nach oben

World Journal of Surgery

Erschienen in:

01.02.2008

The Potential Role for Xanthine Oxidase Inhibition in Major Intra-abdominal Surgery

verfasst von: Anubhav Mittal, Anthony R. J. Phillips, Benjamin Loveday, John A. Windsor

Erschienen in: World Journal of Surgery | Ausgabe 2/2008

Einloggen, um Zugang zu erhalten

Abstract

Background

Xanthine oxidase (XO) is a cytosolic metalloflavoprotein that has been implicated in the pathogenesis of a wide spectrum of diseases, and is thought to be the most important source of oxygen-free radicals and cell damage during re-oxygenation of hypoxic tissues. Clinical studies have already shown that XO inhibition is safe and effective for the treatment of gout, tumour-lysis syndrome, and to reduce complications such as post-operative arrhythmias, myocardial infarction and mortality in cardiovascular surgery. Here, we review the evidence from two decades of animal studies that have investigated the effects of XO inhibition during intra-abdominal surgery.

Materials and methods

A search of the Ovid MEDLINE database from 1950 through January 2007 was carried out using the following search terms: xanthine oxidase, allopurinol, ischemia, reperfusion, intestine, bowel, and general surgery.

Results

The inhibition of XO has been shown to reduce oxidative stress, neutrophil priming, damage to intestinal mucosa due to ischemia reperfusion injuries, intestinal anastomotic dehiscence, bacterial translocation, adhesion formation, distant organ injury and mortality.

Conclusions

Despite this evidence which very strongly suggests a likely clinically beneficial role for XO inhibition in the elective and acute operative setting, it is surprising that such an approach has not been investigated in general surgery. There is now sufficient evidence to justify dedicated studies to determine the clinical benefits, dosing and duration of XO inhibition before and after gastrointestinal surgery.

Massey V, Harris CM (1997) Milk xanthine dehydrogenase: the first one hundred years. Biochem Soc Trans 25:750–755PubMed

Blauch M, Koch F, Hanke M (1939) A study of xanthine oxidase of rat blood. J Biol Chem 130:471–486

Borges F, Fernandes E, Roleira F (2002) Progress towards the discovery of xanthine oxidase inhibitors. Curr Med Chem 9:195–217PubMed

Parks DA, Granger DN (1986) Xanthine oxidase: biochemistry, distribution and physiology. Acta Physiol Scand 548(Suppl):87–99

Pacher P, Nivorozhkin A, Szabo C (2006) Therapeutic effects of xanthine oxidase inhibition: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58:87–114PubMedCrossRef

Meneshian A, Bulkley GB (2002) The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction. Microcirculation 9:161–175PubMedCrossRef

Parks D, Skinner K, Skinner H et al. (1998) Multiple organ dysfunction syndrome: role of xanthine oxidase and nitric oxide. Pathophysiology 5:49–66CrossRef

Folch E, Gelpi E, Rosello-Catafau J et al. (1998) Free radicals generated by xanthine oxidase mediate pancreatitis-associated organ failure. Dig Dis Sci 43:2405–2410PubMedCrossRef

Granell S, Bulbena O, Genesca M et al. (2004) Mobilization of xanthine oxidase from the gastrointestinal tract in acute pancreatitis. BMC Gastroenterology 4:1PubMedCrossRef

10.

Ichida K, Amaya Y, Noda K et al. (1993) Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene. Gene 133:279–284PubMedCrossRef

11.

Glantzounis GK, Tsimoyiannis EC, Kappas AM et al. (2005) Uric acid and oxidative stress. Curr Pharm Des 11:4145–4151PubMedCrossRef

12.

Engerson TD, McKelvey TG, Rhyne DB et al. (1987) Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J Clin Invest 79:1564–1570PubMed

13.

Mallick I, Yang W, Winslet M et al. (2004) Ischemia–reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 49:1359–1377PubMedCrossRef

14.

Chung H, Baek B, Song S et al. (1997) Xanthine dehydrogenase/xanthine oxidase and oxidative stress. Age 20:127–140CrossRef

15.

