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International Journal of Medicine Research
ISSN: 2455-7404; Impact Factor: RJIF 5.42
www.medicinesjournal.com
Volume 1; Issue 2; May 2016; Page No. 148-151

Effects of bisoprolol and nebivolol on the spectrum of essential amino acids in the blood serum of
patients with unstable angina
1 Zavalskaya TV, 2 Dr. Lizogub VG
1 Department of General Medicine №4, Bogomolets National Medical University, Ukraine 2 Professor, Head of the Department, Bogomolets National Medical University, Ukraine
Abstract
The study involved patients with unstable angina. Ion exchange liquid-column chromatography method was used. Levels of non-
essential amino acids was determined in the blood plasma. In patients with unstable angina, antianginal therapy which include
Nebivolol, compared with patients taking bisoprolol, serum normalized level of ornithine, taurine, tyrosine. In both groups returned
to normal levels of glutamine.
Keywords: Unstable angina, amino acid, antianginal therapy, bisoprolol, nebivolol.
1. Introduction
The ability to influence on lipid metabolism, increase blood One of the most important mediators that are functionally glucose and blood lipid levels gave reasons to the involved in different biological processes, is nitric oxide (NO). Recommendations of the European Society of Cardiology in NO indirectly causes relaxation of the muscular layer. One of 2007 to limit the use of beta-blockers, especially in combination the most important and most studied target organ for NO is the with thiazide diuretics in patients with diabetes mellitus and cardiovascular system, where it becomes one of the regulatory metabolic syndrome. However, the recommendations of 2013, factors, carrying out in particular cardio protective functions, presented at the congress of the European Society of Cardiology enhances the body's needs in the local perfusion in ischemic for hypertension in June 2013 made amendments on β blockers, conditions (Bulanova E.L. et al, 2014; Ivashkin V.T. et al, 2001) which have vasodilating properties. Among such drugs are called [1, 3]. NO is synthesized in the coronary endothelium, celiprolol, nebivolol, carvedilol and (Mancia G. et al., 2013) [11]. endocardium, cardiomyocytes. Increased levels of NO in Advantage of using nebivolol is proved as compared with other intracellular concentration of cGMP, increases ventricular beta-blockers, in particular bisoprololum, IHD patients in their diastolic relaxation and tension, improving the contractile effect on platelet aggregation (Chen S. et al., 2015) [13]. function of the myocardium. Under experimental conditions, it Due to above described properties of nebivolol, it's useful to was found that NO has a marked influence on the heart and analyze / study its effects on the spectrum of essential amino hemodynamics, causing a decrease in heart rate, stroke volume, acids in the blood serum of patients with unstable angina, in increased PQ interval duration and blood expulsion period. comparison with other β adrenoceptor - bisoprololum. Probably, NO, resulting in cardiomyocytes provides b- adrenergic negative inotropic and chronotropic action (Nasyrova Purpose of the study
A.G., 2004; Brutsaert D.L., 2003) [9, 12]. As NO is synthesized in Compare the effectiveness of antianginal therapy, which includes the vascular endothelium, it is involved in the regulation of the bisoprolol with antianginal therapy, which consists of nebivolol tone as an antagonist of the adrenergic nervous system. in the treatment of essential amino acids balance disorders in the Given these effects of NO, drugs of interest, which are its blood serum of patients with unstable angina (UA). donators or potentiate its release by the endothelium. Drug of
Material and Methods
