Intestinal ischemia/reperfusion injury: defining the role of the gut microbiome

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Parks DA, Granger DN: Ischemia–reperfusion injury: a radical view. Hepatology8,680–682 (1988).
  Medline CASGoogle Scholar
• 2  Simpson R, Alon R, Kobzik L, Valeri CR, Shepro D, Hechtman HB: Neutrophil and non neutrophil-mediated injury in intestinal ischemia-reperfusion. Ann. Surg.218,444–453; discussion 453–454 (1993).
  Medline CASGoogle Scholar
• 3  Andersson B, Nilsson J, Brandt J, Hoglund P, Andersson R: Gastrointestinal complications after cardiac surgery. Br. J. Surg.92,326–333 (2005).
  Medline CASGoogle Scholar
• 4  Bjorck M, Bergqvist D, Troeng T, Haglund U, Hedberg B: Intestinal ischemia after abdominal aorta surgery. A dreaded complication surveyed by a combination of different methods. Lakartidningen96,3659–3662 (1999).
  Medline CASGoogle Scholar
• 5  Horton JW: Bacterial translocation after burn injury: the contribution of ischemia and permeability changes. Shock1,286–290 (1994).
  Medline CASGoogle Scholar
• 6  Haglund U: Gut ischaemia. Gut35,S73–S76 (1994).▪ Provides an excellent overview of the pathogenesis of intestinal ischemia/reperfusion (I/R) injury, and sets the condition within a clinical context.
  Medline CASGoogle Scholar
• 7  Kurland B, Brandt LJ, Delany HM: Diagnostic tests for intestinal ischemia. Surg. Clin. North Am.72,85–105 (1992).
  Medline CASGoogle Scholar
• 8  Park WM, Gloviczki P, Cherry KJ Jr et al.: Contemporary management of acute mesenteric ischemia: factors associated with survival. J. Vasc. Surg.35,445–452 (2002).
  MedlineGoogle Scholar
• 9  Yasuhara H, Niwa H, Takenoue T, Naka S: Factors influencing mortality of acute intestinal infarction associated with SIRS. Hepatogastroenterology52,1474–1478 (2005).
  MedlineGoogle Scholar
• 10  Alverdy JC, Laughlin RS, Wu L: Influence of the critically ill state on host–pathogen interactions within the intestine: gut-derived sepsis redefined. Crit. Care Med.31,598–607 (2003).▪ Alverdy challenged traditionally held views on the role of the gut flora, and clearly highlights numerous mechanisms by which the intestinal flora may interact with the host to detrimentally effect the outcome of seriously unwell patients.
  MedlineGoogle Scholar
• 11  Lederberg J: Infectious history. Science288,287–293 (2000).▪▪ The concepts outlined in this paper underpin much of the theory of systems biology and the need for metabonomic analysis of mammalian systems.
  Medline CASGoogle Scholar
• 12  Dethlefsen L, McFall-Ngai M, Relman DA: An ecological and evolutionary perspective on human–microbe mutualism and disease. Nature449,811–818 (2007).
  Medline CASGoogle Scholar
• 13  Nicholson JK, Lindon JC, Holmes E: ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica29,1181–1189 (1999).▪▪ Provides a definitive overview of metabonomic technology and why its application to human health provides significant potential.
  Medline CASGoogle Scholar
• 14  Nicholson JK, Connelly J, Lindon JC, Holmes E: Metabonomics: a platform for studying drug toxicity and gene function. Nat. Rev. Drug Discov.1,153–161 (2002).
  Medline CASGoogle Scholar
• 15  Dumas ME, Maibaum EC, Teague C et al.: Assessment of analytical reproducibility of ¹H NMR spectroscopy based metabonomics for large-scale epidemiological research: the INTERMAP Study. Anal. Chem.78,2199–2208 (2006).
  Medline CASGoogle Scholar
• 16  Brindle JT, Antti H, Holmes E et al.: Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using ¹H-NMR-based metabonomics. Nat. Med.8,1439–1444 (2002).
  Medline CASGoogle Scholar
• 17  Marchesi JR, Holmes E, Khan F et al.: Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. J. Proteome Res.6,546–551 (2007).
