Influence of experimental heart failure therapy with different generations of β-adrenergic blockers on Cardiac Electrical Activity (ECG) and Autonomic Regulation of Heart Rhythm (ARHR)

Abstract

Abstract: In the complex treatment of chronic heart failure (CHF) β-adrenoblockers (carvedilol, nebivolol, bisoprolol, metoprolol) are used, which due to their pharmacological properties increase the survival rate of patients, improve cardio- and haemodynamic parameters, metabolism. However, modern realities in medicine require creation of new more effective and safe β-adrenoblockers. In this regard, the potential drug Hypertirl is of interest. The aim was to evaluate the cardioprotective effect of 1-(b-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril) on cardiac electrical activity and autonomic regulation of heart rhythm in a model of CHF in comparison with β-adrenoblockers of different generations (Nebivolol, Carvedilol, Bisoprolol, Metoprolol). Materials and methods: Chronic heart failure was induced by 14-day administration of doxorubicin in a cumulative dose of 15 mg/kg to white mongrel rats weighing 190–220g (total 85). The investigated drugs were administered after doxorubicin course for 30 days: Hypertril at an experimentally substantiated dose of 3.5 mg/kg, Metoprolol succinate 15 mg/kg, Nebivolol 10 mg/kg, Carvedilol 50 mg/kg, Bisoprolol 10 mg/kg. At the end of drug administration under thiopental anaesthesia (40 mg/kg), electrocardiogram (ECG) and autonomic regulation of heart rhythm (ARHR) were analysed using a computer analyser CardioCom-2000plus (KAI-Medica, Ukraine). The results of the study were calculated using a standard statistical package “STATISTICA for Windows 6.0” (StatSoftInc., №AXXR712D833214FAN5), “SPSS 16.0” and “Microsoft Office Excell 2003”. Results and discussion: Hypertril administration resulted in a negative chronotropic effect, normalisation of atrial (P) and ventricular (R) spike amplitude, ST segment inversion below isoline, increased amplitude of ventricular myocardial repolarisation T. Myocardial repolarisation spike were observed, as well as normalised the duration of atrial (P) and ventricular depolarisation phase (QRS complex) to the intact value and restored the duration of electrical diastole (TR interval). Hypertril reduced systolic and diastolic myocardial dysfunction in animals with CHF. Hypertril restored autonomic mechanisms of heart rhythm regulation and balanced activity of sympathetic and parasympathetic parts of autonomic nervous system in the control of cardiac function. Conclusion: The obtained results demonstrated the undoubted advantage of the new original molecule (Hypertril) over basic β-adrenoblockers (Metoprolol, Nebivolol, Carvedilol and Bisoprolol) and experimentally justify further in-depth study to create on its basis a drug for the treatment of CHF.