Alcohol-induced changes in the serum of vascular endothelial growth factor and electrical inhomogeneity of the myocardium in young patients

The aim was to study alcohol-induced changes in the electrical inhomogeneity of the myocardium and the level of vascular endothelial growth factor in blood serum in young patients. 92 patients were examined. The first group consisted of 30 men and 30 women in a state of acute intoxication with subsequent examination of the withdrawal state in the clinic, the second group included 16 men and 16 women in a withdrawal state upon admission to the clinic. Age of patients in the first group: 36,00 (33,75-40,00) years (women) and 37,50 (33,75-41,25) years – men, age of patients of the second group: 36,00 (35,00-39,75) years (women) and 37,50 (34,25-39,75) years (men). The control group consisted of healthy individuals: 15 men aged 35,00 (29,00-39,00) years and 15 women aged 31,00 (28,00-40,00) years. The dispersion of the QTd interval was assessed using a high-resolution electrocardiography apparatus Poly-Spectrum 8/EX (Russia), in 12 standard leads, lasting 10 seconds. The concentration of ethanol in the blood was determined by an Agilent 6850 chromatograph (USA). Serum concentration of vascular endothelial growth factor was assessed using the Vector-Best reagent kit (Russia) on an enzyme immunoassay analyzer Hospitex diagnostics Plate Screen (Italy). Evaluation of the serum concentration of vascular endothelial growth factor in young alcohol-dependent patients showed an increase in its content, both in the acute and withdrawal periods, compared with patients in the control group. At the same time, there was a trend towards higher vascular endothelial growth factor values in men compared to women. It was found that the prehospital course of the withdrawal period is characterized by higher concentrations of serum vascular endothelial growth factor, compared with patients in whom the withdrawal period began in the clinic after acute alcohol intoxication. The hospital withdrawal period was accompanied by an increase in the value of the corrected dispersion of QTcd among women and men, compared with the acute period. Analysis of the incidence of violations of the processes of repolarization of the ventricular myocardium in the withdrawal period revealed its predominance in women compared to men. The development of a strategy for early prenosological diagnosis of myocardial arrhythmogenic activity, including the assessment of electrical inhomogeneity, made it possible to reveal the prevalence among young women of a more frequent occurrence of arrhythmogenic myocardial vulnerability in the withdrawal period of alcoholic excess compared to men. Alcohol-induced electrical inhomogeneity of the myocardium is accompanied by an increase in the serum concentration of vascular endothelial growth factor in young patients without overt cardiac pathology.

1. Bokeriya L. A., Bokeriya O. L., Le T. G. Electrophysiological remodeling of myocardium in heart failure and various heart disease // Annaly aritmologii. 2010. 7 (4) 41-48. (In Russ.)

2. Semernin E. N., Gudkova A. Ya. Alcoholic heart disease. Clinical and genetic and morpho-functional aspects. Modern presentation // Arterial hypertension. 2008; 14 (1-S2): 96-103. (In Russ.)

3. Gurevich M. A. The problem of non-criminal diseases of myocardium in clinical practice // Russian medical journal. 1998; 6 (24): 56-64. (In Russ.)

4. Ronksley P. E., Brien S. E., Turner B. J., Mukamal K. J., Ghali W. A. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis // BMJ. 2011; 342: d671. DOI: 10.1136/bmj.d671.

5. Jayasekara H., English D. R., Room R., MacInnis R. J. Alcohol consumption over time and risk of death: a systematic review and meta-analysis // American Journal of Epidemiology. 2014; 179 (9): 1049-1059. DOI: 10.1093/aje/kwu028.

6. Anderson P., Baumberg B. Alcohol in Europe – Public Health Perspective: Report summary, Drugs: Education, Prevention and Policy. 2006; 6 (13): 483-488. DOI: 10.1080/09687630600902477.

7. Koshkina E. A., Kirzhanova V. V., Guseva O. I., Grigorova N. I., Mugantseva L. A. Provision of drug treatment to the population of the Russian Federation in 2012 // Voprosy narkologii. 2013; 4: 3-18. (In Russ.)

8. Anan Huang, Xin Qi, Yameng Cui, Yulin Wu, Shiqi Zhou, Mingyin Zhang. Serum VEGF: Diagnostic Value of Acute Coronary Syndrome from Stable Angina Pectoris and Prognostic Value of Coronary Artery Disease // Cardiology Research and Practice 2020, vol. 2020, Article ID 6786302, 8 pages. DOI: 10.1155/2020/6786302.

9. Hojo Y., Ikeda U., Okada M. et al. Expression of vascular endothelial growth factor in patients with acute myocardial infarction // J. Amer. Coll. Cardiol. 2000; (35): 968-973. DOI: 10.1016/S0735-1097(99)00632-4.

10. Trapé J., Morales C., Molina R., Filella X., Marcos J. M., Salinas R., Franquesa J. Vascular endothelial growth factor serum concentrations in hypercholesterolemic patients // Scand J Clin Lab Invest. 2006; 66 (3): 261-267. DOI: 10.1080/00365510600564949.

11. Shibuya M. Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases // Journal of Biochemistry. 2013; 153 (1): 13-19. DOI: 10.1093/jb/mvs136.

12. Sergienko I. V. Factors of coronary angiogenesis and the influence of various methods of treatment in patients with coronary heart disease: avtoreferat dis. ... doktora meditsinskikh nauk: 14.01.05. Moskva, 2009. 37 s. (In Russ.)