choice, in particular, β-blockers (BAB), nebivolol (nebilet, The study involved 68 unstable angina (UA) patients aged 65 to binelol) Nebivolol (Nebilet, Berlin-Chemie) - a highly selective 76 years (average age of patients was 68,2 ± 6,3 years). The blocker of β 1-adrenergic receptors 3rd generation. A feature of patients were divided into two groups: 35 people treated this product is its ability to stimulate the synthesis of NO by the kardiket, bisoprolol, Atoris, Enap, aspirin, clopidogrel, and 38 endothelium due to the effect of beta-adrenergic receptors are 3 people, which include Nebivolol therapy. All study group types. Probably, their stimulation causes the release of NO by patients were statistically homogeneous and comparable. (UA) the endothelium. In atrial tissue this receptor subtype is involved diagnosis was made on the basis of the order/protocol of the in the regulation of ion channels. The functions of these Ministry of Health of Ukraine dated 03.07.2006, № 436 "On receptors in adipose tissue lipolysis and include regulation of Approval of the provision of medical care protocols, specialty" carbohydrate metabolism (Moshkovska Yu. O., 2015) [8]. Cardiology ". The survey did not include patients with heart Since 2005, nebivolol is included in the European guidelines for failure IIB and stage III, atrial fibrillation, concomitant diseases the treatment of cardiac insufficiency, regardless of gender, age in the stage of decompensation, cancer, diseases of the and ejection fraction of the left ventricle (Kovalenko V.M. et al., musculoskeletal system. For the objective investigation of amino acid, blood serum was potassium ions, which contribute to increase in strength of used. We used the method of ion-exchange liquid- muscle contraction and the muscle force of contraction of the chromatography column. In the blood plasma, the following was myocardium in particular. determined: non-essential amino acid (AA): ornithine, taurine, Patients on both treatment groups after treatment significantly aspartic acid, serine, glutamic acid, proline, glycine, alanine, decreased proline serum respectively 4.74 mg / mol / 100 ml (p cysteine, tyrosine, glutamine. <0.05) and 3.39 mg / mole / 100ml (p <0.05) but remained The research results were processed on the PC using Microsoft significantly lower compared to the CG, respectively, at 8.5 mg Office software package. Statistical analysis of the data used, / mole / 100ml (p <0.05) and 19.85 mg / mol / 100 ml (p <0.05). Microsoft Excel 2010. The significance of differences between Interesting was dynamics of change of glycine in blood serum the average performance of different groups was detected by in patients with UA. Patients taking bisoprolol, level of AA had using Student's t-test or Pearson criteria. increased significantly as compared with before treatment and 4.28 kg, respectively, mg / mol / 100 ml and 5.29 mg / mole / Results and discussion
100ml (both p <0.05), and in patients whose therapy included Comparing the results of treatment in patients treated with nebivolol, glycine levels significantly decreased as compared various beta-blockers, it can be concluded that no significant with before treatment and 11.2 kg, respectively mg / mol / 100 difference in the dynamics of the total amount of non-essential ml and 10.9 mg / mole / 100ml (both p <0.05). (AA) serum as compared with before treatment, and with the Since myocardial ischemia reduces oxygen level, which leads to index control group(CG) have been identified (all < 0.05). an increase in the generated cytotoxic superoxide anion radicals It should be noted that the intake of nebivolol in patients with and other forms of reactive oxygen, there is a sharp irreversible UA compared to the CG had normalized ornithine levels in inhibition of the antioxidant enzymes superoxide dismutase and serum (P> 0.05), which is not observed in the application of glutathione peroxidase, it is possible reception of glycine as a bisoprololum (p <0.05). This AA is a substrate of arginase - an cytoprotector in acute myocardial ischemia (MI) can lead to a enzyme that is present everywhere in living organisms, and decrease in lesion myocardial cells during hypoxia synthetize NO (Vorobets Z.D. et al, 2012) [2]. Therefore, these (Krasnenkova T.P. et al, 2014) [7]. Reducing the level of glycine changes may be interpreted as compensating destabilization in the blood serum of patients with UA during treatment with under the coronary circulation. nebivolol indicates an increase in intracellular metabolism of the It is essential to note that after the treatment of patients receiving AA, which means a protective response in a violation of the nebivolol, normal levels of taurine were observed as compared coronary circulation. to the CG (p> 0.05), and the patients receiving bisoprolol, the Revealed the same changes in alanine serum levels in both