  Medline CASGoogle Scholar
• 18  Kruglyak L: The road to genome-wide association studies. Nat. Rev. Genet.9,314–318 (2008).
  Medline CASGoogle Scholar
• 19  Holmes E, Loo RL, Stamler J et al.: Human metabolic phenotype diversity and its association with diet and blood pressure. Nature453,396–400 (2008).▪▪ Describes how metabonomic technologies can be applied to large-scale populations, and the theory behind the metabonome-wide analysis. Also describes how gut flora may influence previously unassociated diseases such as hypertension.
  Medline CASGoogle Scholar
• 20  Kell DB: Metabolomics and systems biology: making sense of the soup. Curr. Opin Microbiol.7,296–307 (2004).▪ Provides a definitive outline of the current problems faced by systems biology.
  Medline CASGoogle Scholar
• 21  Kitano H: Computational systems biology. Nature420,206–210 (2002).▪▪ Kitano is credited as one of the fathers of systems biology, and this paper outlines the key principles on which it is based.
  Medline CASGoogle Scholar
• 22  Zelena E, Dunn WB, Broadhurst D et al.: Development of a robust and repeatable UPLC-MS method for the long-term metabolomic study of human serum. Anal. Chem.81,1357–1364 (2009).
  Medline CASGoogle Scholar
• 23  Rezzi S, Vera FA, Martin FP, Wang S, Lawler D, Kochhar S: Automated SPE-RP-HPLC fractionation of biofluids combined to off-line NMR spectroscopy for biomarker identification in metabonomics. J. Chromatogr. B Anal. Technol. Biomed. Life Sci.871,271–278 (2008).
  CASGoogle Scholar
• 24  Guy PA, Tavazzi I, Bruce SJ, Ramadan Z, Kochhar S: Global metabolic profiling analysis on human urine by UPLC-TOFMS: issues and method validation in nutritional metabolomics. J. Chromatogr. B Anal. Technol. Biomed. Life Sci.871,253–260 (2008).▪ Contempory review outlines how other spectroscopic techniques such as ultra-performance liquid chromatography may be effectively applied to metabonomics within a nutritional setting.
  CASGoogle Scholar
• 25  Deitch EA: Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings? Surgery131,241–244 (2002).
  MedlineGoogle Scholar
• 26  Koury J, Deitch EA, Homma H et al.: Persistent HIF-1a activation in gut ischemia/reperfusion injury: potential role of bacteria and lipopolysaccharide. Shock22,270–277 (2004).
  Medline CASGoogle Scholar
• 27  Chen LW, Egan L, Li ZW, Greten FR, Kagnoff MF, Karin M: The two faces of IKK and NF-κB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia–reperfusion. Nat. Med.9,575–581 (2003).
  Medline CASGoogle Scholar
• 28  Adams CA Jr, Sambol JT, Xu DZ, Lu Q, Granger DN, Deitch EA: Hemorrhagic shock induced upregulation of P-selectin expression is mediated by factors in mesenteric lymph and blunted by mesenteric lymph duct interruption. J. Trauma51,625–631; discussion 631–632 (2001).
  MedlineGoogle Scholar
• 29  Adams JM, Hauser CJ, Adams CA Jr, Xu DZ, Livingston DH, Deitch EA: Entry of gut lymph into the circulation primes rat neutrophil respiratory burst in hemorrhagic shock. Crit. Care Med.29,2194–2198 (2001).
  Medline CASGoogle Scholar
• 30  Caruso JM, Feketeova E, Dayal SD, Hauser CJ, Deitch EA: Factors in intestinal lymph after shock increase neutrophil adhesion molecule expression and pulmonary leukosequestration. J. Trauma55,727–733 (2003).
  Medline CASGoogle Scholar
• 31  Magnotti LJ, Upperman JS, Xu DZ, Lu Q, Deitch EA: Gut-derived mesenteric lymph but not portal blood increases endothelial cell permeability and promotes lung injury after hemorrhagic shock. Ann. Surg.228,518–527 (1998).