13. Ramos C., Napoleão P., Selas M., Freixo C., Viegas Crespo A. M., Mota Carmo M., Cruz Ferreira R., Pinheiro T. Prognostic value of VEGF in patients submitted to percutaneous coronary intervention // Dis Markers. 2014; 2014: 135357. DOI: 10.1155/2014/135357.

14. Kucukardali Y., Aydogdu S., Ozmen N., Yonem A., Solmazgul E., Ozyurt M., Cingozbay Y., Aydogdu A. The relationship between severity of coronary artery disease and plasma level of vascular endothelial growth factor // Cardiovasc Revasc Med. 2008; 9 (2): 66-70. DOI: 10.1016/j.carrev.2007.11.005.

15. Makin A. J., Chung N. A., Silverman S. H., Lip G. Y. Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: alink between angiogenesis and thrombogenesis? // Clin. Sci. (Lond.). 2003; 104 (4): 397-404. DOI: 10.1042/CS20020182.

16. Zangelova T. E., Gladkikh N. N., Yagoda A. V. Prognostic significance of the vascular endothelial growth factor in patients with a mitral valve prolapse during connective tissue dysplasia // Meditsinskiy vestnik Severnogo Kavkaza. 2017; 4 (12): 361-365. (In Russ.)

17. Kaza E., Ablasser K., Poutias D., Griffiths E. R., Saad F. A., Hofstaetter J. G., del Nido P. J., Friehs I. Up-regulation of soluble vascular endothelial growth factor receptor-1 prevents angiogenesis in hypertrophied myocardium // Cardiovasc Res. 2011; 89 (2): 410-418. DOI: 10.1093/cvr/cvq321.

18. Zhao T., Zhao W., Meng W., Liu C., Chen Y., Gerling I. C., Weber K. T., Bhattacharya S. K., Kumar R., Sun Y. VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium // Am J Transl Res. 2015; 7 (4): 697-709.

19. Han X., Liu L., Niu J., Yang J., Zhang Z., Zhang Z. Serum VEGF Predicts Worse Clinical Outcome of Patients with Coronary Heart Disease After Percutaneous Coronary Intervention Therapy // Med Sci Monit. 2015; 21: 3247-3251. DOI: 10.12659/msm.894803.

20. Maurea N., Coppola C., Piscopo G., Galletta F., Riccio G., Esposito E., De Lorenzo C., De Laurentiis M., Spallarossa P., Mercuro G. Pathophysiology of cardiotoxicity from target therapy and angiogenesis inhibitors // J Cardiovasc Med (Hagerstown). 2016 May; 17 Suppl 1, Special issue on Cardiotoxicity from Antiblastic Drugs and Cardioprotection: e19-e26. DOI: 10.2459/JCM.0000000000000377.

21. Vtorushina Yu. S. The state of intoxication in the system of norms of the common and special parts of the Criminal Code of the Russian Federation // Sibirskiy yuridicheskiy vestnik. 2018; 2: 71-75. (In Russ.)

22. Lin Z., Xing W., Gao C., Wang X., Qi D., Dai G., Zhao W., Yan G. Inhibitory Effect of Vascular Endothelial Growth Factor on the Slowly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes // J Am Heart Assoc. 2018; 7 (3): e007730. DOI: 10.1161/JAHA.117.007730.

23. Lu Z., Wu C. Y., Jiang Y. P., Ballou L. M., Clausen C., Cohen I. S., Lin R. Z. Suppression of phosphoinositide 3-kinase signaling and alteration of multiple ion currents in drug-induced long QT syndrome // Sci Transl Med. 2012; 4 (131): 131ra50. DOI: 10.1126/scitranslmed.3003623.

24. Ballou L. M., Lin R. Z., Cohen I. S. Control of cardiac repolarization by phosphoinositide 3-kinase signaling to ion channels // Circ Res. 2015; 116 (1): 127-137. DOI: 10.1161/CIRCRESAHA.116.303975.

25. Won Y. W., McGinn A. N., Lee M., Nam K., Bull D. A., Kim S. W. Posttranslational regulation of a hypoxia-responsive VEGF plasmid for the treatment of myocardial ischemia // Biomaterials. 2013; 34 (26): 6229-6238. DOI: 10.1016/j.biomaterials.2013.04.061.

26. Matsumoto R., Omura T., Yoshiyama M., Hayashi T., Inamoto S., Koh K. R., Ohta K., Izumi Y., Nakamura Y., Akioka K., Kitaura Y., Takeuchi K., Yoshikawa J. Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction // Arterioscler Thromb Vasc Biol. 2005; 25: 1168-1173.

27. Xing W., Gao C., Qi D., Zhang Y., Hao P., Dai G., Yan G. Enhanced effect of VEGF165 on L-type calcium currents in guinea-pig cardiac ventricular myocytes // Biomed Pharmacother. 2017; 85: 697-703. DOI: 10.1016/j.biopha.2016.11.082.

28. Belogubov P. V., Ruzov V. I., Butov A. A., Burmistrova V. G., Sharafutdinova R. R., Belogubova K. N. Gender-specific features of alcohol-induced electrical heterogeneity of myocardium in young patients // Bulletin of SurGU. Medicine: scientific and practical journal. 2020; 3 (45): 31-37. (In Russ.)