Houston M, Estevez A, Chumley P et al. (1999) Binding of xanthine oxidase to vascular endothelium. Kinetic characterization and oxidative impairment of nitric oxide-dependent signaling. J Biol Chem 274:4985–4994PubMedCrossRef

16.

Martin H, Hancock J, Salisbury V et al. (2004) Role of xanthine oxidoreductase as an antimicrobial agent. Infection and immunity 72:4933–4939PubMedCrossRef

17.

Tan S, Gelman S, Wheat J et al. (1995) Circulating xanthine oxidase in human ischemia reperfusion. South Med J 88:479–482PubMed

18.

Granell S, Gironella M, Bulbena O et al. (2003) Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis. Crit Care Med 31:525–530PubMedCrossRef

19.

Schimpl G, Pabst MA, Feierl G et al. (1999) A tungsten supplemented diet attenuates bacterial translocation in chronic portal hypertensive and cholestatic rats: role of xanthine dehydrogenase and xanthine oxidase. Gut 45:904–910PubMed

20.

Thomas S, Pulimood A, Balasubramanian KA (2003) Heat preconditioning prevents oxidative stress-induced damage in the intestine and lung following surgical manipulation. Br J Surg 90:473–481PubMedCrossRef

21.

Thomas S, Ramachandran A, Ramamoorthy P et al. (2001) Effect of surgical manipulation of the rat intestine on enterocyte populations. Surgery 130:479–488CrossRef

22.

Anup R, Susama P, Balasubamanian KA (2001) Intestinal mitochondrial dysfunction induced by surgical stress. J Surg Res 99:120–128CrossRef

23.

Kalff J, Schraut W, Simmons R et al. (1998) Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg 228:652–663PubMedCrossRef

24.

Thomas S, Ramamoorthy P, Balasubamanian KA (2005) Surgical manipulation of the intestine and distant organ damage—protection by oral glutamine supplementation. Surgery 137:48–55PubMedCrossRef

25.

Anup R, Susama P, Balasubamanian KA (2000) Role of xanthine oxidase in small bowel mucosal dysfunction after surgical stress. Br J Surg 87:1094–1101PubMedCrossRef

26.

Ramachandran A, Susama P, Balasubamanian KA (2001) Intestinal mitochondrial dysfunction induced by surgical stress. J Surg Res 99:120–128PubMedCrossRef

27.

Galley H, Davies M, Webster N (1996) Xanthine oxidase activity and free radical generation in patients with sepsis syndrome. Crit Care Med 24:1649–1653PubMedCrossRef

28.

Reilly PM, Wilkins KB, Fuh KC et al. (2001) The mesenteric hemodynamic response to circulatory shock: an overview. Shock 15:329–343PubMed

29.

Ceppa EP, Fuh KC, Bulkley GB (2003) Mesenteric hemodynamic response to circulatory shock. Curr Opin Crit Care 9:127–132PubMedCrossRef

30.

Oldenburg W, Lau L, Rodenberg T et al. (2004) Acute mesenteric ischemia. Arch Intern Med 164:1054–1062PubMedCrossRef

31.

Lundberg J, Lundberg D, Norgren L et al. (1990) Intestinal hemodynamics during laparotomy: effects of thoracic epidural anesthesia and dopamine in humans. Anesth Analg 72:9–15

32.

Holland J, Carey M, Hughes N et al. (2005) Intraoperative splanchnic hypoperfusion, increased intestinal permeability, down-regulation of monocyte class II major histocompatibility complex expression, exaggerated acute phase response, and sepsis. Am J Surg 190:393–400PubMedCrossRef

33.

Stollman N, Metz D (2005) Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care 20:35–45PubMedCrossRef

34.

Yilmaz S, Koken T, Tokyol C et al. (2003) Can preconditioning reduce laparoscopy-induced tissue injury. Surg Endosc 17:819–824PubMedCrossRef

35.

Emir H, Akman M, Belce A et al. (2001) Is intestinal ischaemia a risk of laparoscopy? An experimental study in rabbits. Eur J Paediatr Surg 11:158–162CrossRef

36.