findings did not change significantly compared to either CG or groups after treatment. Patients taking bisoprolol, level of this in comparison to before treatment (both p <0.05). Taurine in AC significantly decreased as compared with before treatment myocardial amino acid constitute for about 50% (Kharchenko and CG respectively 14.48 mg / mol / 100 ml (p <0.05) and 5.16 N.V. et al, 2014) [10], hence the normalization of metabolism of mg / mole / 100ml (p 0, 05), and in patients whose therapy AA may be treated as a defensive response in terms of coronary included nebivolol respectively 23.72 mg / mol / 100 ml (p circulation disorders. <0.05) and 14.1 mg / mole / 100ml (p <0.05). The level of aspartic acid in the blood serum of both groups We also identified the same dynamic changes of serum levels of revealed no significant changes (all p> 0.05). cysteine in both groups after treatment. Patients taking Noteworthy is the fact that patient's antianginal therapy which bisoprolol, level of AA had increased significantly as compared include Nebivolol, serine levels increased significantly as with before treatment and 5.01 kg, respectively, in the u / mol / compared with before treatment to 1.56 mg / mol / 100 ml (p 100 ml (p <0.05), and 3.79 mg / mole / 100ml (p <0.05), and in <0.05), although it remained significantly lower at 3.25 u / mol patients whose therapy included nebivolol - by 3.62 mg / mol / / 100 ml compared to the CG (p <0.05). Patients taking 100 ml (p <0.05), and 2.4 mg / mol / 100 ml (p <0.05). bisoprolol, significant dynamics on the level of the AA did not UA patients taking bisoprolol, tyrosine level was significantly happen (all p <0.05). It should be noted that the form of the reduced by 3.92 mg / mol / 100 ml as compared with before serine protease serine - enzymes which, besides its other treatment (p <0.05) and 3.28 mg / mole / 100ml compared to the functions, play an important role in the blood coagulation CG (p < 0.05) and in patients whose therapy included nebivolol, cascade reactions. Members of this group of proteases are for the level of the AK was not significantly changed compared to example thrombin, trypsin, VIIa factors, IXa, Xa, XIa, XIIa, and the pre-treatment and compared to the CG (both p> 0.05). protein C. Therefore, this increase in the level of AA in serum Because tyrosine, with the participation of vitamins B and C, during treatment with nebivolol can improve the rheological folic and pantothenic acid, and a number of trace elements in the properties of the blood of patients with UA. human body is synthesized Coenzyme Q10. Coenzyme Q10 A significant increase in glutamic acid levels in UA patients effectively protects the lipids of biological membranes and receiving nebivolol compared to the pre-treatment at 5.72 mg / blood lipoprotein particles (phospholipids - "membrane glue") mol / 100 ml (p <0.05), although compared with the CG it from destructive processes peroxidation, DNA and protects the remains significantly lower at 5.97 microns / mol / 100 ml (p body from oxidative modification of proteins by the <0.05). UA patients, which includes therapy bisoprolol, accumulation of reactive oxygen species (Korovina N.A., Ruuhe glutamic acid levels did not change significantly as compared E.K., 2002) [6]. More than 20 years of experience in clinical trials with before treatment (p <0.05) and remained significantly of coenzyme Q10 in thousands of patients convincingly prove lower at 13.12 mg / mol / 100 ml compared to the CG (p <0, 05). his role in the pathology of cardiovascular deficiency, which is It is known that glutamic acid reacts with ammonia, converting not surprising, because in heart muscle cells the most large it to neutralize toxic glutamine. Also essential is that this energy needs. The protective role of coenzyme Q10 due to its increases the AA muscle cell membrane permeability to participation in the processes of energy metabolism and antioxidant properties of cardiomyocytes (Kapelko V.I., 2003) nebivolol can be regarded as a positive therapeutic effect in a [4]. Retention normal serum NS tyrosine patients when using destabilization of the coronary circulation. Table 1: The amino acid spectrum of blood serum in patients during treatment with UA, bisoprololum and nebilet Micromole/ 100ml (M ± m)
After the treatment.
After the treatment.
