The Effects of Ischemic Preconditioning on Cardiac Ischemia-Reperfusion Injury in Rat Lung

Öz

Ischemia and reperfusion of a tissue or a viscera may also show 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. In this study, we have investigated the effects of preconditioning induced by pulmonary artery occlusion on myocardial ischemia and ischemia- reperfusion injury on a rat model. For this purpose, we used adult, in both sex , 30 Sprague-Dawley rats (n=6). There were five experimental groups; Group 1: Control (Sham operated), Group 2: 30 minute myocardial ischemia induced by left coronary artery occlusion, Group 3: 30 minute left coronary artery occlusion followed by 60 minute reperfusion, Group 4: Pulmonary ischemic preconditioning followed by 30 minute left coronary artery occlusion, Group 5: Pulmonary ischemic preconditioning followed by 30 minute left coronary artery occlusion and 60 minute reperfusion. Malonyldialdehyde and purine nucleotide levels of myocardial tissue were measured by high performance liquid chromatography. As a conclusion, remote preconditioning evoked by pulmonary artery occlusion and reperfusion may induce a protective effect against myocardial ischemia and ischemia- reperfusion injury. It can be suggested that the protective effect of remote preconditioning is related with myocardial adenosine.

Anahtar Kelimeler

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

Sıçan Akciğerinde Oluşturulan İskemik Önkoşullamanın Kalpteki İskemi Reperfüzyon Hasarı Üzerine Etkileri

Öz

Bir organ veya dokunun iskemi ve reperfüzyonu ile oluşturulan önkoşullama, başka bir arterin beslediği organ veya dokuyu da önkoşullayarak koruyucu etki gösterebilir. Bu durum uzak iskemik önkoşullama olarak adlandırılır. Biz bu çalışmamızda sıçan akciğerinde oluşturduğumuz önkoşullamanın kalpteki 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: Kalpte iskemi (30 dk), Grup 3: Kalpte iskemi (30 dk)-reperfüzyon (60 dk), Grup 4: Akciğerde iskemik önkoşullama sonrası kalpte iskemi (30 dk), Grup 5: Akciğerde iskemik önkoşullama sonrası kalpte iskemi (30 dk)-reperfüzyon (60 dk). Deney sonrası aldığımız sol kalp doku örneklerinde yüksek performanslı likit kromatografi kullanarak malondialdehid ile pürin nükleotid düzeylerini analiz ettik. Sonuç olarak, akciğerde oluşturulan iskemik önkoşullamanın kalpteki iskemi ve iskemireperfüzyon 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. Shiki K, Hearse DJ. Preconditioning of ischemic myocardium: reperfusion-induced arrhytmias. Am J Physiol, 1987; 253: H1470- 1476.
3. Kaeffer N, Richard V, Francois A, et al. Preconditioning prevents chronic reperfusion- induced coronary endothelial dysfunction in rats. Am J Physiol, 1996; 271 (3 Pt 2): H842– H49.
4. Bolli R. The late phase of preconditioning. Circ Res, 2000; 87: 972-983.
5. Schulz R, Cohen MV, Behrends M, et al. Signal transduction of ischemic preconditioning. Cardiovasc Res, 2001; 52: 181-198.
6. Demiryürek Ş, Ceylan H, Demiryürek AT. İskemik önkoşullama ve etki mekanizması Genel Tıp Dergisi, 2003; 13: 187-194.
7. Liu GS, Thornton J, Van Winkle DM, et al. Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation, 1991; 84: 350-356.
8. 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: 661–668.

9. Auchampach JA, Gross GJ. Adenosine A1 receptors, KATP channels, and ischemic preconditioning in dogs. American J of Physiology, 1993; 264: 1327–1336.
10. 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:
11. Liauw SK, Rubin BB, Lindsay TF, Romaschin AD, Walker PM. Sequential ischemia/reperfusion results in contralateral skeletal muscle salvage. Am J Physiol, 1996; 270: 1407–1413.
12. Pell TJ, Baxter GF, Yellon DM, Drew GM. Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol, 1998; 275: 1542–1547.
13. Patel HH, Moore J, Hsu KA, Gross GJ. Cardioprotection at a distance: Mesenteric artery occlusion protects the myocardium via an opioid sensitive mechanism. J Mol Cell Cardiol, 2002; 34: 1317-1323
14. Petrishchev NN, Vlasov TD, Sipovsky VG, Kurapeev DI, Galagudza MM. Does nitric oxide generation contribute to the mechanism of remote ischemic preconditioning? Pathophysiology, 2001; 7: 271-274.
15. 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: 1725-1727.
16. 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.
17. Soncul H, Öz E, Kalaycioglu S. Role of Ischemic Preconditioning on Ischemia- Reperfusion Injury of the Lung. Chest,1999; 115: 1672-1677.
18. Buyukates M, Kalaycioglu S, Oz E, Soncul H. Effects of Ischemic Preconditioning in Human Heart. Journal of Cardiac Surgery, 2005; 20: 241-245.
19. 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: 208-215.
20. 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: 781-791.
21. Van Wylen DG. Effect of ischemic preconditioning on interstitial purine metabolite and lactate accumulation during myocardial ischemia. Circulation, 1994; 89: 2283-2289.
22. Harrison GJ, Willis RJ, Headrick JP: Extracellular adenosine levels and cellular energy metabolism in ischemically preconditioned rat heart. Cardiovasculer Research, 1998; 40: 74-87.
23. Weinbrenner C, Nelles M, Herzog N, Sarvary L, Strasser RH. Remote preconditioning by infrarenal occlusion of the aorta protects the heart from infarction: a newly identified non- neuronal but PKC-dependent pathway. Cardiovasc Res, 2002; 55: 590-601.
24. Theresa PJ, Baxter GF, Yellon DM, Drew GM. Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol, 1998; 275: 1542-1547.
25. Takaoka A, Nakae I, Mitsunami K, et al. Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of "remote preconditioning." J Am Coll Cardiol, 1999; 33:
26. De Jonge R, Bradamante S, Speleman L, De Jong W. Carbohydrates and purines in underperfused hearts, protected by ischemic preconditioning. J Mol Cell Cardiol, 1998; 30: 699-708.