New antianginal medication «Gipertril» (ÌÒ) (derivative of 4-amino-1,2,4-triazole), product of Scientific Production Association “Pharmatron” (president – professor I.A. Mazur) due to cardioprotective mechanisms directed on the decrease of both preload and post-load on heart improves indexes of the system hemodynamics and heart hemodynamics in the conditions of acute myocardial ischemia (AMI). AMI was induced in outbred rabbits by intravenous injection of caffeine – sodium benzoate solution in dose 25 mg/kg and then 3 minutes later adrenaline hydrochloride was introduced intravenously at the rate of 0,2 mg of pure adrenaline per kg. Intravenous introduction of «Gipertril» to the rabbits with AMI in the dose of 2,5 mg/kg 30 min before introduction of caffeine – benzoate resulted in significant decrease of general peripheral vascular resistance (GPVR) by 30% as compared with the control group that testifies to vasodilating effect of this medication.
Introduction of metoprolol as opposed to «Gipertril» increased GPVR in animals with AMI. In groups of animals, which received «Gipertril» and metoprolol, decrease of heart rate was noted that is the medication showed negative chronotropic effect typical of all -adrenoceptor antagonists, decreasing pre-load on heart in the period of acute ischemia. In the group which received «Gipertril» heart rate was significantly lower by 27% over all period of the experiment as compared with the control group. In the group which received metoprolol heart rate was significantly lower by 24% as compared with the control values. «Gipertril» introduction resulted in significant increase of stroke volume (SV) by 20–23%% on 15–30th minutes of myocardial ischemia. At the same time significant increase of cardiac index (CI) by 26–22%% (15th and 30th minutes of myocardial ischemia correspondingly) was recorded as compared with the group of untreated animals as well as increase of stroke volume index (SVI) by 37% and 22% at the proper moments of registration. «Gipertril» and metoprolol influenced with different intensity on minute blood volume (MBV) in AMI. In AMI experimental group, which received metoprolol, significant decrease of MBV was observed as compared with the control group data on 15th and 30th minutes of the experiment (by 27% and 29% correspondingly).
Animals with AMI which received «Gipertril» did not show significant MBV changes as compared with untreated animals (tendency to decrease).
Introduction of «Gipertril» to AMI animals resulted in normalization of heart activity increasing the values of left ventricular work index (LVSI) and left ventricular stroke work index (LVSWI) during 30 minutes of the experiment in measures of 38,6–51%% and 53,3–62,4%% correspondingly. Introduction of metoprolol to AMI animals resulted in depression of LVSI as compared with the control group. LVSWI in AMI animals against background of metoprolol administration was on average by 26% lower than in the control group and by 55–57%% lower than value in intact animals. Introduction of «Gipertril» under AMI resulted also in normalization of such parameter of heart functional activity as left ventricle pressure, increasing it up to the healthy animals’ values. The reference medication metoprolol did not influence significantly on this value.
Cardioprotective action of the reference medication «Metoprolol» (10 mg/kg) is connected generally with diminishing of pre-loading on the heart.
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