  Medline CASGoogle Scholar
• 32  Reddy BS, MacFie J, Gatt M, Macfarlane-Smith L, Bitzopoulou K, Snelling AM: Commensal bacteria do translocate across the intestinal barrier in surgical patients. Clin. Nutr.26,208–215 (2007).
  Medline CASGoogle Scholar
• 33  MacFie J, Reddy BS, Gatt M, Jain PK, Sowdi R, Mitchell CJ: Bacterial translocation studied in 927 patients over 13 years. Br. J. Surg.93,87–93 (2006).
  Medline CASGoogle Scholar
• 34  Cavriani G, Domingos HV, Oliveira-Filho RM, Sudo-Hayashi LS, Vargaftig BB, de Lima WT: Lymphatic thoracic duct ligation modulates the serum levels of IL-1β and IL-10 after intestinal ischemia/reperfusion in rats with the involvement of tumor necrosis factor α and nitric oxide. Shock27,209–213 (2007).
  Medline CASGoogle Scholar
• 35  Zimmerman BJ, Granger DN: Mechanisms of reperfusion injury. Am. J. Med. Sci.307,284–292 (1994).
  Medline CASGoogle Scholar
• 36  Granger DN, Hollwarth ME, Parks DA: Ischemia–reperfusion injury: role of oxygen-derived free radicals. Acta Physiol. Scand. Suppl.548,47–63 (1986).
  Medline CASGoogle Scholar
• 37  Horton JW, Walker PB: Oxygen radicals, lipid peroxidation, and permeability changes after intestinal ischemia and reperfusion. J. Appl. Physiol.74,1515–1520 (1993).
  Medline CASGoogle Scholar
• 38  Zimmerman BJ, Granger DN: Oxygen free radicals and the gastrointestinal tract: role in ischemia-reperfusion injury. Hepatogastroenterology41,337–342 (1994).
  Medline CASGoogle Scholar
• 39  Yeh KY, Yeh M, Glass J, Granger DN: Rapid activation of NF-κB and AP-1 and target gene expression in postischemic rat intestine. Gastroenterology118,525–534 (2000).
  Medline CASGoogle Scholar
• 40  Nussler NC, Muller AR, Weidenbach H et al.: IL-10 increases tissue injury after selective intestinal ischemia/reperfusion. Ann. Surg.238,49–58 (2003).
  MedlineGoogle Scholar
• 41  Sonnino R, Ereso G, Arcuni J, Franson R: Human intestinal fatty acid binding protein in peritoneal fluid is a marker of intestinal ischemia. Transplant. Proc.32,1280 (2000).
  Medline CASGoogle Scholar
• 42  Mittak M, Karlik T: Diagnostics of intestinal ischemia. Influence of surgery on plasma levels of I-FABP as the marker of enterocyte injury. Rozhl Chir87,16–20 (2008).
  Medline CASGoogle Scholar
• 43  Polk JD, Rael LT, Craun ML, Mains CW, Davis-Merritt D, Bar-Or D: Clinical utility of the cobalt–albumin binding assay in the diagnosis of intestinal ischemia. J. Trauma64,42–45 (2008).
  Medline CASGoogle Scholar
• 44  Welborn MB, Oldenburg HS, Hess PJ et al.: The relationship between visceral ischemia, proinflammatory cytokines, and organ injury in patients undergoing thoracoabdominal aortic aneurysm repair. Crit. Care Med.28,3191–3197 (2000).
  Medline CASGoogle Scholar
• 45  Foulds S, Galustian C, Mansfield AO, Schachter M: Transcription factor NF-κB expression and postsurgical organ dysfunction. Ann. Surg.233,70–78 (2001).
  Medline CASGoogle Scholar
• 46  Foulds S, Mireskandari M, Kalu P et al.: Visceral ischemia and neutrophil activation in sepsis and organ dysfunction. J. Surg. Res.75,170–176 (1998).
  Medline CASGoogle Scholar
• 47  Altinyollar H, Boyabatli M, Berberoglu U: D-dimer as a marker for early diagnosis of acute mesenteric ischemia. Thromb. Res.117,463–467 (2006).
