Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia.
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.
Pittner
Antje
A
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Parkstrasse 11, 89073 Ulm, Germany.
Nalos
Marek
M
Asfar
Pierre
P
Yang
Yan
Y
Ince
Can
C
Georgieff
Michael
M
Brückner
Uwe Bernd
UB
Radermacher
Peter
P
Fröba
Gebhard
G
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
D000578:Amidines; D001596:Benzylamines; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II