (2002)
  • L Opie

    Effect of extracellular pH on function and metabolism of isolated perfused rat heart

    J Appl Physiol

    (1965)
  • D Cooper et al.

    Bicarbonate does not increase left ventricular contractility during L-lactic acidemia in pigs

    Am Rev Respir Dis

    (1993)
  • Cited by (0)

    Support for this project was provided, in part, by a grant from Abbott Laboratories and by the Laerdal Foundation for Acute Medicine.

    View full text