The dissertation is devoted to the study of pharmaco-toxicological effects of the newly developed drug «Bendamin», based on the inhibitor of phosphodiesterase-3 and ethylmethylhydroxypyridine succinate for use as a cardiac agent in dogs with heart failure.
A new cardiopharmaceutical «Bendamin» based on phosphodiesterase-3 inhibitor and ethylmethylhydroxypyridine succinate has been developed. For the first time, its pharmaco-toxicological evaluation was performed on laboratory animals and dogs. The effective dose of Bendamin was experimentally established and its effect on hematological and biochemical parameters of laboratory animals was studied. The parameters of acute and chronic toxicity, as well as the cumulative properties of Bendamin when administered intragastrically.
In the study of acute toxicity of the cardiac drug «Bendamin» to determine the value of DL50 failed, which indicates the low toxicity of the studied tool. Thus, the DL50 of the drug by intragastric administration to white mice and rats is more than 5000 mg/kg m. t.
According to studies on chronic toxicity of the drug, it was found that from the administration of white rats Bendamin in a therapeutic dose, as well as in 5 and 10 times the therapeutic dose, no visible clinical signs of drug intoxication were observed.
It was found that the introduction of the drug in 10-fold dose helped to reduce the body weight of white rats by 5 % compared with the control group.
The drug «Bendamin» in therapeutic and 5-fold doses contributed to a slight increase in the weight of the kidneys, while the introduction of the experimental drug in a much higher dose showed a decrease in the weight of the studied organs.
In rats treated with a 10-fold therapeutic dose of Bendamin, histodynamic disturbances and dystrophic changes, mainly of protein origin, with focal localization in the parenchyma of the liver, kidneys and myocardium, which in most cases are reversible and are the result of a compensatory reaction.
Based on experimental studies, we found that doxorubicin-induced cardiomyopathy is accompanied by a violation of the functional state of the body and changes in morphological and biochemical parameters of the blood of rats.
Doxorubicin intoxication in rats suppressed protein-synthesizing liver function, liver function. Under these conditions, a decrease in the activity of the antioxidant defense system of rats and intensification of lipid peroxidation processes.
The use of Vetmedin and Bendamin alleviated the manifestations of functional failure of the heart, liver and kidneys in conditions of doxorubicin intoxication. The best therapeutic effect in the case of doxorubicin intoxication was observed in experimental rats treated with the drug «Bendamin». Its normalizing effect on the hematological profile, functional state and protein-synthesizing function of the liver has been established.
The combined use of both active ingredients in Bendamin showed a clear tendency to improve all parts of the antioxidant system, both enzymatic and non-enzymatic, indicating the advantages of combining pimobendate with an antioxidant over the use of the drug with one active ingredient – pimobendan.
The use of the drug "Bendamin" almost completely eliminated all changes in the glutathione system in rats, under conditions of doxorubicin intoxication. It was found that the level of reduced glutathione in the blood of animals increased by 22.2 %, and in the myocardium – by 34.2 % relative to intoxicated rats.
The expediency of using the drug «Bendamin» in dogs with the development of heart failure has been scientifically substantiated and experimentally confirmed.
The use of cardiac drug «Bendamin» in patients with heart failure had a positive effect on the restoration of hematopoiesis and the normalization of morphological parameters of the blood. The use of the study drug alleviated the manifestations of functional failure of the heart, liver, and kidneys, as indicated by biochemical studies.
When using the drug «Bendamin» in dogs with clinical signs of heart failure, their blood activates the enzyme of the antioxidant system, as well as inhibition of pero oxidation of lipids.
Thus, the drug «Bendamin» has an antioxidant effect due to one of the components – ethylmethylhydroxypyridine succinate, which is an inhibitor of free radical processes, a membrane protector.
Our studies confirm the feasibility of using the drug «Bendamin» in dogs with the development of heart failure.
