Protective effects of cilostazol and levosimendan on lung injury induced by lower limb ischemia-reperfusion

Amaç: Bu çalışmada, abdominal aort cerrahisinde iskemi/ reperfüzyon (İ/R) sonrası uzak organ hasarı olarak akciğer üzerine silostazol, levosimendan ve bu ilaçların kombinasyonunun etkileri araştırıldı. Çalışma planı: Çalışma ortalama 219±26 g ağırlığında 35 erkek Wistar albino türü sıçan ile gerçekleştirildi. Sıçanlar her bir grupta yedi sıçan olacak şekilde randomize olarak beş gruba ayrıldı. Sıçanlara silostazol, levosimendan ve bu iki ilacın kombinasyonu ile tedavi uygulandıktan sonra, infrarenal aortik oklüzyon ile alt ekstremitelere 120 dakika iskemi ve sonrasında 60 dakika reperfüzyon uygulandı. Sıçanlar derin anestezi altında sakrifiye edildi ve akciğer dokuları çıkarıldı. Akciğer dokularında malondialdehid (MDA) düzeyleri, süperoksit dismutaz (SOD) aktiviteleri ve glutatyon (GSH) düzeyleri ölçüldü. Doku örnekleri ayrıca ışık mikroskobu ile histopatolojik olarak incelendi. Bulgular: Çalışmada İ/R’nin akciğer dokusunda MDA düzeylerini yükseltirken, SOD aktivitesini ve GSH düzeylerini azalttığı belirlendi (p

Alt ekstremite iskemi reperfüzyonuna bağlı akciğer hasarında silostazol ve levosimendanın koruyucu etkisi

Background: In this study, we aimed to investigate the effects of cilostazol and levosimendan, and the combination of these agents on the lung remote organ damage after ischemia/reperfusion (I/R) following abdominal aortic surgery. Methods: The experiments were performed on 35 male Wistar albino rats weighing mean 219±26 g. The rats were randomly assigned into five groups, including each of seven rats. Rats were pretreated with cilostazol and levosimendan, alone or in combination, and then lower extremities were subjected to I/R induced by a infrarenal aortic occlusion for duration of 120 minutes, followed by a-60 minute- reperfusion. The rats were sacrificed under deep anesthesia and the lung tissues were removed. Malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and glutathione (GSH) levels were measured in the lung tissues. The tissue samples were further examined histopathologically under light microscopy. Results: It was found that I/R elevated MDA levels accompanied by a reduction in SOD activities and GSH levels (p

___

  • 1. Akar H, Saraç A, Konuralp C, Yildiz L, Kolbakir F. Comparison of histopathologic effects of carnitine and ascorbic acid on reperfusion injury. Eur J Cardiothorac Surg 2001;19:500-6.
  • 2. Welbourn R, Goldman G, O’Riordain M, Lindsay TF, Paterson IS, Kobzik L, et al. Role for tumor necrosis factor as mediator of lung injury following lower torso ischemia. J Appl Physiol 1991;70:2645-9.
  • 3. Aoki C, Hattori Y, Tomizawa A, Jojima T, Kasai K. Antiinflammatory role of cilostazol in vascular smooth muscle cells in vitro and in vivo. J Atheroscler Thromb 2010;17:503-9.
  • 4. Kawamura K, Fujita S, Tani T, Kimura Y. Effect of cilostazol, a new antithrombotic drug, on an experimental model of peripheral circulation insufficiency. Arzneimittelforschung 1985;35:1154-6.
  • 5. Liu Y, Shakur Y, Yoshitake M, Kambayashi Ji J. Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc Drug Rev 2001;19:369-86.
  • 6. Shinohara Y, Gotoh F, Tohgi H, Hirai S, Terashi A, Fukuuchi Y, et al. Antiplatelet cilostazol is beneficial in diabetic and/ or hypertensive ischemic stroke patients. Subgroup analysis of the cilostazol stroke prevention study. Cerebrovasc Dis 2008;26:63-70.
  • 7. Hattori Y, Suzuki K, Tomizawa A, Hirama N, Okayasu T, Hattori S, et al. Cilostazol inhibits cytokine-induced nuclear factor-kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Cardiovasc Res 2009;81:133-9.
  • 8. Follath F, Cleland JG, Just H, Papp JG, Scholz H, Peuhkurinen K, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002;360:196-202.
  • 9. Parissis JT, Adamopoulos S, Antoniades C, Kostakis G, Rigas A, Kyrzopoulos S, et al. Effects of levosimendan on circulating pro-inflammatory cytokines and soluble apoptosis mediators in patients with decompensated advanced heart failure. Am J Cardiol 2004;93:1309-12.
  • 10. Erbüyün K, Vatansever S, Tok D, Ok G, Türköz E, Aydede H, et al. Effects of levosimendan and dobutamine on experimental acute lung injury in rats. Acta Histochem 2009;111:404-14.
  • 11. Yasa H, Yakut N, Emrecan B, Ergunes K, Ortac R, Karahan N, et al. Protective effects of levosimendan and iloprost on lung injury induced by limb ischemia-reperfusion: a rabbit model. J Surg Res 2008;147:138-42.
  • 12. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
  • 13. Winterbourn CC, Hawkins RE, Brian M, Carrell RW. The estimation of red cell superoxide dismutase activity. J Lab Clin Med 1975;85:337-41.
  • 14. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979;582:67-78.
  • 15. Francischetti I, Moreno JB, Scholz M, Yoshida WB. Leukocytes and the inflammatory response in ischemiareperfusion injury. Rev Bras Cir Cardiovasc 2010;25:575-84. [Abstract]
  • 16. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995;41:1819-28.
  • 17. Işlekel H, Işlekel S, Güner G, Ozdamar N. Evaluation of lipid peroxidation, cathepsin L and acid phosphatase activities in experimental brain ischemia-reperfusion. Brain Res 1999;843:18-24.
  • 18. Koca K, Yurttaş Y, Yıldız C, Caycı T, Uysal B, Korkmaz A. Effect of hyperbaric oxygen and ozone preconditioning on oxidative/nitrosative stress induced by tourniquet ischemia/ reperfusion in rat skeletal muscle. Acta Orthop Traumatol Turc 2010;44:476-83. doi: 10.3944/AOTT.2010.2327.
  • 19. Chan SC, Hanifin JM. Differential inhibitor effects on cyclic adenosine monophosphate-phosphodiesterase isoforms in atopic and normal leukocytes. J Lab Clin Med 1993;121:44-51.
  • 20. Kim KY, Shin HK, Choi JM, Hong KW. Inhibition of lipopolysaccharide-induced apoptosis by cilostazol in human umbilical vein endothelial cells. J Pharmacol Exp Ther 2002;300:709-15.
  • 21. Lee JH, Oh GT, Park SY, Choi JH, Park JG, Kim CD, et al. Cilostazol reduces atherosclerosis by inhibition of superoxide and tumor necrosis factor-alpha formation in lowdensity lipoprotein receptor-null mice fed high cholesterol. J Pharmacol Exp Ther 2005;313:502-9.
  • 22. O'Donnell ME, Badger SA, Sharif MA, Makar RR, McEneny J, Young IS, et al. The effects of cilostazol on exercise-induced ischaemia-reperfusion injury in patients with peripheral arterial disease. Eur J Vasc Endovasc Surg 2009;37:326-35.
  • 23. Kaheinen P, Pollesello P, Levijoki J, Haikala H. Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels. J Cardiovasc Pharmacol 2001;37:367-74.
  • 24. Antoniades C, Tousoulis D, Koumallos N, Marinou K, Stefanadis C. Levosimendan: beyond its simple inotropic effect in heart failure. Pharmacol Ther 2007;114:184-97.
  • 25. Trikas A, Antoniades C, Latsios G, Vasiliadou K, Karamitros I, Tousoulis D, et al. Long-term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure. Eur J Heart Fail 2006;8:804-9.
Türk Göğüs Kalp Damar Cerrahisi Dergisi-Cover
  • ISSN: 1301-5680
  • Yayın Aralığı: 4
  • Başlangıç: 1991
  • Yayıncı: Bayçınar Tıbbi Yayıncılık
Sayıdaki Diğer Makaleler