  Medline CASGoogle Scholar
• 48  Kurt Y, Akin ML, Demirbas S et al.: D-dimer in the early diagnosis of acute mesenteric ischemia secondary to arterial occlusion in rats. Eur. Surg. Res.37,216–219 (2005).
  Medline CASGoogle Scholar
• 49  Schoots IG, Levi M, Roossink EH, Bijlsma PB, van Gulik TM: Local intravascular coagulation and fibrin deposition on intestinal ischemia-reperfusion in rats. Surgery133,411–419 (2003).
  MedlineGoogle Scholar
• 50  Gunerhan Y, Koksal N, Kayahan M, Eryavuz Y, Sekban H: Diagnostic value of plasminogen activity level in acute mesenteric ischemia. World J. Gastroenterol.14,2540–2543 (2008).
  MedlineGoogle Scholar
• 51  Gill SR, Pop M, Deboy RT et al.: Metagenomic analysis of the human distal gut microbiome. Science312,1355–1359 (2006).▪ Important paper, as it was one of the first studies to examine the complete micriobiome from a genomic perspective, and it has informed a great deal of the theories that underpin systems biology.
  Medline CASGoogle Scholar
• 52  Jia W, Li H, Zhao L, Nicholson JK: Gut microbiota: a potential new territory for drug targeting. Nat. Rev. Drug Discov.7,123–129 (2008).
  Medline CASGoogle Scholar
• 53  Hopkins MJ, Macfarlane GT: Changes in predominant bacterial populations in human faeces with age and with Clostridium difficile infection. J. Med. Microbiol.51,448–454 (2002).
  Medline CASGoogle Scholar
• 54  Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R: Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell118,229–241 (2004).
  Medline CASGoogle Scholar
• 55  Eckburg PB, Bik EM, Bernstein CN et al.: Diversity of the human intestinal microbial flora. Science308,1635–1638 (2005).
  MedlineGoogle Scholar
• 56  Reading NC, Sperandio V: Quorum sensing: the many languages of bacteria. FEMS Microbiol. Lett.254,1–11 (2006).
  Medline CASGoogle Scholar
• 57  Sperandio V, Torres AG, Jarvis B, Nataro JP, Kaper JB: Bacteria–host communication: the language of hormones. Proc. Natl Acad. Sci. USA100,8951–8956 (2003).
  Medline CASGoogle Scholar
• 58  Xing HC, Li LJ, Xu KJ et al.: Intestinal microflora in rats with ischemia/reperfusion liver injury. J. Zhejiang Univ. Sci. B6,14–21 (2005).
  MedlineGoogle Scholar
• 59  Opal SM, Gluck T: Endotoxin as a drug target. Crit. Care Med.31,S57–S64 (2003).
  Medline CASGoogle Scholar
• 60  Swank GM, Deitch EA: Role of the gut in multiple organ failure: bacterial translocation and permeability changes. World. J. Surg.20,411–417 (1996).
  Medline CASGoogle Scholar
• 61  Cicalese L, Billiar TR, Rao AS, Bauer AJ: Interaction between ischemia/reperfusion-induced leukocyte emigration and translocating bacterial enterotoxins on enteric muscle function. Transplant. Proc.29,1815 (1997).
  Medline CASGoogle Scholar
• 62  Turnage RH, Guice KS, Oldham KT: Endotoxemia and remote organ injury following intestinal reperfusion. J. Surg. Res.56,571–578 (1994).
  Medline CASGoogle Scholar
• 63  Nezu Y, Tagawa M, Sakaue Y, Hara Y, Tsuchida S, Ogawa R: Kinetics of endotoxin concentration and tumor necrosis factor-α, interleukin-1β, and interleukin-6 activities in the systemic and portal circulation during small intestinal ischemia and reperfusion in dogs. Am. J. Vet. Res.63,1680–1686 (2002).
  Medline CASGoogle Scholar
• 64  Souza DG, Vieira AT, Soares AC et al.: The essential role of the intestinal microbiota in facilitating acute inflammatory responses. J. Immunol.173,4137–4146 (2004).
