The Effects of Remote Ischemic Preconditioning On Pulmonary Ischemia- Reperfusion Injury on a Rat Model

Öz

Ischemia and reperfusion of a tissue or a viscera can induce a protective effect such as development of preconditioning on the other tissues which have another source of arterial blood flow. This mechanism of action is known as remote ischemic preconditioning. The objective of this study was to investigate the effects of preconditioning formed by coronary artery occlusion over the pulmonary ischemia and ischemia-reperfusion injury in a rat model. We used adult, 30 Sprague-Dawley rats (n=6). There were five experimental groups;Group 1: Control (Sham operated), Group 2: Pulmonary ischemia (30 min), Group 3: Pulmonary ischemia (30 min)-reperfusion (60 min), Group 4: Cardiac ischemic preconditioning followed by pulmonary ischemia (30 min), Group 5: Cardiac ischemic preconditioning followed by pulmonary ischemia (30 min)-reperfusion (60 min). In the end of experimental procedures, histopathological assessments were performed on lung tissue specimens and malonyldialdehyde and purine nucleotide levels of lung tissue were measured by High Performance Liquid Chromatography. As a conclusion, cardiac ischemic preconditioning can induce a protective effect over the pulmonary ischemia and ischemia-reperfusion injury. It can be suggested that the protective effect of remote ischemic preconditioning is related with adenosine.

Anahtar Kelimeler

• Rat, Heart, Pulmonary, Remote Ischemic Preconditioning, Adenosine.

Sıçan Modelinde Uzak İskemik Önkoşullamanın Akciğerdeki İskemi Reperfüzyon Hasarı Üzerine Etkileri

Öz

Bir organ veya dokunun iskemi ve reperfüzyonu ile oluşturulan önkoşullama, başka bir arterin beslediği organ veya dokuyu önkoşullayarak koruyucu etki gösterebilir. Bu durum uzak iskemik önkoşullama olarak adlandırılır. Biz de çalışmamızda sıçan kalbinde oluşturduğumuz iskemik önkoşullamanın, akciğerdeki iskemi ve iskemi-reperfüzyon hasarı üzerindeki etkilerini incelemeyi hedefledik. Çalışmamızda 30 adet (n=6) Sprague-Dawley sıçan kullandık. Grupları şu şekilde oluşturduk; Grup 1: Kontrol Grubu (Sham Opere), Grup 2: Akciğerde iskemi (30 dk), Grup 3: Akciğerde iskemi (30 dk)-reperfüzyon (60 dk), Grup 4: Kalpte iskemik önkoşullama sonrası akciğerde iskemi (30 dk), Grup 5: Kalpte iskemik önkoşullama sonrası akciğerde iskemi (30 dk)-reperfüzyon (60 dk). Deney sonrası aldığımız akciğer doku örneklerinde, histopatolojik incelemeler ve yüksek performanslı likit kromatografi cihazı kullanarak malondialdehid ile pürin nükleotid düzeylerini ölçtük. Sonuç olarak kalpte oluşturulan iskemik önkoşullamanın, akciğerdeki iskemi ve iskemi-reperfüzyon hasarı üzerinde koruyucu etkisinin olduğunu ve bu etkinin adenozin ile ilişkili olduğunu söyleyebiliriz.

Anahtar Kelimeler

• Sıçan, Kalp, Akciğer, Uzak İskemik Önkoşullama, Adenozin

Kaynakça

1. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986; 74: 1124-1136.
2. Neely CF, Keith IM. A1 adenosine
3. Ferdinandy P. Preconditioning decreases
4. ischemia/reperfusion-induced peroxynitrite
5. formation. Biochem Biophys Res Commun, 2001; 285: 1217-1219. 1036-1046.
6. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation, 1993; 87(3): 893-899.
7. Lykkesfeldt J. Determination of Malondialdehyde as Dithiobarbituric Acid Adduct in Biological Samples by HPLC with Fluorescence Detection: Comparison with Ultraviolet-Visible Spectrophotometry.Clinical Chemistry, 2001; 47(9): 1725-1727.
8. Volonte MG, Yuln G, Quiroga P, Consolini AE. Development of an HPLC method for determination of metabolic compounds in myocardial tissue. J of Pharmaceutical and Biomedical Analysis, 2004; 35: 647-653.

