Sezgin ALBAYRAK, Kemal KARAAĞAÇ, Zeynel Abidin YETGİN, İbrahim BARAN, Ali AYDINLAR, Hakan UÇAR

Carvedilol and metoprolol in acute myocardial infarction early effect of oxidized LDL and paraoxonase -1 activity

Amaç: Bu çalışmanın amacı akut miyokard infarktüsü (AMİ)geçiren hastalarda dört haftalık karvedilol ve metoprololtedavisinin okside düşük yoğunluklu lipoprotein (LDL) düzeyive paraoksanaz -1 (PON -1) aktivitesi üzerine etkisini araştı rmaktır. Yöntem: Çalışmaya AMİ tanısı konulan 31 hasta ve kontrolgrubunu oluşturacak 15 olgu alındı. AMİ grubundan 15 ha staya karvedilol ve 16 hastaya metoprolol tedavisi verilerekçalışma iki guruba randomize edildi. Çalışmanın sonundabaşvuru ve kontrol vizitinde alınan ve saklanan kan örnekl erinden okside LDLnin ve PON -1 aktivitesinin başvuru (tedaviöncesi) ve tedavi sonrası 1 aylık sonuçlarına bakıldı. Bulgular : Hasta grubunda kontrol grubuna kıyasla başlangıçHDL düzeyi ve PON -1 aktivitesi anl amlı derecede düşükolarak saptandı. Okside LDL düzeyi hasta grubunda kontrolgrubuna göre daha yüksekti. Hasta grubunda 1 aylık karved iol (p=0,008) ve metoprolol (p Sonuç : AMİ geçiren hastalarda diğer çalışmalara paralelolarak, okside LDL' nin arttığı ve HDL -K düzeyi ile PON-1aktivitesinin azaldığı gösterildi. Antioksidan özellikleri ned eniyle Karvedilolün PON -1 aktivitesini arttırmada Metopr oole göre daha üstün olması beklenebilir. Fakat bir aylık sürebunu göstermek için yeterli olmayabilir.

Akut miyokard infarktüsünde karvedilol ve metoprolol ün okside LDL ve paraoksonaz-1 aktivitesine erken dönem etkisi

Objective : The aim of this study to investigate the effects ofCarvedilol and Metoprolol on oxidized low density lipoprotein (oxLDL) and paraoxonase -1 (PON -1) activity in patientswith acute myocardial infarction who were treated w iththese agents for four weeks.Method : 31 patients with AMI and 15 healhty subjects forcontrol group were contained. 15 patients of AMI groupwere given Carvedilol treatment and the remained 16 weregiven Metoprolol treatment and the study was randomizedto two groups. At the en d of the study oxLDL and PON -1activity levels were studied from the blood samples taken atadmission (pre treatment) and samples taken after onemonth treatment. Results : In patient group initial high density lipoprotein(HDL) level and PON -1 activity were found significantly lowerbut oxLDL level was higher in patient group compared tocontrol group. The oxLDL levels were found to decrease inpatient group after Carvedilol(p=0,008) and Metoprolol (pConclusion : In paralel to other studies we showed thatoxLDL is increased and HDL and PON -1 activity is decreasedin patients with AMI. Carvedilol may be expected to besuperior to Metoprolol due to its antioxidant effect in increasing PON-1 acitvity. But one month period may not beenough to determine this effect.

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1. Ross R. The pathogenesis of atherosclerosis: A perspe ctive for the 1990s. Nature 1993; 362(6423):801 -9
2. Carmena R, Ascaso JF, Camejo G, Varela G, Hurt-Camejo E, Ordovas JM, et al. Effect of olive and sunflower oils on low density lipoprotein level, composition, size, oxidation and interaction with arterial proteoglycans. Atheroscler osis. 1996;125(2):243 -55.
3. Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS, et al. Oxidized phospholipids, Lp(a) lip oprotein, and coronary artery disease. N Engl J Med 2005; 353(1):46 -57
4. Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoperoxides in low -density lipoprotein. FEBS Lett 1991;286(1 -2): 152 4.
5. Mackness MI, Mackness B, Durrington PN, Connelly PW, HegeleRA. Paraoxonase: biochemistry, genetics and rel ationship to plasmalipoproteins. Curr Opin Lipidol 1996;7(2): 6976.
6. Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, et al. Human serum paraoxonase is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med 1999;26(7 -8): 892 904.
7. Eckerson HW, Wyte CM, La Du BN. The human serum paraoxonase/ arylesterase polymorphi sm. Am J Hum Genet 1983; 35(6): 1126-38.
8.Yusuf S, Sleight P, Rosi PRF, Ramsdale D, Peto R, Furze L, et al. Reduction in infarct size, arrhythmias, chest pain, and morbidity by early intravenous beta-blockade in suspected acute myocardial infarction. Circulation 1983; 67 (6 Pt 2): I32 -41.
9. Feuerstein GZ, Hamburger SA, Smith EF, Bril A, Ruffolo RR, Myocardial protection with Carvedilol. J Cardiovasc Pharmacol 1992; 19:S138 -41.
10. McElveen J, Mackness MI, Colley CM, Peard T, Warner S, Walker CH. Distribution of paraoxon hydrolytic activity in the serum of patients after myocardial infarction. Clin Chem1986; 32(4): 671 -3.
11. Ombres D, Pannitteri G, Montali A, Candeloro A, Seccareccia F, Campagna F, et al. The Gln -Argl92 polymo rphism of human paraoxonase gene ıs not associated with coronary artery disease in Italian patients. Arterioscler Thromb Vasc Biol 1998;18(10):1611 -6.
12.Aviram M, Hardak E, Vaya J, Mahmood S, Milo S, Hoffman A, et al. Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human cor onary and carotid atherosclerotic lesions. Circulation 2000; 101(21): 2510 -7.
13.Aviram M, Rosenblat M, Bisgair CL, Newton RS, Primo - Parmo SL, La Du BN Paraoxonase inhibits high density lipoprotein (HDL) oxidation and preserves its functions: a possible peroxidative role for paraoxonase. J Clin Invest 1998; 101(8): 1581 -90.
14. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, et al. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lip oprotein. J Clin Invest 1995;96(6):288291.
15. Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, et al. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 2001;103(15):195560.
16. Holvet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D. Oxidized LDL and Malondialdehyde -Modified LDL in Patients With Acute Coronary Syndromes and Stable Coronary Artery Disease. Circulation 1998;9(15)8:1487-1494.
17. Halliwell B, Gutteridge JM, Cross CE, Free rad icals,antioxidants, and human disease: where are we now? J Lab Clin Med 1992:119(6):598-620.
18.Devasagayam TP, Tilac JC, Boloor KK Sane KS, Ghaskadbi SS, Lele RD. Free radicals and antioxidants in human health: curent status and future prospects. J Assoc Phisicians India 2004;52: 794 -804.
19. Serdar Z, Serdar Z, Altın A, Albayrak S. et al. The rel ation between oxidant and antioxidant parameters and severity of acute coronary syndromes. Acta Cardiol 2007; 62(4):373 -80.
20. Jialal I, Vega G, Grundy S. Physiological levels of asco rbate inhibit the oxidative modification of LDL. Atheroscl erosis 1990;82(3):185 91.
21. Aviram M, Rosenblat M, Bisgair CL, Newton RS, Primo - Parmo SL, La Du BN Paraoxonase inhibits high density lipoprotein (HDL) oxidation and preserves its functions: a possible peroxidative role for paraoxonase. J Clin Invest 1998; 101(8): 1581 -90.
22. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart di sease and lipoprotein cholesterol levels. The Framingham Study. J Am Med Assoc 1986;256(20):2835 8.