Hasson H, Galanopoulos C, Langerman A (2004) Ischemic necrosis of small bowel following laparoscopic surgery. JSLS 8:159–163PubMed

37.

Xian-Ping L, Ya-Xiong S, Cheng-Ren S et al. (1995) Changes in body fluid markers in intestinal ischemia. J Pediatr Surg 30:1412–1415CrossRef

38.

Prichard M, Norm G, Ducharme P et al. (1991) Xanthine oxidase formation during experimental ischemia of the equine small intestine. Can J Vet Res 55:310–314PubMed

39.

Cizova H, Papezikova I, Kubala L et al. (2006) Increased antioxidant capacity of serum did not prevent lipid peroxidation in the intermittent ischemia–reperfusion of rat small intestine. Dig Dis Sci 51:657–661PubMedCrossRef

40.

Wilkins EG, Rees RS, Smith D (1993) Identification of xanthine oxidase activity following reperfusion in human tissue. Ann Plast Surg 31:60–65PubMed

41.

Lammers K, Innocenti G, Venturi A (2003) The effect of transient intestinal ischemia on inflammatory parameters. Int J Colorectal Dis 18:78–85PubMedCrossRef

42.

Flynn W, Pilati D, Hoover E (1997) Xanthine oxidase inhibition after resuscitated hemorrhagic shock restores mesenteric blood flow without vasodilation. Shock 8:300–304PubMed

43.

Flynn W, Pilati D, Hoover E (1997) Xanthine oxidase inhibition prevents mesenteric blood flow deficits after resuscitated shock by preserving endothelial function. J Surg Res 68:175–180PubMedCrossRef

44.

Flynn W, Pilati D, Hoover E (1999) Effect of allopurinol on venous endothelial dysfunction after resuscitated hemorrhagic shock. Int J Surg Invest 1:11–18

45.

Flynn W, Hoover E (1994) Allopurinol plus standard resuscitation preserves hepatic blood flow and function following hemorrhagic shock. J Trauma 37:956–961PubMed

46.

Pitt RM, McKelvey TG, Saenger JS et al. (1991) A tungsten-supplemented diet delivered by transplacental and breast-feeding routes lowers intestinal xanthine oxidase activity and affords cytoprotection in ischemia–reperfusion injury to the small intestine. J Pediatr Surg 26:930–935PubMedCrossRef

47.

Megison SM, Horton JW, Chao H et al. (1990) Prolonged survival and decreased mucosal injury after low-dose enteral allopurinol prophylaxis in mesenteric ischemia. J Pediatr Surg 25:917–921PubMedCrossRef

48.

Krasna I, Lee R (1993) Allopurinol protects the bowel from necrosis caused by indomethacin and temporary intestinal ischemia in mice. J Pediatr Surg 28:1175–1177PubMedCrossRef

49.

Van Hoorn D, Nijveldt R, Boelens P et al. (2006) Effects of preoperative flavonoid supplementation on different organ function in rats. J Parental Enteral Nutr 30:302–308CrossRef

50.

Hakguder G, Akgur FM, Ates O et al. (2002) Short-term intestinal ischemia–reperfusion alters intestinal motility that can be preserved by xanthine oxidase inhibition. Dig Dis Sci 47:1279–1283PubMedCrossRef

51.

Megison SM, Horton JW, Chao H et al. (1990) High dose versus low dose enteral allopurinol for prophylaxis in mesenteric ischemia. Circ Shock 30:323–329PubMed

52.

Terzi C, Kuzu A, Aslar AK et al. (2001) Prevention of deleterious effects of reperfusion injury using one-week high-dose allopurinol. Dig Dis Sci 46:430–437PubMedCrossRef

53.

Grisham MB, Hernandez LA, Granger DN (1986) Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol 251(4 Pt 1):G567–G574PubMed

54.

Koike K, Moore FA, Moore EE et al. (1993) Gut ischemia mediates lung injury by a xanthine oxidase-dependent neutrophil mechanism. J Surg Res 54:469–473PubMedCrossRef

55.