9. Soncul H, Öz E, Kalaycioglu S. Role of Ischemic Preconditioning on Ischemia- Reperfusion Injury of the Lung. Chest,1999; 115: 1672-1677.
10. Ucar G, Topaloglu E, Kandilci HB, Gumusel B. Effect of ischemic preconditioning on reactive oxygen species-mediated ischemia- -reperfusion injury in the isolated perfused rat lung. Clin Biochem, 2005; 38(7): 681-684.
11. Li G, Chen S, Lu E, Hu T. Protective
12. Li G, Chen S, Lu E, Luo W. Cardiac ischemic preconditioning improves lung preservation in valve replacement operations. Ann Thorac Surg, 2001; 71(2): 631-635.
13. Auchampach JA, Gross GJ. Adenosine A1 receptors, KATP channels, and ischemic preconditioning in dogs. American J of Physiology, 1993; 264: 1327-1336.
14. Altug S, Demiryürek AT, Kane KA, Kanzık İ. Evidence for the involvement of peroxynitrite in ischaemic preconditioning in rat isolated hearts. Br J Pharmacol, 2000; 130: 125-131.
15. Csonka C, Csont T, Onody A,
16. Liu Y, Ytrehus K, Downey JM. Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium. J Mol Cell Cardio, 1994; l 26: 661–8.
17. Kitakaze M, Hori M, Takashima S, et al. Ischemic preconditioning increases adenosine release and 5'-nucleotidase activity during myocardial ischemia and reperfusion in dogs. Implications for myocardial salvage. Circulation, 1993; 87(1): 208-215.
18. Kitakaze M, Node K, Minamino T, et al. Role of activation of protein kinase C in the infarct size-limiting effect of ischemic preconditioning through activation of ecto-5'- nucleotidase. Circulation, 1996; 93(4): 781-791.
19. Van Wylen DG. Effect of ischemic preconditioning on interstitial purine metabolite and lactate accumulation during myocardial ischemia. Circulation, 1994; 89(5): 2283-2289.
20. Harrison GJ, Willis RJ, Headrick JP. Extracellular adenosine levels and cellular energy metabolism in ischemically preconditioned rat heart. Cardiovasculer Research, 1998; 40(1): 74-87.
21. Yildiz G, Demiryurek AT, Gumusel B, Lippton H. Ischemic preconditioning modulates ischemia-reperfusion injury in the rat lung: role of adenosine receptors. Eur J Pharmacol, 2007; 556(1-3): 144-150.
22. Kandilci HB, Gumusel B, Topaloglu E, et al. Effects of ischemic preconditioning on rat lung: role of nitric oxide. Exp Lung Res, 2006; 32(7): 287-303.
23. Kandilci HB, Gumusel B, Demiryurek AT, Lippton H. Preconditioning modulates pulmonary endothelial dysfunction following ischemia-reperfusion injury in the rat lung: role of potassium channels. Life Sci, 2006; 79(23): 2172-2178.
24. Kharbanda RK, Li J, Konstantinov IE, et al. Remote ischaemic preconditioning protects against cardiopulmonary bypass- induced tissue injury: a preclinical study. Heart, 2006; 92(10): 1506-1511.
25. Xia Z, Herijgers P, Nishida T, et al. Remote preconditioning lessens the deterioration of pulmonary function after repeated coronary artery occlusion and reperfusion in sheep. Can J Anaesth, 2003;50(5): 481-488.
26. Peralta C, Prats N, Xaus C, Gelpi E, Rosello-Catafau J. Protective effect of liver ischemic preconditioning on liver and lung injury induced by hepatic ischemia-reperfusion in the rat. Hepatology, 1999; 30(6): 1481-9.
27. Harkin DW, Barros D'Sa AA, McCallion K, Hoper M, Campbell FC. Ischemic preconditioning before lower limb ischemia--reperfusion protects against acute lung injury. J Vasc Surg, 2002; 35(6):1264-73.
28. Ito K, Ozasa H, Kojima N, et al. Pharmacological preconditioning protects lung injury induced by intestinal ischemia / reperfusion in rat. Shock, 2003; 19(5): 462- 468.
29. Glantz L, Avramovich A, Trembovler V, et al. Ischemic preconditioning increases antioxidants in the brain and peripheral organs after cerebral ischemia. Exp Neurol, 2005; 192(1): 117-124.