  Medline CASGoogle Scholar
• 65  Cruz N, Lu Q, Alvarez X, Deitch EA: Bacterial translocation is bacterial species dependent: results using the human Caco-2 intestinal cell line. J. Trauma36,612–616 (1994).
  Medline CASGoogle Scholar
• 66  O’Boyle CJ, MacFie J, Mitchell CJ, Johnstone D, Sagar PM, Sedman PC: Microbiology of bacterial translocation in humans. Gut42,29–35 (1998).
  MedlineGoogle Scholar
• 67  Clark E, Hoare C, Tanianis-Hughes J, Carlson GL, Warhurst G: Interferon γ induces translocation of commensal Escherichia coli across gut epithelial cells via a lipid raft-mediated process. Gastroenterology128,1258–1267 (2005).
  Medline CASGoogle Scholar
• 68  Nazli A, Yang PC, Jury J et al.: Epithelia under metabolic stress perceive commensal bacteria as a threat. Am. J. Pathol.164,947–957 (2004).
  MedlineGoogle Scholar
• 69  Spahn TW, Kucharzik T: Modulating the intestinal immune system: the role of lymphotoxin and GALT organs. Gut53,456–465 (2004).
  Medline CASGoogle Scholar
• 70  Garside P, Millington O, Smith KM: The anatomy of mucosal immune responses. Ann. NY Acad. Sci.1029,9–15 (2004).
  Medline CASGoogle Scholar
• 71  Song F, Whitacre CC: The role of the gut lymphoid tissue in induction of oral tolerance. Curr. Opin Investig. Drugs2,1382–1386 (2001).
  Medline CASGoogle Scholar
• 72  Ayten R, Dogru O, Camci C, Aygen E, Cetinkaya Z, Akbulut H: Predictive value of procalcitonin for the diagnosis of bowel strangulation. World J. Surg.29,187–189 (2005).
  MedlineGoogle Scholar
• 73  Papaziogas B, Anthimidis G, Koutelidakis I, Atmatzidis S, Atmatzidis K: Predictive value of procalcitonin for the diagnosis of bowel strangulation. World J. Surg.32,1566–1567 (2008).
  Medline CASGoogle Scholar
• 74  Gunel E, Caglayan O, Caglayan F: Serum D-lactate levels as a predictor of intestinal ischemia–reperfusion injury. Pediatr. Surg. Int.14,59–61 (1998).
  Medline CASGoogle Scholar
• 75  Murray MJ, Gonze MD, Nowak LR, Cobb CF: Serum D(-)-lactate levels as an aid to diagnosing acute intestinal ischemia. Am. J. Surg.167,575–578 (1994).
  Medline CASGoogle Scholar
• 76  Collange O, Tamion F, Chanel S et al.: D-lactate is not a reliable marker of gut ischemia–reperfusion in a rat model of supraceliac aortic clamping. Crit. Care Med.34,1415–1419 (2006).
  Medline CASGoogle Scholar
• 77  Scanlan PD, Shanahan F, Clune Y et al.: Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ. Microbiol.10,789–798 (2008).
  Medline CASGoogle Scholar
• 78  Dumas ME, Barton RH, Toye A et al.: Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc. Natl Acad. Sci. USA103,12511–12516 (2006).
  Medline CASGoogle Scholar
• 79  Nicholson JK, Holmes E, Wilson ID: Gut microorganisms, mammalian metabolism and personalized health care. Nat. Rev. Microbiol.3,431–438 (2005).
  Medline CASGoogle Scholar
• 80  Wang Y, Tang H, Nicholson JK, Hylands PJ, Sampson J, Holmes E: A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion. J. Agric. Food Chem.53,191–196 (2005).
  Medline CASGoogle Scholar
• 81  Holmes E, Nicholson J: Variation in gut microbiota strongly influences individual rodent phenotypes. Toxicol. Sci.87,1–2 (2005).
  Medline CASGoogle Scholar
• 82  Martin FP, Wang Y, Sprenger N et al.: Probiotic modulation of symbiotic gut microbial–host metabolic interactions in a humanized microbiome mouse model. Mol. Syst. Biol.4,157 (2008).
