title: Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis.
abstract: 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.
  
  
  METHODS
  Randomized, open-label, controlled experiment.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Twenty-four adult, male, Sprague-Dawley rats.
  
  
  METHODS
  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.
  
  
  METHODS
  We measured mean arterial pressure (MAP), arterial blood gases, electrolytes, plasma nitrate/nitrite, tumor necrosis factor (TNF)-alpha, 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(-) (R(2) = 0.50, p < 0.0001) and less well with the decrease in pH (R(2) = 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-alpha, IL-6, or IL-10 levels were not significantly different from control animals.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MANTRA Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Kellumja@ccm.upmc.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.forename: Mingchen
authors.initials: M
authors.lastname: Song
authors.forename: Ramesh
authors.initials: R
authors.lastname: Venkataraman
mesh_terms: D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D001794:Blood Pressure; D006851:Hydrochloric Acid / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D006851:Hydrochloric Acid