Nalini S, Mathan MM, Balasubramanian KA (1993) Oxygen free radical induced damage during intestinal ischemia/reperfusion in normal and xanthine oxidase deficient rats. Mol Cell Biochem 124:59–66PubMedCrossRef

56.

Vaughan WG, Horton JW, Walker PB (1992) Allopurinol prevents intestinal permeability changes after ischemia–reperfusion injury. J Pediatr Surg 27:968–972; discussion 972–963PubMedCrossRef

57.

Ferrer JV, Ariceta J, Guerrero D et al. (1998) Allopurinol and n-acetylcysteine avoid 60% of intestinal necrosis in an ischemia–reperfusion experimental model. Transplant Proc 30:2672PubMedCrossRef

58.

Sola A, Hotter G, Parts N et al. (2000) Modification of oxidative stress in response to intestinal preconditioning. Transplantation 69:767–772PubMedCrossRef

59.

Sola A, Alfaro V, Hotter G (2004) Intestinal ischemic preconditioning: less xanthine accumulation relates with less apoptosis. Apoptosis 9:353–361PubMedCrossRef

60.

Sandrasegaran K, Maglinte D, Lappas J (2004) Small-bowel complications of major gastrointestinal tract surgery. AJR Am J Roentgenol 185:671–681

61.

Slim K, Vicaut E, Panis Y et al. (2004) Meta-analysis of randomized clinical trials of colorectal surgery with or without mechanical bowel preparation. Br J Surg 91:1125–1130PubMedCrossRef

62.

Calicis B, Parc Y, Caplin S et al. (2002) Treatment of postoperative peritonitis of small-bowel origin with continuous enteral nutrition and succus entericus reinfusion. Arch Surg 137:296–300PubMedCrossRef

63.

Baker J, Deitch EA, Li M et al. (1988) Hemorrhagic shock induces bacterial translocation from the gut. J Trauma 28:896–906PubMedCrossRef

64.

Rush B, Fedan J, Flanagan J et al. (1989) Does the bacteremia observed in hemorrhagic shock have clinical significance? Ann Surg 210:342–345PubMedCrossRef

65.

Celik A, Aydemir S, Alkanat M et al. (2005) Hemorrhagic shock and bacterial translocation. J Appl Res 5:196–205

66.

Sedman P, MacFie J, Sagar P et al. (1994) The prevalence of gut translocation in humans. Gastroenterology 107:643–649PubMed

67.

Deitch EA, Bridges W, Baker J et al. (1998) Hemorrhagic shock-induced bacterial translocation is reduced by xanthine oxidase inhibition or inactivation. Surgery 104:191–198

68.

Senthilkumar MP, Dreyer JS (2006) Peritoneal adhesions: pathogenesis, assessment and effects. Trop Gastroenterol 27:11–18PubMed

69.

Ellis H (1962) The aetiology of postoperative abdominal adhesions. Br J Surg 50:10–16PubMedCrossRef

70.

Rijhwani A, Sen S, Gunasekaran S et al. (1995) Allopurinol reduces the severity of peritoneal adhesions in mice. J Pediatr Surg 30:533–537PubMedCrossRef

71.

Hall JC, Tarala RA, Hall JL et al. (1991) A multivariate analysis of the risk of pulmonary complications after laparotomy. Chest 99:923–927PubMedCrossRef

72.

Lawrence V, Hilsenbeck S, Mulrow C et al. (1995) Incidence and hospital stay for cardiac and pulmonary complications after abdominal surgery. J Gen Intern Med 10:671–678PubMedCrossRef

73.

Terada LS, Dormish JJ, Shanley PF et al. (1992) Circulating xanthine oxidase mediates lung neutrophil sequestration after intestinal ischemia–reperfusion. Am J Physiol 263(3 Pt 1):L394–L401PubMed

74.

Thomas S, Karnik S, Balasubamanian KA (2002) Surgical manipulation of the small intestine and its effect on the lung. J Surg Res 106:145–156PubMedCrossRef

75.

Nakamura M, Motoyama S, Saito S et al. (2004) Hydrogen peroxide derived from the intestine through mesenteric lymph induces lung edema after surgical stress. Shock 21:160–164PubMedCrossRef

76.