  MedlineGoogle Scholar
• 83  Clayton TA, Lindon JC, Cloarec O et al.: Pharmaco–metabonomic phenotyping and personalized drug treatment. Nature440,1073–1077 (2006).▪▪ Describes the paradigm of ‘pharmacometabonomics’ and the wider impact of the gut microbiome on the capacity of mammals to safely metabolize drugs.
  Medline CASGoogle Scholar
• 84  Saxena V, Gupta A, Nagana Gowda GA, Saxena R, Yachha SK, Khetrapal CL: ¹H NMR spectroscopy for the prediction of therapeutic outcome in patients with fulminant hepatic failure. NMR Biomed.19,521–526 (2006).
  Medline CASGoogle Scholar
• 85  Mayr M, Yusuf S, Weir G et al.: Combined metabolomic and proteomic analysis of human atrial fibrillation. J. Am. Coll. Cardiol.51,585–594 (2008).
  Medline CASGoogle Scholar
• 86  Lindon JC, Holmes E, Bollard ME, Stanley EG, Nicholson JK: Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis. Biomarkers9,1–31 (2004).
  Medline CASGoogle Scholar
• 87  Constantinou MA, Tsantili-Kakoulidou A, Andreadou I, Iliodromitis EK, Kremastinos DT, Mikros E: Application of NMR-based metabonomics in the investigation of myocardial ischemia–reperfusion, ischemic preconditioning and antioxidant intervention in rabbits. Eur. J. Pharm. Sci.30,303–314 (2007).
  Medline CASGoogle Scholar
• 88  Viant MR, Lyeth BG, Miller MG, Berman RF: An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model. NMR Biomed.18,507–516 (2005).
  Medline CASGoogle Scholar
• 89  So PW, Busza AL, Fuller BJ: Metabolic effects of citrate in liver during cold hypoxia studied by ¹H NMR spectroscopy. Cryobiology36,225–235 (1998).
  Medline CASGoogle Scholar
• 90  Serkova N, Fuller TF, Klawitter J, Freise CE, Niemann CU: H-NMR-based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants. Kidney Int.67,1142–1151 (2005).
  Medline CASGoogle Scholar
• 91  Kimmich GA, Randles J, Brand JS: Assay of picomole amounts of ATP, ADP, and AMP using the luciferase enzyme system. Anal. Biochem.69,187–206 (1975).
  Medline CASGoogle Scholar
• 92  Kass DA, Banville DL, Gooding CA, James TL: ³¹P magnetic resonance spectroscopy of mesenteric ischemia. Magn. Reson. Med.4,83–87 (1987).
  Medline CASGoogle Scholar
• 93  Taylor BM, Jamieson WG, Durand D: Preinfarction diagnosis of acute mesenteric ischemia by simple measurement of inorganic phosphate in body fluids. Can. J. Surg.22,40–45 (1979).
  Medline CASGoogle Scholar
• 94  Jamieson WG, Marchuk S, Rowsom J, Durand D: The early diagnosis of massive acute intestinal ischaemia. Br. J. Surg.69,S52–S53 (1982).
  MedlineGoogle Scholar
• 95  Sato A, Kataoka M, Kuwabara Y, Kimura M, Seo Y, Masaoka A: Ischemic injury of the small intestine studied by ³¹P-MRS. J. Surg. Res.61,373–378 (1996).
  Medline CASGoogle Scholar
• 96  Sato A, Kuwabara Y, Sugiura M, Seo Y, Fujii Y: Intestinal energy metabolism during ischemia and reperfusion. J. Surg. Res.82,261–267 (1999).
  Medline CASGoogle Scholar
• 97  Wevers RA, Engelke UF, Moolenaar SH et al.: ¹H-NMR spectroscopy of body fluids: inborn errors of purine and pyrimidine metabolism. Clin. Chem.45,539–548 (1999).
  Medline CASGoogle Scholar
• 98  Blum H, Summers JJ, Schnall MD et al.: Acute intestinal ischemia studies by phosphorus nuclear magnetic resonance spectroscopy. Ann. Surg.204,83–88 (1986).
