PURPOSE: Doxorubicin (DOX) and goserelin acetate (GA), when administered individually, can lead to impaired cardiac function via different mechanisms. Combining GA and DOX (GA + DOX), however, could potentially exacerbate cardiac dysfunction when compared to GA and DOX treatments administered individually. Therefore, the first purpose of this study was to investigate the effects of GA + DOX on cardiac function. Additionally, since exercise training has been shown to protect against GA- and DOX-induced cardiac dysfunction when administered individually, the second purpose of this study was to examine the effects of exercise during GA + DOX on cardiac function. METHODS: Female rats were randomly assigned to control (CON), GA, DOX, GA + DOX, or exercise training during GA + DOX (EX GA + DOX). Following 56 days, cardiac function was analyzed in vivo using echocardiography and ex vivo using an isolated working heart model. RESULTS: GA + DOX had significantly lower mitral valve maximal and mean blood flow velocities and aortic valve maximal blood flow velocity than CON (in vivo analysis, P < 0.05), but these differences were not observed between EX GA + DOX and CON. In the isolated working heart, GA + DOX hearts had significantly different left ventricular developed pressures and maximal rates of pressure development and decline than CON (P < 0.05), but these differences were not observed in EX GA + DOX. CONCLUSIONS: GA + DOX resulted in significantly impaired in vivo and ex vivo cardiac function, but exercise training during GA + DOX was cardioprotective.
PURPOSE:Doxorubicin (DOX) and goserelin acetate (GA), when administered individually, can lead to impaired cardiac function via different mechanisms. Combining GA and DOX (GA + DOX), however, could potentially exacerbate cardiac dysfunction when compared to GA and DOX treatments administered individually. Therefore, the first purpose of this study was to investigate the effects of GA + DOX on cardiac function. Additionally, since exercise training has been shown to protect against GA- and DOX-induced cardiac dysfunction when administered individually, the second purpose of this study was to examine the effects of exercise during GA + DOX on cardiac function. METHODS: Female rats were randomly assigned to control (CON), GA, DOX, GA + DOX, or exercise training during GA + DOX (EX GA + DOX). Following 56 days, cardiac function was analyzed in vivo using echocardiography and ex vivo using an isolated working heart model. RESULTS: GA + DOX had significantly lower mitral valve maximal and mean blood flow velocities and aortic valve maximal blood flow velocity than CON (in vivo analysis, P < 0.05), but these differences were not observed between EX GA + DOX and CON. In the isolated working heart, GA + DOX hearts had significantly different left ventricular developed pressures and maximal rates of pressure development and decline than CON (P < 0.05), but these differences were not observed in EX GA + DOX. CONCLUSIONS: GA + DOX resulted in significantly impaired in vivo and ex vivo cardiac function, but exercise training during GA + DOX was cardioprotective.
Authors: Willeke R Naaktgeboren; David Binyam; Martijn M Stuiver; Neil K Aaronson; Arco J Teske; Wim H van Harten; Wim G Groen; Anne M May Journal: J Am Heart Assoc Date: 2021-09-02 Impact factor: 5.501