Ali Gökhan ÖZYILDIZ, Afag ÖZYILDIZ, Mustafa ÇETİN

SPESİFİK OLMAYAN OKSİDATIF BİR BELİRTEÇ OLAN GAMA-GLUTAMİL TRANSFERAZ SEVİYESİ HİS-VENTRİKÜLER ARALIĞI UZAMASI İLE BAĞIMSIZ İLİŞKİLİDİR

Giriş: His-ventrikül (H-V) aralığı, His-Purkinje sistemi iletim süresini yansıtır ve elektrofizyolojik çalışmanın (EPS) temel ölçümlerinden biridir. H-V süresi uzamasında fibrozis ve yağ infiltrasyonu rol oynar. Son çalışmalar, iletim sistemindeki fibrozisin oksidatif stres tarafından tetiklenebileceğini iddia etmektedir. Gama-glutamil transferaz (GGT), oksidatif stresin spesifik olmayan bir belirtecidir ve klinikte pratik olarak değerlendirilebilir. Çalışma, H-V interval uzaması ile GGT düzeyi arasındaki ilişkiyi araştırmayı amaçlamıştır. Yöntemler: Çalışmaya supraventriküler taşikardi tanısı ile klinik olarak endike EPS uygulanan ardışık 94 hasta (58 kadın) dahil edildi. İşlem öncesi rutin laboratuvar tetkikleri ve gama-glutamil transferaz düzeyi ölçüldü. Hastalara standart EPS protokolü uygulanarak Atriyal- His, H-V süreleri ve bazal siklus uzunluğu ölçüldü. Bulgular: Hastaların yaş ortalaması 47.9±15.8 yıl idi. Katılımcılar H-V süresine göre ≤ 55 ms (n=66) ve >55 ms (n=28) olmak üzere iki grupta analiz edildi. Çok değişkenli lojistik regresyon analizinde vücut kitle indeksi (VKİ) (OR 1,153, %95 CI 1,029-1,292, p=0,014) ve GGT seviyeleri (OR 1,060, %95 CI 1,013-1,108, p=0,012) H-V süresi uzaması ile bağımsız ilişkiliydi. Sonuç: Gama-glutamil transferaz düzeyi ve VKİ H-V süresi uzamasıyla bağımsız olarak ilişkilidir. Kapsamlı çalışmalarla doğrulanması gereken GGT ve H-V süresi ilişkisi, infra-His iletim kusuru olan hastaların takibinde pratik bir yardımcı olabilir.

Anahtar Kelimeler:

Gama-glutamil transferaz, His-ventrikül süresi, Oksidatif stres

LEVEL OF GAMMA-GLUTAMYL TRANSFERASE - A NONSPECIFIC OXIDATIVE MARKER - IS INDEPENDENTLY ASSOCIATED WITH HIS-VENTRICULAR INTERVAL PROLONGATION

Introduction: His-ventricle (H-V) interval is one of the basic measurements of the electrophysiology study (EPS), reflecting conduction time through the His-Purkinje system. Fibrosis and fatty infiltration take a role in the development of H-V interval prolongation. Recent studies claimed that fibrosis in the conduction system could be triggered by oxidative stress. Gamma-glutamyl transferase (GGT) is a non-specific marker of oxidative stress and can be practically evaluated in the clinic. The study aimed to investigate the association of H-V interval prolongation and GGT level. Methods: The study included 94 consecutive patients (58 women) who underwent clinically indicated EPS with the diagnosis of supraventricular tachycardia. Gamma-glutamyl transferase level was measured with routine laboratory tests before the procedure. Atrial-His, H-V intervals and basal cycle length were measured by performing the standard EPS protocol to patients. Results: Patient’s mean age was 47.9±15.8 years. Participants were analyzed in two groups according to the duration of the H-V interval: ≤ 55 ms (n=66) and >55 ms (n=28). Body-mass index (BMI) (OR 1.153, 95% CI 1.029-1.292, p=0.014) and GGT levels (OR 1.060, 95% CI 1.013-1.108, p=0.012) were independently associated with H-V interval prolongation in multivariate logistic regression analysis. Conclusion: Gamma-glutamyl transferase and BMI are independently associated with H-V interval prolongation. The relationship of GGT with H-V interval, which extensive studies should confirm, can be a practical aid in the follow-up of patients with infra-His conduction defects.

