Echocardiographic assessment of the structural and functional state of the heart and the cardioprotective effects of mesenchymal stem cell conditioned medium in combined doxorubicin and celecoxib cardiotoxicity

Main Article Content

I. H. Drobner
F. V. Hladkykh
V. O. Student
Т. І. Liadova
M. S. Matvieienko
Т. V. Rubleva

Abstract

The aim – to perform an echocardiographic assessment of structural and functional cardiac alterations in combined doxorubicin- and celecoxib-induced cardiomyopathy and to determine the cardioprotective efficacy of mesenchymal stem cell-conditioned medium.
Materials and methods. The study was conducted in 28 rats with experimentally induced doxorubicin- and celecoxib-associated cardiomyopathy. Echocardiographic evaluation of left ventricular morphometric, volumetric, and functional parameters was performed. The cardioprotective effects of mesenchymal stem cell–conditioned medium were compared with those of carvedilol using parametric and nonparametric statistical analyses.
Results and discussion. Combined doxorubicin and celecoxib exposure resulted in marked left ventricular dilatation, with a 27.7 % increase in end-diastolic volume (p=0.049) and a 194.5 % increase in end-systolic volume (p<0.001) compared with intact animals. Myocardial mass increased by 11.9 % (p=0.002), while fractional shortening and ejection fraction decreased by 51.3 % and 41.2 %, respectively (p<0.001). Carvedilol reduced end-systolic volume by 56.9 % and increased fractional shortening by 90.7 % (p<0.001). Mesenchymal stem cell-conditioned medium provided a more profound correction, reducing end-diastolic volume by 22.1 % (p=0.004) and end-systolic volume by 60.1 % (p<0.001), normalizing end-diastolic diameter, and increasing interventricular septal systolic thickening by 109.5 % (p=0.028).
Conclusions. The combined cardiotoxic effects of doxorubicin and celecoxib induce severe dilatational and systolic cardiac remodeling. Mesenchymal stem cell-conditioned medium exerts a robust cardioprotective effect, surpassing carvedilol in the depth of echocardiographic normalization and restoration of myocardial contractile function.

Article Details

Keywords:

doxorubicin, celecoxib, mesenchymal stem cells, ejection fraction, stroke volume, cardiac output, ultrasound

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