  Medline CASGoogle Scholar
• 99  Blum H, Summers JJ, Schnall MD, Leigh JS, Chance B, Buzby GP: Acute occlusive intestinal ischemia studied by phosphorus-31 nuclear magnetic resonance. Curr. Surg.43,482–485 (1986).
  Medline CASGoogle Scholar
• 100  Kuwabara Y, Kato T, Sato A, Fujii Y: Prolonged effect of leukocytosis on reperfusion injury of rat intestine: real-time ATP change studied using (³¹)P MRS. J. Surg. Res.89,38–42 (2000).
  Medline CASGoogle Scholar
• 101  Canada AT, Coleman LR, Fabian MA Jr, Bollinger RR: Adenine nucleotides of ischemic intestine do not reflect injury. J. Surg. Res.55,416–421 (1993).
  Medline CASGoogle Scholar
• 102  Temes RT, Kauten RJ, Schwartz MZ: Nuclear magnetic resonance as a noninvasive method of diagnosing intestinal ischemia: technique and preliminary results. J. Pediatr. Surg.26,775–779 (1991).
  Medline CASGoogle Scholar
• 103  Kimura M, Kataoka M, Kuwabara Y, Sato A, Sugiura M, Fujii Y: Real-time energy metabolism of intestine during arterial versus venous occlusion in the rat. J. Gastroenterol.38,849–853 (2003).
  MedlineGoogle Scholar
• 104  Vejchapipat P, Proctor E, Ramsay A et al.: Intestinal energy metabolism after ischemia–reperfusion: effects of moderate hypothermia and perfluorocarbons. J. Pediatr. Surg.37,786–790 (2002).
  MedlineGoogle Scholar
• 105  Sugiura M, Kuwabara Y, Mitani M et al.: Effect of whole body hyperthermia on ischemia and reperfusion injury of rat intestine: real-time ATP change studied using (³¹)P-MRS. Eur. Surg. Res.34,306–312 (2002).
  Medline CASGoogle Scholar
• 106  Hiratsuka M, Yano M, Mora BN, Nagahiro I, Cooper JD, Patterson GA: Heat shock pretreatment protects pulmonary isografts from subsequent ischemia–reperfusion injury. J. Heart Lung Transplant17,1238–1246 (1998).
  Medline CASGoogle Scholar
• 107  Vejchapipat P, Williams SR, Spitz L, Pierro A: Intestinal metabolism after ischemia-reperfusion. J. Pediatr. Surg.35,759–764 (2000).
  Medline CASGoogle Scholar
• 108  Mitchell SJ, Churchill TA, Winslet MC, Fuller BJ: Effects of different cold preservation solutions on restoration of hepatic energy metabolism during cold reperfusion. Cryobiology33,413–422 (1996).
  Medline CASGoogle Scholar
• 109  Lindon JC, Nicholson JK, Holmes E et al.: Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project. Toxicol. Appl. Pharmacol.187,137–146 (2003).
  Medline CASGoogle Scholar
• 110  Wang Y, Cloarec O, Tang H et al.: Magic Angle Spinning NMR and (¹)H–(³¹)P heteronuclear statistical total correlation spectroscopy of intact human gut biopsies. Anal. Chem.80,1058–1066 (2008).
  Medline CASGoogle Scholar
• 111  Makinen VP, Soininen P, Forsblom C et al.: ¹H NMR metabonomics approach to the disease continuum of diabetic complications and premature death. Mol. Syst. Biol.4,167 (2008).
  MedlineGoogle Scholar
• 112  Bollard ME, Stanley EG, Lindon JC, Nicholson JK, Holmes E: NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition. NMR Biomed.18,143–162 (2005).
  Medline CASGoogle Scholar
• 113  Stanley EG, Bailey NJ, Bollard ME et al.: Sexual dimorphism in urinary metabolite profiles of Han Wistar rats revealed by nuclear-magnetic-resonance-based metabonomics. Anal. Biochem.343,195–202 (2005).
  Medline CASGoogle Scholar
• 114  Deitch EA, Ananthakrishnan P, Cohen DB, Xu da Z, Feketeova E, Hauser CJ: Neutrophil activation is modulated by sex hormones after trauma-hemorrhagic shock and burn injuries. Am. J. Physiol. Heart Circ. Physiol.291,H1456–H1465 (2006).
