Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia - PubMed (original) (raw)
Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia
Antje Pittner et al. Intensive Care Med. 2003 Feb.
Abstract
Objective: To determine the mechanisms of improved gut mucosal acidosis associated with selective inducible nitric oxide synthase (iNOS) inhibition.
Design: Prospective, controlled experimental study.
Setting: Animal research laboratory.
Animals: Fourteen domestic pigs.
Interventions: 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.
Measurements and 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.
Similar articles
- Effect of combining nicotinamide as a PARS-inhibitor with selective iNOS blockade during porcine endotoxemia.
Stehr A, Ploner F, Tugtekin I, Matejovic M, Theisen M, Zülke C, Georgieff M, Radermacher P, Jauch KW. Stehr A, et al. Intensive Care Med. 2003 Jun;29(6):995-1002. doi: 10.1007/s00134-003-1739-6. Epub 2003 May 9. Intensive Care Med. 2003. PMID: 12739012 - Increased ileal-mucosal-arterial PCO2 gap is associated with impaired villus microcirculation in endotoxic pigs.
Tugtekin IF, Radermacher P, Theisen M, Matejovic M, Stehr A, Ploner F, Matura K, Ince C, Georgieff M, Träger K. Tugtekin IF, et al. Intensive Care Med. 2001 Apr;27(4):757-66. doi: 10.1007/s001340100871. Intensive Care Med. 2001. PMID: 11398705 - Species-specific modulation of the nitric oxide pathway after acute experimentally induced endotoxemia.
Bachetti T, Pasini E, Suzuki H, Ferrari R. Bachetti T, et al. Crit Care Med. 2003 May;31(5):1509-14. doi: 10.1097/01.CCM.0000063269.35714.7E. Crit Care Med. 2003. PMID: 12771626 - Opening the microcirculation: can vasodilators be useful in sepsis?
Buwalda M, Ince C. Buwalda M, et al. Intensive Care Med. 2002 Sep;28(9):1208-17. doi: 10.1007/s00134-002-1407-2. Epub 2002 Jul 27. Intensive Care Med. 2002. PMID: 12209267 Review. - Techniques to assess tissue oxygenation in the clinical setting.
Sakr Y. Sakr Y. Transfus Apher Sci. 2010 Aug;43(1):79-94. doi: 10.1016/j.transci.2010.05.012. Epub 2010 Jun 17. Transfus Apher Sci. 2010. PMID: 20692624 Review.
Cited by
- Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study.
Dubin A, Murias G, Maskin B, Pozo MO, Sottile JP, Barán M, Edul VS, Canales HS, Badie JC, Etcheverry G, Estenssoro E. Dubin A, et al. Crit Care. 2005 Apr;9(2):R66-73. doi: 10.1186/cc3021. Epub 2005 Jan 11. Crit Care. 2005. PMID: 15774052 Free PMC article. - HMR1402, a potassium ATP channel blocker during hyperdynamic porcine endotoxemia: effects on hepato-splanchnic oxygen exchange and metabolism.
Asfar P, Iványi Z, Bracht H, Hauser B, Pittner A, Vassilev D, Nalos M, Leverve XM, Brückner UB, Radermacher P, Fröba G. Asfar P, et al. Intensive Care Med. 2004 May;30(5):957-64. doi: 10.1007/s00134-004-2258-9. Epub 2004 Mar 26. Intensive Care Med. 2004. PMID: 15045166 - Arginine and citrulline and the immune response in sepsis.
Wijnands KA, Castermans TM, Hommen MP, Meesters DM, Poeze M. Wijnands KA, et al. Nutrients. 2015 Feb 18;7(3):1426-63. doi: 10.3390/nu7031426. Nutrients. 2015. PMID: 25699985 Free PMC article. Review. - Artichoke, cynarin and cyanidin downregulate the expression of inducible nitric oxide synthase in human coronary smooth muscle cells.
Xia N, Pautz A, Wollscheid U, Reifenberg G, Förstermann U, Li H. Xia N, et al. Molecules. 2014 Mar 24;19(3):3654-68. doi: 10.3390/molecules19033654. Molecules. 2014. PMID: 24662080 Free PMC article. - A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.
Wang Z, Feng K, Yue M, Lu X, Zheng Q, Zhang H, Zhai Y, Li P, Yu L, Cai M, Zhang X, Kang X, Shi W, Xia X, Chen X, Cao P, Li Y, Chen H, Ling Y, Li Y, He F, Zhou G. Wang Z, et al. Hum Genet. 2013 Mar;132(3):337-46. doi: 10.1007/s00439-012-1253-4. Epub 2012 Nov 30. Hum Genet. 2013. PMID: 23192595
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous