Yıl: 2010 Cilt: 10 Sayı: 1 Sayfa Aralığı: 18 - 27 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study

Öz:
Amaç: Miyokard infarktüsü (MI) sonrası gelişen ventriküler yeniden şekillenme (VR) ilerleyici sol ventrikül disfonksiyonunda önemli bir role sahiptir. Çalışmada sıçan iskemi-reperfüzyon modelinde MI sonrası nebivolol tedavisinin VR üzerine etkisini incelemeyi amaçladık. Yöntemler: Sıçanlar her grupta 12 hayvan olacak şekilde 3 gruba ayrıldı; operasyonel kontrol (sham-kontrol), MI kontrol (MI-kontrol) ve nebivolol uygulanmış MI (MI-nebivolol). Sol ventrikül (LV) çapları, hacimleri ve diyastolik dolum parametreleri ekokardiyografi ile incelendi. Yirmi sekiz günlük periyodun sonunda sistemik ve LV basınçları kaydedildi, plazma nitrik oksit (NO), peroksinitrit (ONOO-) düzeyleri ölçüldü, vücut (BW), kalp (HW) ve LV (LVW) ağırlıkları ile infarkt alanları belirlendi. Istatistiksel değerlendirme tekrarlı ölçümler varyans analizi ve ikili karşılaştırmalar Bonferroni testi ile yapıldı. Bulgular: İnfarktüs sonrası MI-kontrol grubunda belirgin VR parametreleri (LV çap ve hacminde artış, EF, FS ve arka duvar % kalınlık değişimde azalma) saptanırken (bütün karşılaştırmalar için p<0.05); bu değişiklikler MI-nebivolol grubunda MI-kontrol grubu ile karşılaştırıldığında kısıtlanmıştı (EF ve FS için sırası ile p=0.08 ve p=0.06). Sol ventrikül diyastol sonu basıncı (LVEDP) MI-nebivolol grubunda daha düşüktü (p<0.005). Yine bu grupta Δ±dp/dt değerleri daha yüksekti (p<0.05). İnfarktüs oluşturulmuş gruplarda infarkt alanları benzer olmasına rağmen (p=0.79); LVW/HW ve HW/BW değerleri MI-kontrol grubunda sham-kontrol grubuna göre daha yüksekti (bütün karşılaştırmalar için p<0.01). Bu değerler MI-nebivolol grubunda istatistiksel olarak anlamlı değildi.Plazma NO ve ONOO- düzeylerindeki artış da MI-nebivolol grubunda önlenmişti. Sonuç: Nebivolol tedavisi sıçanlarda MI sonrası gelişen VR'i azaltmıştır. Bu etki nebivololün kalp hızı ve kan basıncı düşürücü etkilerine bağlanamamıştır. Molekülün NO düzenleyici etkisi MI sonrası gelişen VR'de nebivololün yaralı etkilerinden sorumlu olabilir.
Anahtar Kelime:

Konular: Kalp ve Kalp Damar Sistemi

Nebivolol sıçan miyokardiyal infarktüs modelinde ventriküler yeniden şekillenmeyi önlüyor: Ekokardiyografik bir çalışma

Öz:
Ob­jec­ti­ve: Ventricular remodeling (VR) which develops after myocardial infarction (MI) plays an important role in progressive left ventricular dysfunction. We aimed to investigate the role of nebivolol treatment on VR after a MI in a rat ischemia-reperfusion model. Methods: Rats were divided into 3 groups of 12 each: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). Left ventricular (LV) diameters, volumes, and diastolic filling parameters were evaluated by echocardiography. On the 28th day, after recording the systemic and LV pressures and determining the plasma nitric oxide (NO) and peroxynitrite (ONOO-) levels , animals were sacrificed and heart, body and LV weights (HW, BW, LVW) were measured and infarct sizes were determined. Results were evaluated statistically by ANOVA for repeated measurements 3x3 factorial design with post-hoc Bonferroni test. Results: After MI, while VR (an increase in LV diameters and volumes associated with a decrease in EF, FS and posterior wall thickness change (LWPc) was significant in MI-control rats (p<0.05 for; all comparisons) these changes were significantly less in MI-nebivolol group (p=0.08 and p=0.06 for EF and FS respectively). LV end diastolic pres-sure (LVEDP) was lower (p<0.005) and &#916;±dp/dt&#8217;s (p<0.05) were higher in MI-nebivolol group compared to MI-control animals. Although infarct sizes were similar in MI-induced groups (p=0.79); LVW/HW and HW/BW&#8217;s were significantly greater in the MI-control group compared to sham-control (p<0.01 for all comparisons), these changes were not statistically significant in MI-nebivolol group. The increase in plasma NO and ONOO- levels were also prevented with nebivolol.Conclusion: Nebivolol therapy reduced the effects of VR in rats after MI. These beneficial effects were not related to its heart rate and blood pressure reducing effects. Nitric oxide regulatory action of this compound may contribute these beneficial effects on VR developed after MI.
Anahtar Kelime:

Konular: Kalp ve Kalp Damar Sistemi
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Antman EM, Braunwald E. Acute myocardial infarction. In: Braunwald E, Zipes D, Libby P, editors. Braunwald’s Heart Disease. 6th ed. Philadelphia: Elsevier Saunders Company; 2001.p. 1184-288.
  • 2. Volpi A, De Vita C, Franzosi MG, Geraci E, Maggioni AP, Mauri F, et al. Determinants of 6-month mortality in survivors of myocardial infarction after thrombolysis: Results of the GISSI-2 data base. The Ad hoc Working Group of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-2 Database. Circulation 1993; 88: 416-29. PMid:8339405
  • 3. Rumberger JA. Ventricular dilatation and remodeling after myocardial infarction. Mayo Clin Proc 1994; 69: 64-74.
  • 4. Dessy C, Saliez J, Ghisdal P, Daneau G, Lobysheva II, Frerart F, et al. Endothelial beta-3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary mi-crovessels in response to the third-generation beta-blocker nebivolol. Circulation 2005; 112: 1198-205. doi:10.1161/CIRCULATIONAHA.104.532960 PMid:16116070
  • 5. Chlopicki S, Kozlovski VI, Gryglewski RJ. NO-dependent vasodilatation induced by nebivolol in coronary circulation is not mediated by beta-adrenoreceptors or by 5HT1A receptors. J Phys Pharm 2002; 53: 615-24.
  • 6. Rahko PS. An echocardiographic analysis of the long-term effects of carvedilol on left ventricular remodeling, systolic performance, and ventricular filling patterns in dilated cardiomyopathy. Echocardiography 2005; 22: 547-54. doi:10.1111/j.1540-8175.2005.40057.x PMid:16060890
  • 7. Zanchetti A. Clinical pharmacodynamics of nebivolol: new evidence of nitric oxide-mediated vasodilating activity and peculiar haemodynamic properties in hypertensive patients. Blood Press 2005; 1: 17-32.
  • 8. Ignarro LJ. Experimental evidences of nitric oxide-dependent vasodilatory activity of nebivolol, a third-generation beta-blocker. Blood Press 2004; 1: 2-16. doi:10.1080/08038020410016557
  • 9. Edes I, Gasior Z, Wita K. Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: results of the ENECA study. Eur J Heart Fail 2005; 7: 631-9. doi:10.1016/j.ejheart.2004.10.015 PMid:15921805
  • 10. Wisenbaugh T, Katz I, Davis J, Essop R, Skoularigis J, Middlemost S, et al. Longterm (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. J Am Coll Cardiol 1993; 21: 1094-100. PMid:8096228
  • 11. Sacco G, Evangelista S, Criscuoli M, Gosco C, Bigioni M, Binaschi M, et al. Involvement of nitric oxide in both peripheral and central hemodynamic effect of D/L nebivolol and its enantiomers in rats. Eur J Pharmacol 2005; 511: 167-74. doi:10.1016/j.ejphar.2005.02.003 PMid:15792785
  • 12. Sánchez FV, Guerrero E, Ardanaz N. Effects of long term treatment with amlodipine or nebivolol in SHRs. 6th Internet World Congress for Biomedical Sciences, 2000.
  • 13. Palojoki E, Saraste A, Eriksson A, Pulkki K, Kallajoki M, Voipio-Pulkki LM, et al. Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol 2001; 280: 2726-31.
  • 14. St John Sutton M, Pfeffer MA, Plappert T, Rouleau JL, Moyé LA, Dagenais GR, et al. Quantitative twodimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction: the protective effects of captopril. Circulation 1994; 89: 68-75. PMid:8281697
  • 15. Gottdiener JS, Bednarz J, Devereux R, Gardin J, Klein A, Manning WJ, et al. American Society of Echocardiography Recommendations for Use of Echocardiography in Clinical Trials A Report from the American Society of Echocardiography’s Guidelines and Standards Committee and The Task Force on Echocardiography in Clinical Trials. J Am Soc Echocardiogr 2004; 17: 1086-119. doi:10.1016/S0894-7317(04)00675-3
  • 16. Doggrell SA, Brown L. Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 1998; 39: 89-105. doi:10.1016/S0008-6363(98)00076-5
  • 17.Feigenbaum H, Armstrong WF, Ryan T. Evaluation of systolic and diastolic function of the left ventricle. In Feigenbaum H, editors. Feigenbaum’s Echocardiography. Philadelphia: Lippincott Williams&Wilkins; 2005. p. 138-80.
  • 18. Wyatt HL, Mierbaum S, Heng MK, Gueret P, Corday E. Cross-sectional echocardiography: III Analysis of mathematical models for quantifying volume of symmetric and asymmetric left ventricle. Am Heart J 1980; 100: 8-21. doi:10.1016/0002-8703(80)90062-9
  • 19. Pfeffer JM, Pfeffer MA, Braunwald E. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res 1985; 57: 84-95. PMid:3891127
  • 20. Gaballa MA, Goldman S. Ventricular remodeling in heart failure.J. Cardiac Failure 2000; 6: 476-85.
  • 21. Beta-Blocker Pooling Project Research Group: The Beta-Blocker Pooling Project (BBPP) Subgroup findings from randomized trials in postinfarction patients. Eur Heart J 1988; 9: 8-16.
  • 22. Teerlink JR, Massie BM. Beta adrenergic blocker mortality trials in congestive heart failure. Am J Cardiol 1999; 84: 94-102. doi:10.1016/S0002-9149(99)00709-2
  • 23. Yang Y, Tang Y, Ruan Y, Zhang P, Zhou YW, Wang PH, et al. Comparative effects of carvedilol and losartan alone and in combination for preventing left ventricular remodeling after acute myocardial infarction in rats. Circ J 2003; 67: 159-62. doi:10.1253/circj.67.159 PMid:12548000
  • 24. Yang Y, Tang Y, Ruan Y, Wang Y, Gao R, Chen J, et al. Comparison of metoprolol with low, middle and high doses of carvedilol in prevention of postinfarction left ventricular remodeling in rats. Jpn Heart J 2003; 44: 979-87. doi:10.1536/jhj.44.979 PMid:14711192
  • 25. Fratta Pasini A, Garbin U, Nava MC, Stranieri C, Davoli A, Sawamura T, et al. Nebivolol decreases oxidative stress in essential hypertensive patients and increases nitric oxide by reducing its oxidative inactivation. J Hypertens 2005; 23: 589-96. doi:10.1097/01.hjh.0000160216.86597.ff
  • 26. Çelik T, İyisoy A, Kurşaklıoğlu H, Kardeşoğlu E, Kılıç S, Turhan H, et al. Compara-tive effects of nebivolol and metoprolol on oxidative stress, insulin resistance, plasma adiponectin and soluble P-selectin levels in hypertensive patients. J Hypertens 2006; 24: 591-6. doi:10.1097/01.hjh.0000209993.26057.de PMid:16467663
  • 27. Kurlianskaya AK, Atroshchenko ES, Pashuk OV. Improvement of endothelial function and intracardiac haemodynamic caused by nebivolol in patients with chronic heart failure. Eur J Heart Fail Suppl 2005; 4: 33. doi:10.1016/S1567-4215(05)80089-X
  • 28. ISIS-1 (First Intemational Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous atenolol among 16 027 cases of suspected acute myocardial infarction. Lancet 1986; 2: 57-66. PMid:2873379
  • 29. Litwin SE, Katz SE, Morgan JP, Douglas PS. Serial echocardiographic assessment of left ventricular geometry and function after large myocardial infarction in the rat. Circulation 1994; 89: 345-54. PMid:8281668
  • 30. Gupta S, Prahash ARC, Anand IS. Myocyte contractile function is intact in the postinfarct remodeled rat heart despite molecular alterations. Cardiovasc Res 2000; 48: 77-88. doi:10.1016/S0008-6363(00)00160-7
  • 31. Cantor EJ, Babick AP, Vasanji Z, Dhalla NS, Netticadan T. A comparative serial echocardiographic analysis of cardiac structure and function in rats subjected to pressure or volume overload. J. Mol Cell Card 2005; 38: 777-86. doi:10.1016/j.yjmcc.2005.02.012 PMid:15850571
  • 32. Lowes BD, Gill EA, Abraham WT, Larrain JR, Robertson AD, Bristow MR, et al. Effects of carvedilol on left ventricular mass, chamber geometry and mitral regurgitation in chronic heart failure. Am J Cardiol 1999; 83: 1201-5. doi:10.1016/S0002-9149(99)00059-4
  • 33. Yaoita H, Sakabe A, Maehara K, Maruyama Y. Different effects of carvedilol, metoprolol and propranolol on left ventricular remodeling after coronary stenosis or after permanent coronary occlusion in rats. Circulation 2002; 105: 975-80. doi:10.1161/hc0802.104503 PMid:11864928
  • 34. Omerovic E, Bollano E, Soussi B, Waagstein F. Selective b1-blockade attenuates postinfarct remodeling without improvement in myocardial energy metabolism and function in rats with heart failure. Eur J Heart Fail 2003; 5: 725-32. doi:10.1016/S1388-9842(03)00153-3
  • 35. Feuerstein G, Liu GL, Yue TL, Cheng HY, Hieble JP, Arch JR, et al. Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model. Eur J Pharmacol 1998; 351: 341-50. doi:10.1016/S0014-2999(98)00326-4
  • 36. Gilbert EM, Anderson JL, Deitchman D, Yanowitz FG, O'Connell JB, Renlund DG, et al. Long term betablocker vasodilator therapy improves cardiac function in idiopathic dilated cardiomyopathy: A double-blind randomized study of bucindolol versus placebo. Am J Med 1990; 88: 223-9. doi:10.1016/0002-9343(90)90146-5
  • 37. Brady AJB, Warren JB, Pool-Wilson PA, Williams TJ, Harding SE. Nitric oxide attenuates cardiac myocyte contraction. Am J Physiol 1993; 265: 176-82.
  • 38. Pinsky DJ, Cai B, Yang X, Rodriguez C, Sciacca RR, Cannon PJ. The lethal effects of cytokineinduced nitric oxide on cardiac myocytes are blocked by nitric oxide synthase antagonism of transforming growth factor β. J Clin Invest 1995; 95: 677-85. doi:10.1172/JCI117713 PMid:7532189 PMCid:295534
  • 39. Mebmer UK, Ankarcrona M, Nicotera P, Brune B. p53 expression in nitric oxide induced apoptosis. FEBS Lett 1994; 355: 23-6. doi:10.1016/0014-5793(94)01161-3
  • 40. Yasmin W, Strynadka K, Schulz R. Generation of peroxynitrite contributes to ischemiareperfusion injury in isolated rat hearts. Cardiovasc Res 1997; 332: 422-32. doi:10.1016/S0008-6363(96)00254-4
APA MERCANOĞLU H, PAMUKÇU B, SAFRAN N, MERCANOĞLU F, FICI F, GÜNGÖR M (2010). Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. , 18 - 27.
Chicago MERCANOĞLU HABİBE GÜLDEM,PAMUKÇU Burak,SAFRAN NURHAS,MERCANOĞLU Fehmi,FICI Francesco,GÜNGÖR Mehmet Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. (2010): 18 - 27.
MLA MERCANOĞLU HABİBE GÜLDEM,PAMUKÇU Burak,SAFRAN NURHAS,MERCANOĞLU Fehmi,FICI Francesco,GÜNGÖR Mehmet Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. , 2010, ss.18 - 27.
AMA MERCANOĞLU H,PAMUKÇU B,SAFRAN N,MERCANOĞLU F,FICI F,GÜNGÖR M Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. . 2010; 18 - 27.
Vancouver MERCANOĞLU H,PAMUKÇU B,SAFRAN N,MERCANOĞLU F,FICI F,GÜNGÖR M Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. . 2010; 18 - 27.
IEEE MERCANOĞLU H,PAMUKÇU B,SAFRAN N,MERCANOĞLU F,FICI F,GÜNGÖR M "Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study." , ss.18 - 27, 2010.
ISNAD MERCANOĞLU, HABİBE GÜLDEM vd. "Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study". (2010), 18-27.
APA MERCANOĞLU H, PAMUKÇU B, SAFRAN N, MERCANOĞLU F, FICI F, GÜNGÖR M (2010). Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. Anadolu Kardiyoloji Dergisi, 10(1), 18 - 27.
Chicago MERCANOĞLU HABİBE GÜLDEM,PAMUKÇU Burak,SAFRAN NURHAS,MERCANOĞLU Fehmi,FICI Francesco,GÜNGÖR Mehmet Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. Anadolu Kardiyoloji Dergisi 10, no.1 (2010): 18 - 27.
MLA MERCANOĞLU HABİBE GÜLDEM,PAMUKÇU Burak,SAFRAN NURHAS,MERCANOĞLU Fehmi,FICI Francesco,GÜNGÖR Mehmet Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. Anadolu Kardiyoloji Dergisi, vol.10, no.1, 2010, ss.18 - 27.
AMA MERCANOĞLU H,PAMUKÇU B,SAFRAN N,MERCANOĞLU F,FICI F,GÜNGÖR M Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. Anadolu Kardiyoloji Dergisi. 2010; 10(1): 18 - 27.
Vancouver MERCANOĞLU H,PAMUKÇU B,SAFRAN N,MERCANOĞLU F,FICI F,GÜNGÖR M Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study. Anadolu Kardiyoloji Dergisi. 2010; 10(1): 18 - 27.
IEEE MERCANOĞLU H,PAMUKÇU B,SAFRAN N,MERCANOĞLU F,FICI F,GÜNGÖR M "Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study." Anadolu Kardiyoloji Dergisi, 10, ss.18 - 27, 2010.
ISNAD MERCANOĞLU, HABİBE GÜLDEM vd. "Nebivolol prevents remodeling in a rat myocardial infarction model: An echocardiographic study". Anadolu Kardiyoloji Dergisi 10/1 (2010), 18-27.