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Effects of Ischemic Precondition and K-ATP Channel Opener Pinacidil on Intestinal Ischemia-Reperfusion Injury

Year 2009, Volume: 3 Issue: 1, 7 - 14, 19.03.2009

Abstract

To investigate and to compare the effect of ischemic precondition and K-ATP channel activating agent pinacidil, showing anti-ischemic effects which are similar to ischemic pre-conditioning, on ischemic injury in experimental intestinal ischemia reperfusion model. Five groups were made up each including 6 Wistar Albino rat (200- 250 gr). Only laparotomy performed on the control group (group I). In I/R (group II), ischemia was induced with vascular clempage for 40 minutes to proximal superior mesentric artery, and then reperfusion was induced for 90 minutes with declampage. Five minutes before I/R period, 0,1 mg/kg pinacidil was given intravenously to Pin.+I/R (group III), in addition to group II. In IÖ+IR group (group IV), before I/R period, 10 minutes ischemia and then 10 minutes reperfusion was performed, in addition to group II. At the fifth minute of the reperfusion stage. Pin. were given to IÖ+Pin.+1/R group (group V), in addition to group IV. The level of malondialdehit (MDA) was measured in blood and terminal ileum tissue by performing relaparatomy. Furthermore, microbiological study was carried out in blood and mesentric lymph node. Histopathologically terminal ileum in the groups was investigated. Bacterial translocation (BT) to MLN and the level of tissue MDA in the I/R group were significantly higher than the other grups. In the IÖ+IR group, BT to MLN, levels of tissue and plasma MDA were significantly lower than I/R group. In the Pin.+I/R group, BT to MLN, level of tissue MDA were significantly lower than I/R group. In the IÖ+Pin.+1/R group, BT to MLN, level of tissue MDA, and histopathologically ileal ischemia score were significantly lower than I/R group. There was no significant difference in the parameters among IÖ+I/R, Pin.+I/R and IÖ+Pin. I/R groups. Pin. and IÖ decreased lipid peroxidation, deterioration in ileum morphology, and BT, resulting from intestinal I/R. Given Pin. and IO together has no superiority on giving them each alone.

References

  • 1. Xu DZ, Lu Q, Kubicka R, Deitch EA. The effect of hypoxia/reoxgenation on the cellular function of intestinal epithelial cells. J Trauma: Injury, Infection and Critical Care 1999; 46: 280-5.
  • 2. Boros M, Kaszaki J, Nagy S. Histamine release during intestinal ischemia-reperfusion: role of ironi ions and hydrogen peroxide. Circ Shock 1991; 35:174-80.
  • 3. Harun E, Dursun D, Ender S. iskemik önkoşullanma. Anadolu Kardiyol Derg. 2003; 3: 144-9.
  • 4. Downey JM, Cohen MV. Arguments is favor of protein kinase C playing an important role in ischemic preconditioning. Basic Res Cardiol 1997; 92: 37-9.
  • 5. Nishizuka Y. Intracellular signalling by hydrolysis of phospholipids and activation of protein kinase C. Science 1992; 258:607-14.
  • 6. Mei DA,Elliott GT, Gross GJ. KATP channels mediate late preconditioning against infarction produced by monophosphoryl lipid A. Am J Physiol 1996; (6Pt2): H2723-9.
  • 7. Chaudry IH. Cellular mechanisms in shock and ischemia and their correction. Am J Physiol 1983; 245: R117-34.
  • 8. Steenbergen C, Fralix T, Murphy E: Role of increased cytosolic calcium concentration myocardial ischemic injury. Basic Res Cardiol 1993;88: 456-63.
  • 9. Grover GJ, Me Cullough JR, Henry DE, Conder ML, Sleph PG. Anti-ischemic effects of the potassium channel activators pinacidil and cromacalim and the reversal of these effects with the potassium channel blocker glyburide. J Pharmacol Exp Ther 1989; 251: 98-104.
  • 10. Grover GJ, Dzwonczyk S, Parham C, Sleph PG. The protective effects of cromakalim and pinacidil on reperfusion function and infarct size in isolated perfused rat hearts and anesthetized dogs. Cardiovasc Drugs Ther 1990; 4: 465-74.
  • 11. Das B, Sarkar C. Cardiomyocyte mitochondrial KATP channels participate the antiarrhy-thmic and antiinfarct effects of KATP activators during ischemia and reperfusion in an intact anesthetized rabit model. Pol J Pharmacol 2003; 55: 771-86.
  • 12. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970; 101: 478-83.
  • 13. Hunter Ml, Nlemadim BC, Davidson DL. Lipid peroxidation products and antioxidant protein in plasma and cerebrospinal from multiple sclerosis patients. Neurochem Res 1985; 10: 1645-52.
  • 14. Mihara M, Uchiyama M. Determination of mal-onaldehyde precursor in tissues by thiobarbituric acid test. Analytical Biochemistry 1978; 86:271-8.
  • 15. Lowry O.H. Protein measurement with the folin phenol reagent. J. Biol Chern 1951 ;193: 265-75.
  • 16. Parks DA, Granger DN. Xanthine oxidase: biochemistry, distribution and physiology. Acta Physiol Scand 1986; 548: 87-99.
  • 17. Zager RA, Baltes LA, Sharma HM, Jurkowitz MS. Responses of the ischemic acute renal failure kidney to additional ischemic events. Kidney Int 1984; 26: 689-700.
  • 18. Yellon DM, Alkhulaifi A, Pugsley Wb. Preconditioning the human myocardium. Lancet 1993; 342: 276-77.
  • 19. Sileri P, Sica G , Gentileschi P et al. Ischemic preconditioning protects intestine from prolonged ischemia. Tranplantation Proceedings 2004; 36: 283-5.
  • 20. Tanno M, Miura T, Tsuchida A et al. Contribution of both the sarcolemmal KATP and mitochondrial KATP channels to infarct size limitation by KATP cahannel openers:diffe-rences from preconditioning in the role of preconditioning. Arch Pharmacol 2001; 364: 226-32.
  • 21. Carrico JC, Meakins JL, Marshall JC, Fry D, Maier RV. Multiple organ failure syndrome. Arc Surg 1986; 121:196-208.
  • 22. Miner TJ, Tavaf-Motamen H, Stojadinovic A, Shea-Donohue T. Ischemia-reperfusion protects the rat small intestine against subsequent injury. J Surg Res 1999; 82:1-10.
  • 23. Aksöyek S, Cinel I, Avlan D et al. Intestinal ischemic preconditioning protects the intestine and reduces bacterial translocation. Shock 2002; 18: 476-80.
  • 24. Basaga HS. Biochemical aspects of free radicals. Biochem Cell Biol 1990; 68: 989-98.
  • 25. Cinel I, Avlan D, Cinel L et al. Ischemic preconditioning recudes intestinal epithelial apoptosis in rats. Shock 2003;19:588-92.

