International Journal of Colorectal Disease

, Volume 24, Issue 8, pp 975–981 | Cite as

Ischemic preconditioning improves stability of intestinal anastomoses in rats

  • Goran Marjanovic
  • Eva Jüttner
  • Axel zur Hausen
  • Ulrich Theodor Hopt
  • Robert Obermaier
Original Article

Abstract

Background

The aim of our study was to establish whether ischemic preconditioning (IPC) directly before performing a small bowel anastomosis has an effect on anastomotic stability and healing.

Material and methods

Forty male Wistar rats were randomized to five groups: control (CO, n = 8) with preparation of the superior mesenteric artery (SMA) but without IPC. IPC groups had different intervals of ischemia (occlusion of the SMA) and reperfusion: 10 min ischemia and 20 min reperfusion (IPC10/20, n = 7), 10 min ischemia and 30 min reperfusion (IPC10/30, n = 8), 15 min ischemia and 20 min reperfusion (IPC15/20, n = 8), and 15 min ischemia and 30 min reperfusion (IPC15/30, n = 9). On the fourth postoperative day, the animals were relaparotomized: bursting pressure, hydroxyproline concentration, and histological ischemia mucosal injury scale of the anastomosis were assessed.

Results

Four days after operation, the mean bursting pressure was 73 ± 6 mmHg in the control group, whereas it was significantly higher in IPC10/20 (113 ± 11 mmHg; p = 0.018), IPC10/30 (110 ± 13 mmHg; p = 0.001), and IPC15/30 (124 ± 9 mmHg; p = 0.003). IPC15/20 did not show a significant difference (63 ± 2 mmHg; p = 0.4). We did not find a significant effect regarding hydroxyproline concentration, but IPC diminished mucosal injury.

Conclusions

IPC directly before performing a small bowel anastomosis has a time-dependent beneficial effect on anastomotic stability, thus indicating a new clinical approach to improve the healing process of intestinal anastomosis.

Keywords

Ischemic preconditioning Anastomotic healing Intestinal anastomoses Stability of intestinal anastomoses Ischemia reperfusion 

