title: Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia.
abstract: OBJECTIVE
  To determine the mechanisms of improved gut mucosal acidosis associated with selective inducible nitric oxide synthase (iNOS) inhibition.
  
  
  METHODS
  Prospective, controlled experimental study.
  
  
  METHODS
  Animal research laboratory.
  
  
  METHODS
  Fourteen domestic pigs.
  
  
  METHODS
  Anesthetized and mechanically ventilated pigs received continuous i.v. endotoxin for 24 h. A selective iNOS-inhibitor (1400 W, n=8) or vehicle (control, n=6) was started at 12 h of endotoxin and infused until the end of the experiment.
  
  
  RESULTS
  Before as well as at 12 and 24 h of endotoxin, portal venous flow (ultrasound probe), intestinal oxygen (O(2)) extraction, portal venous-arterial carbon dioxide (CO(2)) content difference and ileal mucosal-arterial PCO(2) gap (fiberoptic sensor) were assessed together with video recordings of the villous microcirculation (number of perfused/unperfused villi) using orthogonal polarization spectral imaging via an ileostomy. The gut wall microvascular blood flow (units) and hemoglobin O(2) saturation ( micro Hb-O(2)) were assessed with a combined laser Doppler flow and remission spectrophotometry probe. 1400 W blunted the otherwise progressive rise in the PCO(2) gap without affecting portal venous flow, regional O(2) and CO(2) exchange or the number of unperfused villi. While endotoxin markedly aggravated the heterogeneity of the microvascular blood flow and oxygenation, 1400 W had no further effect.
  
  
  CONCLUSIONS
  Given the uninfluenced parameters of the ileal mucosal microcirculation in our model of long-term porcine endotoxemia, selective iNOS inhibition probably improved the PCO(2) gap due to a redistribution of the microvascular perfusion within the gut wall and/or an amelioration of the cellular respiration.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Parkstrasse 11, 89073 Ulm, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Pittner
authors.forename: Marek
authors.initials: M
authors.lastname: Nalos
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Can
authors.initials: C
authors.lastname: Ince
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.forename: Uwe Bernd
authors.initials: UB
authors.lastname: Brückner
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Gebhard
authors.initials: G
authors.lastname: Fröba
mesh_terms: D000138:Acidosis / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D000578:Amidines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000150:complications* / Q000201:enzymology*; D006439:Hemodynamics / Q000187:drug effects; D007082:Ileum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D011446:Prospective Studies; D011897:Random Allocation; D013053:Spectrophotometry; D013552:Swine
chemical_list: D000578:Amidines; D001596:Benzylamines; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II