Keywords:

Gamma-glutamyl transferase, His-Ventricle interval, Oxidative stress,

PDF

___

1- Miller JM, Zipes DP. Diagnosis of Cardiac Arrhythmias, in: Braunwald’s Heart Disease, Mann DL, et al, 10th edition. Elsevier Saunders, Philadelphia. 2015:670-1.
2- Tadic M, Cuspidi C. The influence of type 2 diabetes on left atrial remodeling. Clin Cardiol. 2015;38(1):48-55. Doi: 10.1002/clc.22334.
3- Sovari AA. Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress. Cardiol Res Pract. 2016;2016:9656078. Doi: 10.1155/2016/9656078.
4- Karam BS, Chavez-Moreno A, Koh W, Akar JG, Akar FG. Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes. Cardiovasc Diabetol. 2017;16(1):120. Doi: 10.1186/s12933-017-0604-9.
5- Sesso HD, Buring JE, Chriten EG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. Jama. 2008;300(18):2123-33. Doi: 10.1001/jama.2008.600.
6- Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263-355. Doi: 10.1080/20014091084227.
7- Forman HJ, Liu RM, Tian L. Glutathione cycling in oxidative stress, in: Lung Biology in Health and Disease. Vol. 105. Oxygen, gene expression, and cellular function. Biadasz L, Clerch L, Massaro DJ. Marcel Dekker, New York. 1997:99-121.
8- Lee DH, Blomhoff R, Jacobs Jr DR. Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radic Res. 2004;38(6):535-9. Doi: 10.1080/10715760410001694026.
9- El Hadi H, Vettor R, Rossato M. Cardiomyocyte mitochondrial dysfunction in diabetes and its contribution in cardiac arrhythmogenesis. Mitochondrion. 2019;46:6-14. Doi: 10.1016/j.mito.2019.03.005.
10- Tse G, Yan BP, Chan YWF, Tian XY, Huang Y. Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis. Front Physiol. 2016;7:313. Doi: 10.3389/fphys.2016.00313.
11- de Bakker JM, van Capelle FJ, Janse MJ, Wilde AA, Coronel R, Becker AE, et al. Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation. Circulation. 1988;77(3):589-606. Doi: 10.1161/01.cir.77.3.589.
12- Morita N, Sovari AA, Xie Y, Fishbein MC, Mandel WJ, Garfinkel A, et al. Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress. Am J Physiol Heart Circ Physiol. 2009;297(5):1594-605. Doi: 10.1152/ajpheart.00579.2009.
13- van Wagoner DR. Oxidative stress and inflammation in atrial fibrillation: role in pathogenesis and potential as a therapeutic target. J Cardiovasc Pharmacol. 2008;52(4):306-13. Doi: 10.1097/FJC.0b013e31817f9398.
14- Shimano M, Shibata R, Inden Y, Yoshida N, Uchikawa T, Tsuji Y. Reactive oxidative metabolites are associated with atrial conduction disturbance in patients with atrial fibrillation. Heart Rhythm. 2009;6(7):935-40. Doi: 10.1016/j.hrthm.2009.03.012.
15- Oliveira BF, Nogueira-Machado JA, Chaves MM. The Role of Oxidative Stress in the Aging Process. Scientific World Journal. 2010;10:1121-8. Doi: 10.1100/tsw.2010.94.
16- Chaturvedi A, Natarajan A, Sharma V, Bambrana V, Yaparthy N, Shetty JK, et al. Association of age-related severity in oxidative stress and blood urea nitrogen levels in patients with dementia: A coastal Karnataka study. Asian j biomed pharm sci. 2015;5(44):6-10. Doi: 10.15272/ajbps.v5i44.688.
17- Lee DH, Jacobs Jr DR, Gross M, Kiefe CI, Roseman J, Lewis CE, et al. Gamma-glutamyltransferase is a predictor of incident diabetes and hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Clin Chem. 2003;49(8):1358-66. Doi: 10.1373/49.8.1358.
18- Maellaro E, Dominici S, Del Bello B, Valentini MA, Pieri L, Perego P. Membrane gamma-glutamyl transpeptidase activity of melanoma cells: effects on cellular H(2)O(2) production, cell surface protein thiol oxidation and NF-kappa B activation status. J Cell Sci. 2000;113(15):2671-8. PMID: 10893182
19- DeBari MK, Abbott RD. Adipose Tissue Fibrosis: Mechanisms, Models, and Importance. Int J Mol Sci. 2020;21(17):6030. Doi: 10.3390/ijms21176030.
20- Venteclef N, Guglielmi V, Balse E, Gaborit B, Cotillard A, Atassi F, et al. Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur Heart J. 2015;36(13);795-805. Doi: 10.1093/eurheartj/eht099.
21- Magnani JW, Lopez FL, Soliman EZ, Maclehose RF, Crow RS, Alonso A. P Wave Indices, Obesity, and the Metabolic Syndrome: The Atherosclerosis Risk in Communities Study. Obesity. 2012;20(3):666-72. Doi: 10.1038/oby.2011.53.
22- Pathak RK, Mahajan R, Lau DH, Sanders P. The Implications of Obesity for Cardiac Arrhythmia Mechanisms and Management. Can J Cardiol. 2015;31(2):203-10. Doi: 10.1016/j.cjca.2014.10.027.
23- Mayne ST. Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. J Nutr. 2003;133(3);933-40. Doi: 10.1093/jn/133.3.933S.