Nielsen VG, Tan S, Baird MS et al. (1997) Xanthine oxidase mediates myocardial injury after hepatoenteric ischemia–reperfusion. Crit Care Med 25:1044–1050PubMedCrossRef

77.

Lai I, Ma M, Chen C et al. (2003) The effect of an intestinal ischemia–reperfusion injury on renal nerve activity among rats. Shock 19:480–485PubMedCrossRef

78.

Ramachandran A, Balasubamanian KA (2000) Protease activation during surgical stress in the rat small intestine. J Surg Res 92:283–290PubMedCrossRef

79.

Smalley R, Guaspari A, Hasse-Statz S et al. (2000) Allopurinol: intravenous use for prevention and treatment of hyperuricemia. J Clin Oncol 18:1758–1763PubMed

80.

Nijveldt R, van Nood E, van Hoorn D et al. (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74:418–425PubMed

81.

Cohen DB, Magnotti LJ, Lu Q et al. (2004) Pancreatic duct ligation reduces lung injury following trauma and hemorrhagic shock. Ann Surg 240:885–891PubMedCrossRef

82.

Deitch EA, Shi HP, Lu Q et al. (2003) Serine proteases are involved in the pathogenesis of trauma-hemorrhagic shock-induced gut and lung injury. Shock 19:452–456PubMedCrossRef

83.

Ishimaru K, Mitsuoka H, Unno N et al. (2004) Pancreatic proteases and inflammatory mediators in peritoneal fluid during splanchnic arterial occlusion and reperfusion. Shock 22:467–471PubMedCrossRef

84.

Fitzal F, DeLano FA, Young C et al. (2004) Improvement in early symptoms of shock by delayed intestinal protease inhibition. Arch Surg 139:1008–1016PubMedCrossRef

85.

Fitzal F, DeLano FA, Young C et al. (2002) Pancreatic protease inhibition during shock attenuates cell activation and peripheral inflammation. Journal of Vascular Research 39:320–329PubMedCrossRef

86.

Mitsuoka H, Kistler EB, Schmid-Schonbein GW (2002) Protease inhibition in the intestinal lumen: attenuation of systemic inflammation and early indicators of multiple organ failure in shock. Shock 17:205–209PubMedCrossRef

Titel: The Potential Role for Xanthine Oxidase Inhibition in Major Intra-abdominal Surgery
verfasst von: Anubhav Mittal
Anthony R. J. Phillips
Benjamin Loveday
John A. Windsor
Publikationsdatum: 01.02.2008
Verlag: Springer-Verlag
Erschienen in: World Journal of Surgery / Ausgabe 2/2008
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-007-9336-4

Neu im Fachgebiet Chirurgie

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren.

Wie sieht der OP der Zukunft aus?

04.05.2024 DCK 2024 Kongressbericht

Der OP in der Zukunft wird mit weniger Personal auskommen – nicht, weil die Technik das medizinische Fachpersonal verdrängt, sondern weil der Personalmangel es nötig macht.

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Recycling im OP – möglich, aber teuer

02.05.2024 DCK 2024 Kongressbericht

Auch wenn sich Krankenhäuser nachhaltig und grün geben – sie tragen aktuell erheblich zu den CO₂-Emissionen bei und produzieren jede Menge Müll. Ein Pilotprojekt aus Bonn zeigt, dass viele Op.-Abfälle wiederverwertet werden können.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare

CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare

CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske

Dr. med. Benjamin Meyknecht

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare

CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric

Springer Medizin

Abstract

Background

Materials and methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2008

CRC Surgery Trends in Kenya, 1993–2005

Artificial Neural Networks: Useful Aid in Diagnosing Acute Appendicitis

Reply

New Technologies for the Surgical Curriculum

Long-term Results after Dissection of Positive Thoracic Lymph Nodes in Patients with Esophageal Squamous Cell Carcinoma

Proton Pump Inhibitors Relieve and Prevent Symptoms Related to Gastric Acidity after Esophagectomy

Update Chirurgie