İskemik Önkoşullanmanın ve K-ATP Kanal Açıcı Ajan Pinacidil’in Intestinal İskemi-Reperfüzyon Hasarına Etkisi

Year 2009, Volume: 3 Issue: 1, 7 - 14, 19.03.2009

Abstract

Deneysel intestinal iskemi-reperfüzyon (I/R) modelinde, iskemik önkoşullanmanın (IÖ) ve K-ATP kanallarını spesifik olarak açarak önkoşullanmaya benzer antiiskemik etki gösteren pinacidil’in (Pin.) iskemik hasar üzerine etkilerini incelemek ve karşılaştırmaktır. Her biri 6 Wistar Albino rat (200- 250 gram) içeren 5 grup oluşturuldu. Kontrol (I. grup) grubuna sadece laparotomi yapıldı. I/R (II. grup) grubuna süperior mezenterik arterin aort çıkışına 40 dakika vasküler klempaj ile iskemi yapılıp, ardından klemp açılarak 90 dakika reperfüzyon sağlandı. Pin.+I/R (III. grup) grubuna II. gruba ek olarak I/R periyodundan 5 dakika önce 0.1 mg/kg pinacidil in-travenöz (İV) puşe olarak yapıldı. IÖ+IR (IV. grup) grubuna II. gruba ek olarak I/R periyodundan önce 10 dakika iskemi, 10 dakika reperfüzyon yapıldı. IÖ+Pin.+I/R (V. grup) grubuna IV. gruba ek olarak lÖ’nın reperfüzyon safhasının 5. dakikasında pinacidil uygulandı. Yeniden laparatomi yapılarak kanda ve terminal ileum dokusunda malondialdehit (MDA) düzeyine bakıldı. Kanda ve mezenterik lenf nodu (MLN)’da mikrobiyolojik çalışma yapıldı. Terminal ileum dokusu histopatolojik olarak incelendi. I/R grubunda MLN’e bakteriyel translokasyon (BT)’un ve doku MDA düzeyinin diğer gruplardan yüksek olması istatistiksel olarak anlamlı bulundu. IÖ+IR grubunda MLN’e BT, doku ve serum MDA düzeyleri I/R grubundan anlamlı olarak daha düşüktü. Pin.+I/R grubunda MLN’e BT ve doku MDA düzeyi I/R grubundan anlamlı olarak daha düşük bulundu. IÖ+Pin.+I/R grubunda MLN’e BT’nin, doku MDA düzeyinin ve terminal ileum histopatolojik skorlamasının I/R grubundan anlamlı olarak daha düşük olduğu görüldü. IÖ+I/R, Pin.+I/R ve lÖ+Pin. I/R grupları arasında yukarıdaki parametrelerde anlamlı farklılık saptanmadı. Pin. ve IÖ, intestinal I/R sonucu gelişen lipit peroksidasyonunu, ileum morfolojisindeki bozulmayı ve BT’i azaltmaktadır. Pin. ve îö’nın birlikte kullanılmasının, yalnız Pin. ya da yalnız IÖ ile sağlanan korumaya belirgin bir üstünlüğü yoktur.

