Cardioprotective Effectiveness of a Combination of 2-Ethyl-6-Methyl-3-Hydroxypyridine Enantiomers and Rosuvastatin in a Model of Doxorubicin Cardiomyopathy

Abstract

Aim. To study the cardioprotective effect of levorotatory ethylmethylhydroxypyridine malate enantiomer in combination with rosuvastatin on the model of doxorubicin cardiomyopathy.Material and methods. The research was conducted using 80 Langendorff perfused Wistar rat hearts (OOO “Kardioprotekt”, Saint-Petersburg) after a 3-day simulation of doxorubicin cardiomyopathy. The selection criteria for the evaluation of cardioprotective effect in the administration of ethylmethylhydroxypyridine derivatives and their combination with rosuvastatin were the indicators of left ventricular contractility, Tension-Time Index (t TTI), the diameter of cardiomyocytes.Results. During the experiment, it was found that the introduction of doxorubicin has a cardiotoxic effect, manifested through a decrease in the left ventricle contractility by 30–45% and an increase in the t TTI index by 4 times (“diastolic defect”). The introduction of a racemic mixture of ethylmethylhydroxypyridine malate at a dose of 93 mg/kg prevents the reduction of the left ventricle contractility and prevents the development of a “diastolic defect”, restraining the increase in the t TTI index by 32%, while the ethylmethylhydroxypyridine enantiomer at a dose of 93 mg/kg is more effective and its positive effect increases in combination with rosuvastatin at a dose of 0.4 mg/kg.Conclusion. The use of oxypyridine derivatives at doses of 50 mg/kg and 93 mg/kg, as well as their combination with rosuvastatin prevented the development of a “diastolic defect”. The highest effi ciency was revealed for the use of a combination of levorotatory ethylmethylhydroxypyridine malate enantiomer at a dose of 93 mg/kg with rosuvastatin at a dose of 0.4 mg/kg.

Keywords

• racemic mixture of ethylmethylhydroxypyridine malate enantiomers
• levorotatory ethylmethylhydroxypyridine malate enantiomer
• doxorubicin cardiomyopathy
• langendorf isolated heart
• “diastolic defect”