Koroner Arter Bypass Cerrahisinde Losartan’ın İnternal Torasik Arter, Radial Arter ve Safen Ven Greftlerindeki Nitrik Oksit Düzeyine Etkisi

Amaç: Koroner arter cerrahisinde greft açık kalma süresi endotel fonksiyonuna bağlıdır. Nitrik Oksitin (NO) endotel fonksiyonuna yararlı etkisi bilinmektedir. Greftlerdeki Nitrik Oksit düzeyi ve Losartan’ın Nitrik Oksit üzerine etkisi invitro olarak araştırılmıştır. Yöntem: Çalışma 13 hasta da 78 örnek ile yapıldı. İnternaltorasik arter, radial arter ve safenvengreft örnekleri “Kontrol Grubu” ve “Losartan Grubu” olmak üzere ikiye ayrıldı. Losartan grubu örnekleri 1 x 10-5molar Losantanlı Troyde’s solüsyonu çözeltisi içinde inkübe edildi. Nitrik Oksit, Griess yöntemi kullanılarak ölçüldü. İstatistiksel değerlendirme. Kruskal Wallis Oneway ANOVA, İndependentsample T ile Tukey ve Bonferroni testleri kullanılarak yapıldı. Bulgular: Kontrol grubu bazal Nitrik Oksit değeri, internaltorasik arter greftinde anlamlı olarak yüksek bulunmuştur (p<0,05). Losartan grubu internal torasik arter ve radial arter greftlerinde Nitrik Oksit artışı anlamlı değildir. Sonuç: İnternal torasik arter en uzun açık kalma süresine sahip greftir, çünkü endotelinde Nitrik Oksit düzeyi yüksektir. Spasmolitik ilaçların kullanımı da greft açık kalma süresini olumlu etkiler. Losartan İnternal torasik arter ve radial arterlerde Nitrik Oksit düzeyini artırması olumludur fakat yeni çalışmalarla da desteklenmelidir.

Anahtar Kelimeler:

cabg, losartan, nitrik oksit, greft açıklığı

The Effect of Losartan on the Levels of Nitric Oxide in Internal Thoracic Artery, Radial Artery and Saphenous Ven Grafts in Coronary Artery Bypass Surgery

Objective: Graft exposure time in coronary artery surgery depends on endothelial function. The beneficial effect of nitricoxide on endothelial function is known. Nitricoxide level in grafts and the effect of Losartan on nitricoxide were investigated as in vitro. Methods: The study was carried out with 78 samples in 13 patients. Internal thoracic artery, radial artery and saphenous vein graft samples were divided into "Control Group" and "Losartan Group". Statistical evaluation was performed using Kruskal Wallis Oneway ANOVA, Independent sample T, Tukey and Bonferroni tests. Results: The baseline Nitric Oxide value in the control group was significantly higher in the internal thoracic artery graft (p<0.05). Nitric Oxide increase was not found significant in losartan group internal thoracic artery and radial artery grafts. Coclusion: The internal thoracic artery is the graft with the longest patency; because NitricOxide is high level in endothelial tissue. Theuse of spasmolytic drugs for the patency of the grafts also provides positive use. Nitric Oxide increase is positive in the internal thoracic artery and radial arteries, but it will be supported by new studies.

Keywords:

CABG, graft potency, losartan, nitric oxide,

PDF

___

Cannon RO, Role of nitric oxide in cardiovascular disease: focus on the endothelium. Clinical Chem. 1988;44(2):1809–1819.
Furchgott RF and Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–376. https://doi.org/10.1038/288373a0
Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327(6122):524-526.
Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. PNAS. 1987;84(24), 9265–9269. https://doi.org/10.1073/pnas.84.24.9265
Liu Z, Wildhirt SM, Weismüller S, Schulze C, Conrad N, Reichart B. Nitric oxide and endothelin in the development of cardiac allograft vasculopathy. Potential targets for therapeutic interventions. Atherosclerosis. 1998;140(1),1–14. https://doi.org/10.1016/s0021-9150(98)00106-3.
Luscher TF, Vanhoutte PM. Endothelium. 1990;54. CRC press.
Macdonald PS, Read MA, Dusting GJ. Synergistic inhibition of platelet aggregation by endothelium-derived relaxing factor and prostacyclin. Thrombosis Research. 2001;49(5):437–449. https://doi.org/10.1016/s0049-3848(98)90001-9
Scott-Burden T, Schini VB, Elizondo E, Junquero DC, Vanhoutte PM. Platelet-derived growth factor suppresses and fibroblast growth factor enhances cytokine-induced production of nitric oxide by cultured smooth muscle cells. Effects on cell proliferation. Circulation research. 1992;71(5):1088–1100. https://doi.org/10.1161/01.res.71.5.1088
Moshage H, Kok B, Huizenga JR, Jansen PL. Nitrite and nitrate determinations in plasma: a critical evaluation. Clinical Chem. 1995;41(6):892-896.
Marzinzig M, Nussler AK, Stadler J, Marzinzig E, Barthlen W, Nussler NC, Brückner UB. Improved Methods to Measure End Products of Nitric Oxide in Biological Fluids: Nitrite, Nitrate, andS-Nitrosothiols. Nitric Oxide. 1997;1(2):177-189.
Ignarro L. Physiologic and pathopysiologic signifiance of Nitric Oxide. Textbook of Critical Care, Third Edition. Editor: Scehomaker WC. Textbook of Critical Care Schomaker/ Ayres/ Grenvik/ Hobrook. WB Saunders Company Press, London- New York; 1995:208-225.
Opie LH. The renin-angiotensin-aldosterone system and its role in cardiovascular regulation. Editor: Lionel H. Opie, Angiotensin Converting Enzyme Inhibitors, Third Edition. Auther Publishing House-New York, Universty of Cape Town Press, 1999:1-22.
Griendling KK, Murphy TJ, Alexander RW. Molecular biology of the renin-angiotensin system. Circulation. 1993;87(6):1816-1828.
Voors AA, Pinto YM, Buikema H, Urata H, Oosterga M, Rooks G, Grandjean JG, Ganten D, van Gilst WH. Dual pathway for angiotensin II formation in human internal mammary arteries. British J Pharmacol. 1998;125(5):1028–1032. https://doi.org/10.1038/sj.bjp.0702150
Dzau VJ. Mechanism of protective effects of ACE inhibition on coronary artery disease. European Heart Journal. 1998;19 Suppl J:J2–J6.
Varty K, Allen KE, Jones L, Sayers RD, Bell PR, London NJ. Influence of Losartan, an angiotensin receptor antagonist, on neointimal proliferation in cultured human saphenous vein. The British Journal of Surgery. 1994;81(6):819–822. https://doi.org/10.1002/bjs.1800810609
Borland JA, Chester AH, Crabbe S, Parkerson JB, Catravas JD, Yacoub MH. Differential action of angiotensin II and activity of angiotensin-converting enzyme in human bypass grafts. The Journal of Thoracic and Cardiovascular Surgery, 1998;116(2):206–212. https://doi.org/10.1016/s0022-5223(98)70118-7
Michael AW. Losartan. Editor: Messerelli FH. Cardiovascular Drug Theraphy, Chapter 88, Second Edition. Philadelphia-Pennsylvania. WB Saunders Company; 1996: 817-825.
Cannon RO. Role of nitric oxide in cardiovascular disease: focus on the endothelium. Clinical Chem. 1998;44(8):1809-1819.
van Son JA, Smedts F, Vincent JG, van Lier HJ, Kubat K. Comparative anatomic studies of various arterial conduits for myocardial revascularization. The Journal of Thoracic and Cardiovascular Surgery. 1990;99(4):703–707.
Ellis SG, Brener SJ, DeLuca S, Tuzcu EM, Raymond RE, Whitlow PL, Topol EJ. Late myocardial ischemic events after saphenous vein graft intervention-importance of initially "nonsignificant" vein graft lesions. The American Journal of Cardiology. 1997;79(11):1460–1464. https://doi.org/10.1016/s0002-9149(97)00171-9
Borland JA, Chester AH, Crabbe S, Parkerson JB, Catravas JD, Yacoub MH. Differential action of angiotensin II and activity of angiotensin-converting enzyme in human bypass grafts. The Journal of Thoracic and Cardiovascular Surgery. 1990;116(2):206–212. https://doi.org/10.1016/s0022-5223(98)70118-7
Chester AH, Buttery LD, Borland JA, Springall DR, Rothery S, Severs NJ, Polak JM, Yacoub MH. Structural, biochemical and functional effects of distending pressure in the human saphenous vein: implications for bypass grafting. Coronary Artery Disease. 1998;9(2-3): 143–151.
He GW, Yang CQ. Radial artery has higher receptor-mediated contractility but similar endothelial function compared with mammary artery. The Annals of Thoracic Surgery. 1997;63(5):1346–1352. https://doi.org/10.1016/s0003-4975(97)00106-9
He GW, Liu ZG. Comparison of nitric oxide release and endothelium-derived hyperpolarizing factor-mediated hyperpolarization between human radial and internal mammary arteries. Circulation. 2001;104(12 Suppl 1):I344–I349. https://doi.org/10.1161/hc37t1.094930
Ku DD, Caulfield JB, Kirklin JK. Endothelium-dependent responses in long-term human coronary artery bypass grafts. Circulation. 1991;83(2):402–411. https://doi.org/10.1161/01.cir.83.2.402
Flavahan S, Chang F, Flavahan NA. Local renin-angiotensin system mediates endothelial dilator dysfunction in aging arteries. American Journal of Physiology. Heart and Circulatory Physiology. 2016;311(3):H849–H854. https://doi.org/10.1152/ajpheart.00422.2016
Silva IVG, de Figueiredo RC, Rios, DRA. Effect of different classes of antihypertensive drugs on endothelial function and inflammation. International Journal of Molecular Sciences. 2019;20(14):3458.
McIlhenny S, Zhang P, Tulenko T, et al. eNOS transfection of adipose‐derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering. Journal of Tissue Engineering and Regenerative Medicine. 2015;9(11):1277-1285.