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Laboratory and Animal InvestigationsEffects of Hyperchloremic Acidosis on Arterial Pressure and Circulating Inflammatory Molecules in Experimental Sepsis
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.
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Support for this project was provided, in part, by a grant from Abbott Laboratories and by the Laerdal Foundation for Acute Medicine.