References

  1. 1.
    Fielding LP, Stewart-Brown S, Blesovsky L, Kearney G (1980) Anastomotic integrity after operations for large-bowel cancer: a multicentre study. Br Med J 281:411–414PubMedCrossRefGoogle Scholar
  2. 2.
    Thompson SK, Chang EY, Jobe BA (2006) Clinical review: healing in gastrointestinal anastomoses, part I. Microsurgery 26:131–136PubMedCrossRefGoogle Scholar
  3. 3.
    Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136PubMedGoogle Scholar
  4. 4.
    Koti RS, Yang W, Dashwood MR, Davidson BR, Seifalian AM (2002) Effect of ischemic preconditioning on hepatic microcirculation and function in a rat model of ischemia reperfusion injury. Liver Transpl 8:1182–1191PubMedCrossRefGoogle Scholar
  5. 5.
    Pang CY, Neligan P, Zhong A, He W, Xu H, Forrest CR (1997) Effector mechanism of adenosine in acute ischemic preconditioning of skeletal muscle against infarction. Am J Physiol 273:R887–R895PubMedGoogle Scholar
  6. 6.
    Obermaier R, von Dobschuetz E, Drognitz O, Hopt UT, Benz S (2004) Ischemic preconditioning attenuates capillary no-reflow and leukocyte adherence in postischemic pancreatitis. Langenbecks Arch Surg 389:511–516PubMedCrossRefGoogle Scholar
  7. 7.
    Glazier SS, O'Rourke DM, Graham DI, Welsh FA (1994) Induction of ischemic tolerance following brief focal ischemia in rat brain. J Cereb Blood Flow Metab 14:545–553PubMedGoogle Scholar
  8. 8.
    Sakurai M, Hayashi T, Abe K, Aoki M, Sadahiro M, Tabayashi K (1998) Enhancement of heat shock protein expression after transient ischemia in the preconditioned spinal cord of rabbits. J Vasc Surg 27:720–725PubMedCrossRefGoogle Scholar
  9. 9.
    Turman MA, Bates CM (1997) Susceptibility of human proximal tubular cells to hypoxia: effect of hypoxic preconditioning and comparison to glomerular cells. Ren Fail 19:47–60PubMedCrossRefGoogle Scholar
  10. 10.
    Du ZY, Hicks M, Winlaw D, Spratt P, Macdonald P (1996) Ischemic preconditioning enhances donor lung preservation in the rat. J Heart Lung Transplant 15:1258–1267PubMedGoogle Scholar
  11. 11.
    Li Y, Roth S, Laser M, Ma JX, Crosson CE (2003) Retinal preconditioning and the induction of heat-shock protein 27. Invest Ophthalmol Vis Sci 44:1299–1304PubMedCrossRefGoogle Scholar
  12. 12.
    Hotter G, Closa D, Prados M et al (1996) Intestinal preconditioning is mediated by a transient increase in nitric oxide. Biochem Biophys Res Commun 222:27–32PubMedCrossRefGoogle Scholar
  13. 13.
    Aksoyek S, Cinel I, Avlan D et al (2002) Intestinal ischemic preconditioning protects the intestine and reduces bacterial translocation. Shock 18:476–480PubMedCrossRefGoogle Scholar
  14. 14.
    Cinel I, Avlan D, Cinel L et al (2003) Ischemic preconditioning reduces intestinal epithelial apoptosis in rats. Shock 19:588–592PubMedCrossRefGoogle Scholar
  15. 15.
    Sola A, De Oca J, Gonzalez R et al (2001) Protective effect of ischemic preconditioning on cold preservation and reperfusion injury associated with rat intestinal transplantation. Ann Surg 234:98–106PubMedCrossRefGoogle Scholar
  16. 16.
    Vlasov TD, Smirnov DA, Nutfullina GM (2002) Preconditioning of the small intestine to ischemia in rats. Neurosci Behav Physiol 32:449–453PubMedCrossRefGoogle Scholar
  17. 17.
    Wu B, Ootani A, Iwakiri R et al (2004) Ischemic preconditioning attenuates ischemia–reperfusion-induced mucosal apoptosis by inhibiting the mitochondria-dependent pathway in rat small intestine. Am J Physiol Gastrointest Liver Physiol 286:G580–G587PubMedCrossRefGoogle Scholar
  18. 18.
    Ferencz A, Szanto Z, Borsiczky B et al (2002) The effects of preconditioning on the oxidative stress in small-bowel autotransplantation. Surgery 132:877–884PubMedCrossRefGoogle Scholar
  19. 19.
    Mallick IH, Yang W, Winslet MC, Seifalian AM (2005) Ischaemic preconditioning improves microvascular perfusion and oxygenation following reperfusion injury of the intestine. Br J Surg 92:1169–1176PubMedCrossRefGoogle Scholar
  20. 20.