РІ-ІІ
РІ-ІІІ
treatment (І)
(Bisoprolol) (ІІ)
(Nebivolol) (ІІІ)
Р <0,05 Р <0,05 Р>0,05 Р <0,05 Р>0,05 Р>0,05 Р>0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р <0,05 Р>0,05 Р>0,05 Table 2: The amino acid spectrum of blood serum in patients during treatment with UA, bisoprololum and nebilet compared to the CG
Micromole / 100ml (M ± m) After the treatment
Amino Acids
Р (ІІ-ІІІ)
Bisoprolol Nebilet
It should be noted that patients in both treatment groups after 4. UA patients on antianginal therapy, including nebivolol treatment returned to normal levels of glutamine (both p <0.05). resist normal levels of tyrosine, which can serve as a UA patients, both study groups, antianginal therapy did not compensatory response in a destabilization of the coronary significantly affect the total amount of non-essential AA. After the treatment, the amount of nonessential AA remained 5. UA patients treated with antianginal therapy, which significantly lower compared to the CG, respectively, 28.6 mg / included bisoprolol and during treatment with antianginal mole / 100ml (p <0.05) and 40.8 mg / mole / 100ml (p <0.05). therapy, which included nebivolol, had normalized levels of Thus, the inclusion of anti-anginal therapy with nebivolol compared with bisoprololum effective influence in the correction of disorders of blood plasma amino acids levels in References
patients with UA. Bulanova EL, Drapkina OM. Nebivolol as inducer of nitric oxide synthesis. Difficult patient, 2014; 10:30-34. Conclusions
Vorobets ZD, Yefremova UP, Yakubets OI. Arginase 1. As a result of carried out treatment/study, no significant system in the human organism in the development of difference between the readings in the total amount of non- pathological processes. Clinical and Experimental essential AA were detected by the two groups of patients Pathology. 2012; XI,3(41),2:153-160. receiving nebivolol & bisoprolol Ivashkin VT, Drapkina OM. Clinical significance of nitric 2. UA patients receiving antianginal therapy with nebivolol, oxide and heat shock proteins. M.: GEOTAR-Media, had normalized the level of ornithine, AA which takes part in the disposal of ornithine cycle. Kapelko VI. Reactive oxygen species, antioxidants and 3. UA patients receiving nebivolol, normalized levels of prevention of heart diseases. Russian Medical Journal, taurine, has cardio-protective properties. With the usage of 2003; 11(21):1185-1188. bisoprololum, the level of this particular AA was not Kovalenko VM, Sirenko Yu M, Nesukai OH. The method significantly changed. of application nebilet for the treatment of cardiac insufficiency. Information letter Ministry of Healthcare of Ukraine, № 1, 2007. «Internal Medicine».- 2007; 1(1). Korovina NA, Ruuhe EK. The use of coenzyme Q10 in prevention and treatment. Application of the antioxidant drug Kudesan (Coenzyme Q10 with Vitamin E) in cardiology. Cardiology, 2002; 12:51-55. Krasnenkova TP, Yevseyenko AS, Kuvshinova NA. The efficiency of glycine at the experimental model of acute myocardial ischemia. Medical Journal. 2014; 2:70-73. Moshkovska Yu O. Nebivolol – a third generation β-blocker: the advantages and prospects of application in medical practice. Medicines Ukraine. 2015; 4(190):42-46. Nasyrova AG. Nitric oxide in the mechanisms of regulation of the pumping function of the heart in rats. Dissertation on completion. Art. MD Kazan. 2004, 131. 10. Kharchenko NV, Anokhina HA, Kharchenko VV. Peculiarities of nutrition patients with non-alcoholic steatohepatitis in combination with hypertrophic cardiomyopathy. The journal Health of Ukraine, 2014; 27(03):38-39. 11. Authors/Task Force Members, Mancia G, Fagard R, Narkiewicz K et al. ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013; 4(28):2159-219. 12. Brutsaert DL. Cardiac endothelial-myocardial signaling: its role in cardiac growth, contractile performance, and rhythmicity. Physiol. Rev. 2003; 83(1):59-115. 13. Chen S, Fu AC, Jain R, Tan H. Cardiovascular-related healthcare resource utilization and costs in patients with hypertension switching from metoprolol to nebivolol. Am. Health Drug Benefits. 2015; 8(2):71-80.

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