References

  • 1. Xu DZ, Lu Q, Kubicka R, Deitch EA. The effect of hypoxia/reoxgenation on the cellular function of intestinal epithelial cells. J Trauma: Injury, Infection and Critical Care 1999; 46: 280-5.
  • 2. Boros M, Kaszaki J, Nagy S. Histamine release during intestinal ischemia-reperfusion: role of ironi ions and hydrogen peroxide. Circ Shock 1991; 35:174-80.
  • 3. Harun E, Dursun D, Ender S. iskemik önkoşullanma. Anadolu Kardiyol Derg. 2003; 3: 144-9.
  • 4. Downey JM, Cohen MV. Arguments is favor of protein kinase C playing an important role in ischemic preconditioning. Basic Res Cardiol 1997; 92: 37-9.
  • 5. Nishizuka Y. Intracellular signalling by hydrolysis of phospholipids and activation of protein kinase C. Science 1992; 258:607-14.
  • 6. Mei DA,Elliott GT, Gross GJ. KATP channels mediate late preconditioning against infarction produced by monophosphoryl lipid A. Am J Physiol 1996; (6Pt2): H2723-9.
  • 7. Chaudry IH. Cellular mechanisms in shock and ischemia and their correction. Am J Physiol 1983; 245: R117-34.
  • 8. Steenbergen C, Fralix T, Murphy E: Role of increased cytosolic calcium concentration myocardial ischemic injury. Basic Res Cardiol 1993;88: 456-63.
  • 9. Grover GJ, Me Cullough JR, Henry DE, Conder ML, Sleph PG. Anti-ischemic effects of the potassium channel activators pinacidil and cromacalim and the reversal of these effects with the potassium channel blocker glyburide. J Pharmacol Exp Ther 1989; 251: 98-104.
  • 10. Grover GJ, Dzwonczyk S, Parham C, Sleph PG. The protective effects of cromakalim and pinacidil on reperfusion function and infarct size in isolated perfused rat hearts and anesthetized dogs. Cardiovasc Drugs Ther 1990; 4: 465-74.
  • 11. Das B, Sarkar C. Cardiomyocyte mitochondrial KATP channels participate the antiarrhy-thmic and antiinfarct effects of KATP activators during ischemia and reperfusion in an intact anesthetized rabit model. Pol J Pharmacol 2003; 55: 771-86.
  • 12. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970; 101: 478-83.
  • 13. Hunter Ml, Nlemadim BC, Davidson DL. Lipid peroxidation products and antioxidant protein in plasma and cerebrospinal from multiple sclerosis patients. Neurochem Res 1985; 10: 1645-52.
  • 14. Mihara M, Uchiyama M. Determination of mal-onaldehyde precursor in tissues by thiobarbituric acid test. Analytical Biochemistry 1978; 86:271-8.
  • 15. Lowry O.H. Protein measurement with the folin phenol reagent. J. Biol Chern 1951 ;193: 265-75.
  • 16. Parks DA, Granger DN. Xanthine oxidase: biochemistry, distribution and physiology. Acta Physiol Scand 1986; 548: 87-99.
  • 17. Zager RA, Baltes LA, Sharma HM, Jurkowitz MS. Responses of the ischemic acute renal failure kidney to additional ischemic events. Kidney Int 1984; 26: 689-700.
  • 18. Yellon DM, Alkhulaifi A, Pugsley Wb. Preconditioning the human myocardium. Lancet 1993; 342: 276-77.
  • 19. Sileri P, Sica G , Gentileschi P et al. Ischemic preconditioning protects intestine from prolonged ischemia. Tranplantation Proceedings 2004; 36: 283-5.
  • 20. Tanno M, Miura T, Tsuchida A et al. Contribution of both the sarcolemmal KATP and mitochondrial KATP channels to infarct size limitation by KATP cahannel openers:diffe-rences from preconditioning in the role of preconditioning. Arch Pharmacol 2001; 364: 226-32.
  • 21. Carrico JC, Meakins JL, Marshall JC, Fry D, Maier RV. Multiple organ failure syndrome. Arc Surg 1986; 121:196-208.
  • 22. Miner TJ, Tavaf-Motamen H, Stojadinovic A, Shea-Donohue T. Ischemia-reperfusion protects the rat small intestine against subsequent injury. J Surg Res 1999; 82:1-10.
  • 23. Aksöyek S, Cinel I, Avlan D et al. Intestinal ischemic preconditioning protects the intestine and reduces bacterial translocation. Shock 2002; 18: 476-80.
  • 24. Basaga HS. Biochemical aspects of free radicals. Biochem Cell Biol 1990; 68: 989-98.
  • 25. Cinel I, Avlan D, Cinel L et al. Ischemic preconditioning recudes intestinal epithelial apoptosis in rats. Shock 2003;19:588-92.
There are 25 citations in total.

Details

Primary Language Turkish
Subjects General Surgery
Journal Section Research Article
Authors

Saadet Akturan This is me

Publication Date March 19, 2009
Published in Issue Year 2009 Volume: 3 Issue: 1

Cite

APA Akturan, S. (2009). İskemik Önkoşullanmanın ve K-ATP Kanal Açıcı Ajan Pinacidil’in Intestinal İskemi-Reperfüzyon Hasarına Etkisi. Turkish Medical Journal, 3(1), 7-14.

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