    Mallick IH, Yang W, Winslet MC, Seifalian AM (2005) Protective effects of ischemic preconditioning on the intestinal mucosal microcirculation following ischemia–reperfusion of the intestine. Microcirculation 12:615–625PubMedCrossRefGoogle Scholar
  21. 21.
    Mallick IH, Yang W, Winslet MC, Seifalian AM (2004) Ischemia–reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 49:1359–1377PubMedCrossRefGoogle Scholar
  22. 22.
    Reddy GK, Enwemeka CS (1996) A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 29:225–229PubMedCrossRefGoogle Scholar
  23. 23.
    Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN (1970) Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 101:478–483PubMedGoogle Scholar
  24. 24.
    Thornton FJ, Barbul A (1997) Healing in the gastrointestinal tract. Surg Clin North Am 77:549–573PubMedCrossRefGoogle Scholar
  25. 25.
    Schroder W, Stippel D, Gutschow C, Leers J, Holscher AH (2004) Postoperative recovery of microcirculation after gastric tube formation. Langenbecks Arch Surg 389:267–271PubMedCrossRefGoogle Scholar
  26. 26.
    Lorentz T, Fok M, Wong J (1989) Anastomotic leakage after resection and bypass for esophageal cancer: lessons learned from the past. World J Surg 13:472–477PubMedCrossRefGoogle Scholar
  27. 27.
    Sekido M, Yamamoto Y, Minakawa H et al (2003) Use of the “supercharge” technique in esophageal and pharyngeal reconstruction to augment microvascular blood flow. Surgery 134:420–424PubMedCrossRefGoogle Scholar
  28. 28.
    Akiyama S, Kodera Y, Sekiguchi H et al (1998) Preoperative embolization therapy for esophageal operation. J Surg Oncol 69:219–223PubMedCrossRefGoogle Scholar
  29. 29.
    Akiyama S, Ito S, Sekiguchi H et al (1996) Preoperative embolization of gastric arteries for esophageal cancer. Surgery 120:542–546PubMedCrossRefGoogle Scholar
  30. 30.
    Kologlu M, Yorganci K, Renda N, Sayek I (2000) Effect of local and remote ischemia–reperfusion injury on healing of colonic anastomoses. Surgery 128:99–104PubMedCrossRefGoogle Scholar
  31. 31.
    Tireli GA, Salman T, Ozbey H, Abbasoglu L, Toker G, Celik A (2003) The effect of pentoxifylline on intestinal anastomotic healing after ischemia. Pediatr Surg Int 19:88–90PubMedGoogle Scholar
  32. 32.
    Posma LA, Bleichrodt RP, van Goor H, Hendriks T (2007) Transient profound mesenteric ischemia strongly affects the strength of intestinal anastomoses in the rat. Dis Colon Rectum 50:1070–1079PubMedCrossRefGoogle Scholar
  33. 33.
    Siemonsma MA, de Hingh IH, de Man BM, Lomme RM, Verhofstad AA, Hendriks T (2003) Doxycycline improves wound strength after intestinal anastomosis in the rat. Surgery 133:268–276PubMedCrossRefGoogle Scholar
  34. 34.
    Jonsson K, Jiborn H, Zederfeldt B (1987) Collagen metabolism in small intestinal anastomosis. Am J Surg 154:288–291PubMedCrossRefGoogle Scholar
  35. 35.
    Brasken P (1991) Healing of experimental colon anastomosis. Eur J Surg Suppl 566:1–51PubMedGoogle Scholar
  36. 36.
    Brasken P, Renvall S, Sandberg M (1991) Fibronectin and collagen gene expression in healing experimental colonic anastomoses. Br J Surg 78:1048–1052PubMedCrossRefGoogle Scholar
  37. 37.
    Pasupathy S, Homer-Vanniasinkam S (2005) Ischaemic preconditioning protects against ischaemia/reperfusion injury: emerging concepts. Eur J Vasc Endovasc Surg 29:106–115PubMedCrossRefGoogle Scholar
  38. 38.
    Sileri P, Sica G, Gentileschi P et al (2004) Ischemic preconditioning protects intestine from prolonged ischemia. Transplant Proc 36:283–285PubMedCrossRefGoogle Scholar
  39. 39.
    Ishida T, Yarimizu K, Gute DC, Korthuis RJ (1997) Mechanisms of ischemic preconditioning. Shock 8:86–94PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Goran Marjanovic
    • 1
  • Eva Jüttner
    • 2
  • Axel zur Hausen
    • 2
  • Ulrich Theodor Hopt
    • 1
  • Robert Obermaier
    • 1
  1. 1.Department of General and Digestive SurgeryUniversity of FreiburgFreiburg im BreisgauGermany
  2. 2.Institute of PathologyUniversity of FreiburgFreiburg im BreisgauGermany

Personalised recommendations