Abstract
Bromide 1 - (β-phenylethyl)-4-amino-1,2,4-triazolium (Hypertril) has the properties of a beta-blocker and of NO-mimetic, is assigned to the IV class of toxicity. All these effects make Hypertril a promising drug for the treatment of cardiovascular diseases. The aim of this paper was to study the cardioprotective action of Hypertril in terms of the effect on the morpho-functional parameters of the myocardium in rats with experimental chronic heart failure (CHF). CHF was modeled on 80 white outbred rats weighing 190–220g by administering doxorubicin at a cumulative dose of 15 mg/kg. Hypertril and the reference drug metoprolol succinate were administered within 30 days after CHF modeling, intragastrically at doses of 3.5 mg/kg and 15 mg/kg. Morphometric analysis of the cellular structure of the myocardium was carried out on an Axioskop microscope (Zeiss, Germany), in an automatic mode using a macro program developed in a specialized programming environment VIDAS-2.5 (Kontron Elektronik, Germany). The administration of Hypertril to animals with CHF led to an increase in the density of nuclei of cardiomyocytes, the area of myocardiocyte nuclei, an increase in the nuclear cytoplasmic ratio and an increase in the concentration of RNA in the nuclei and cytoplasm of cardiomyocytes compared with the group of untreated animals, which indicated the presence of a pronounced cardioprotective effect in the drug candidate. In terms of such indicators as the density of surviving cardiomyocytes and the content of RNA in them, the nuclear-cytoplasmic ratio of Hypertril is significantly (p < 0.05) superior to metoprolol.
Highlights
The beginning of the current millennium was marked by a significant spread of cardiovascular diseases, which ranked 2–3 in the structure of mortality in industrialized countries
Our description of the morphological picture of the myocardium in experimental animals does not contradict the results of other researchers working with this model
According to the data and results of other researchers (Khloponin 2009; Mazur et al 2010), mononuclear cardiomyocytes retain the ability to enter the cell cycle, which ends with karyokinesis, which leads to a decrease in their number and, to an increase in the pool of binuclear cells
Summary
The beginning of the current millennium was marked by a significant spread of cardiovascular diseases, which ranked 2–3 in the structure of mortality in industrialized countries. One of the formidable complications, mortality from which ranges from 10% to 50% in patients with cardiovascular pathology, is chronic heart failure (CHF). According to the recommendations of the European Community of Cardiology, diuretics, ACE inhibitors and β-blockers are important components of the complex therapy of heart failure, especially after myocardial infarction. The foregoing served as a rationale for the creation of a new drug of the original structure (bromide 1 - (β- phenylethyl) -4-amino-1,2,4-triazolium, working title Hypertril) which has NO-mimetic, β1-adrenergic blocking, antihypertensive, anti-ischemic action and belongs to the IV class of toxicity (LD50 is 683.4 mg/kg with intragastric administration to rats) (Mazur et al 2010,2019; Chekman et al 2013).
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