  Medline CASGoogle Scholar
• 115  Lindon JC, Nicholson JK, Holmes E et al.: Summary recommendations for standardization and reporting of metabolic analyzes. Nat. Biotechnol.23,833–838 (2005).
  Medline CASGoogle Scholar
• 116  Samani NJ, Burton P, Mangino M et al.: A genomewide linkage study of 1,933 families affected by premature coronary artery disease: The British Heart Foundation (BHF) Family Heart Study. Am. J. Hum. Genet.77,1011–1020 (2005).
  MedlineGoogle Scholar
• 117  Feezor RJ, Baker HV, Xiao W et al.: Genomic and proteomic determinants of outcome in patients undergoing thoracoabdominal aortic aneurysm repair. J. Immunol.172,7103–7109 (2004).
  Medline CASGoogle Scholar
• 118  Martin SL, Epperson LE, Rose JC, Kurtz CC, Ane C, Carey HV: Proteomic analysis of the winter-protected phenotype of hibernating ground squirrel intestine. Am. J. Physiol. Regul. Integr. Comp. Physiol.295,R316–R328 (2008).
  Medline CASGoogle Scholar
• 119  Lee C, Morton CC: Structural genomic variation and personalized medicine. N. Engl. J. Med.358,740–741 (2008).
  Medline CASGoogle Scholar
• 120  Martin FP, Dumas ME, Wang Y et al.: A top-down systems biology view of microbiome–mammalian metabolic interactions in a mouse model. Mol. Syst. Biol.3,112 (2007).
  MedlineGoogle Scholar
• 121  Knickerbocker T, Chen JR, Thadhani R, MacBeath G: An integrated approach to prognosis using protein microarrays and nonparametric methods. Mol. Syst. Biol.3,123 (2007).
  MedlineGoogle Scholar
• 122  Kurimoto Y, Kawaharada N, Ito T, Morikawa M, Higami T, Asai Y: An experimental evaluation of the lactate concentration following mesenteric ischemia. Surg. Today38,926–930 (2008).
  Medline CASGoogle Scholar
• 123  Caglayan F, Caglayan O, Gunel E, Elcuman Y, Cakmak M: Intestinal ischemia–reperfusion and plasma enzyme levels. Pediatr. Surg. Int.18,255–257 (2002).
  MedlineGoogle Scholar
• 124  Koike K, Yamamoto Y, Hori Y, Ono T: Group IIA phospholipase A2 mediates lung injury in intestinal ischemia–reperfusion. Ann. Surg.232,90–97 (2000).
  Medline CASGoogle Scholar
• 125  de Arruda MJ, Poggetti RS, Fontes B, Younes RN, Souza AL, Birolini D Jr: Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-α in rats. Clinics61,21–28 (2006).
  MedlineGoogle Scholar
• 126  Yamamoto S, Tanabe M, Wakabayashi G, Shimazu M, Matsumoto K, Kitajima M: The role of tumor necrosis factor-α and interleukin-1β in ischemia-reperfusion injury of the rat small intestine. J. Surg. Res.99,134–141 (2001).
  Medline CASGoogle Scholar
• 127  Wang JY, Cheng KI, Yu FJ, Tsai HL, Huang TJ, Hsieh JS: Analysis of the correlation of plasma NO and ET-1 levels in rats with acute mesenteric ischemia. J. Invest. Surg.19,155–161 (2006).
  MedlineGoogle Scholar
• 128  Juvonen PO, Paajanen HE, Heino AA et al.: Lipid peroxidation products and antioxidant capacity in portal venous and systemic arterial plasma during gradual intestinal ischemia and reperfusion in pigs. Eur. Surg. Res.30,95–101 (1998).
  Medline CASGoogle Scholar
• 129  Vejchapipat P, Williams SR, Proctor E, Lauro V, Spitz L, Pierro A: Moderate hypothermia ameliorates liver energy failure after intestinal ischaemia–reperfusion in anaesthetized rats. J. Pediatr. Surg.36,269–275 (2001).
  Medline CASGoogle Scholar