An absent right superior vena cava with a persistent left superior vena cava combined with the presence of a ventricular septal defect in a pediatric patient: Implications for surgical correction

Murat GÜVENER, Orhan Saim DEMİRTÜRK, Mediha Hacer ÜlGER, Ayten GÜMÜŞ

Thoracoscopy under local anesthesia for patients with a high cardiopulmonary risk index

Gökhan YUNCU, Cansel ATINKAYA, Figen TÜRK, Tolga SEMERKANT, Göksel KITER

Obstrüktif hipertrofik kardiyomiyopatide cerrahi tedavinin erken ve orta dönem sonuçları

Cemal Levent BİRİNCİOĞLU, Anıl ÖZEN, Ertekin Utku ÜNAL, Hakkı Zafer İŞCAN

İzole koroner arter baypas graft cerrahisi sonrası geçici pace telleri gerekli midir?

Muhammet Onur HANEDAN, Adnan YALÇINKAYA, Emre YAŞAR, Ersin KADİROĞULLARI, Garip ALTINTAŞ, Serkan MOLA, Mehmet Ali ÖZATİK, Adem İlkay DİKEN

Hipertrofik obstrüktif kardiyomiyopatide septal alkol ablasyonu: Retrospektif bir inceleme

Evrim ŞİMŞEK, Cemil GÜRGÜN, Can HASDEMİR, Levent Hürkan CAN, Oğuz YAVUZGİL, Serdar PAYZIN, Cüneyt TÜRKOĞLU, Kamil TÜLÜCE, Hakan KÜLTÜRSAY

The effect of atrium diameter on the successful treatment of atrial fibrillation through the radiofrequency ablation technique

Tevfik GÜNEŞ, Aykut ŞAHİN, Serdar BAYRAK, Levent YILIK, Mert KESTELLİ, Ali GÜRBÜZ

İki gebe hastada gelişen mekanik kalp kapağı trombozunun düşük molekül ağırlıklı heparin tedavisi ile takibi: Olgu sunumu

Erhan Renan UÇAROĞLU, Erol ŞENER, Levent ÇETİN, Ayşegül KUNT, Mete HIDIROĞLU, Aslıhan KÜÇÜKER

The role of tumor SUVmax/lymph node SUVmax ratio viewed on PET-CT in the detection of mediastinal metastasis in patients with lung cancer

Selahattin ÖZTAŞ, Müge ÖZDEMİR, Güliz ATAÇ, Melahat KURUTEPE, Özlen TÜMER, Yelda TEZEL, Eylem ACARTÜRK, Ali Vefa ÖZTÜRK, Gül ERDAL

A simple method for eliminating strain on aortocoronary saphenous vein bypass grafts: The suspension of the right atrial appendage and plication of the right atrium

Kenan SEVER, Denyan MANSUROĞLU, Nuri KURTOĞLU, İsmail Cihan ÖZBEK

Tracheoinnominate artery fistula in a pediatric patient with idiopathic scoliosis

Barış ÇAYNAK, Emine OKLU, Belhhan AKPINAR, Burak ONAN, İsmihan Selen ONAN