goserelin and Heart-Diseases

Doxorubicin (DOX) is associated with cardiac dysfunction and irreversible testicular damage. Androgen deprivation therapy (ADT) is administered prior to DOX treatment to preserve testicular function. However, ADT may exacerbate DOX-induced cardiac dysfunction. Exercise is cardioprotective, but the effects of exercise on cardiac function during combined ADT and DOX treatment are currently unknown. In this study, male Sprague-Dawley rats were randomly assigned to experimental groups: control (CON), ADT, DOX, or ADT+DOX. Animals received ADT or control implants on days 1 and 29 of the 56-day protocol. Animals remained sedentary (SED) or engaged in treadmill endurance exercise (TM) beginning on day 1. On day 15, the animals received DOX at 1 mg·(kg body mass)(-1)·d(-1) by intraperitoneal injection for 10 consecutive days, or an equivalent volume of saline. On day 57, cardiac function was assessed in vivo and ex vivo. Animals treated with DOX alone, or with combined ADT+DOX, showed significant (P < 0.05) reductions in left ventricular developed pressure (-21% and -27%), maximal rate of pressure development (-29% and -32%), and maximal rate of pressure decline (25% and 31%), respectively when compared with the sedentary control animals. Endurance exercise training attenuated (P > 0.05) cardiac dysfunction associated with combined ADT+DOX treatment, indicating that exercise during simultaneous ADT+DOX treatment is cardioprotective.

Topics: Androgens; Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Doxorubicin; Goserelin; Heart Diseases; Luteinizing Hormone; Male; Myosin Heavy Chains; Physical Conditioning, Animal; Random Allocation; Rats, Sprague-Dawley

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.. 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.. 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.. GA + DOX resulted in significantly impaired in vivo and ex vivo cardiac function, but exercise training during GA + DOX was cardioprotective.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Hormonal; Aortic Valve; Blood Pressure; Body Weight; Doxorubicin; Drug Implants; Female; Goserelin; Heart Diseases; Heart Function Tests; Mitral Valve; Organ Size; Physical Conditioning, Animal; Physical Endurance; Rats; Rats, Sprague-Dawley; Ultrasonography; Ventricular Function, Left