Endurance Training Protects Against Prostate Cancer Treatment-Induced Cardiac Dysfunction

Abstract

A common treatment for prostate cancer patients is the use of androgen deprivation therapy (ADT) in which testosterone is reduced to near-castrate levels using chemical gonadectomy agents. Surgical castration has been shown to impair cardiac function, however very little has been done investigating the effects of chemical castration on cardiac function. In addition, endurance training has been shown to be cardioprotective following surgical castration, but very little has been done investigating the effects of endurance training on cardiac function following chemical castration. PURPOSE: This study examined the effects of an 8-week ADT treatment using a leutenizing hormone releasing hormone (LHRH) agonist and endurance training regimen on cardiac function. To help explain possible mechanisms behind altered cardiac function, myosin heavy chain (MHC) composition was analyzed. METHODS: 10-week-old male Sprague-Dawley rats were randomly assigned to either sedentary (SED, n = 20) or exercise (EX, n = 20) groups. Animals were further randomly assigned to receive an 8-week LHRH agonist treatment (SED-ADT, n=10; EX-ADT, n=10) or placebo (SED-CON, n=10; EX-CON, n=10). Animals in the exercise groups trained on a motorized treadmill during the 8-week treatment period, and on day 57, ex vivo cardiac function and MHC isoform composition were analyzed. RESULTS: Hearts from SED-ADT had a significantly lower left ventricular developed pressure than hearts from SED-CON, EX-CON, and EX-ADT (62.5±1.7 mmHgvs. 77.8±0.8 mmHg, 80.1±2.0 mmHg, and 80.3±1.5 mmHg, respectively, p <0.05). There was a significantly slower rate of left ventricular relaxation in hearts from SED-ADT when compared to SED-CON, EX-CON, and EX-ADT (−1719±50 mmHg·s−1 vs. −2258±185 mmHg·s−1,-2059±53 mmHg·s−1, and −2231±82 mmHg·s−1, respectively, p <0.05). In addition, ventricles from SED-ADT expressed a significantly higher percentage of the β-MHC isoform than SED-CON, EX-CON, and EX-ADT (11.9±0.7% vs. 9.4±0.7%, 9.3±0.6%, and 8.7±0.7%, respectively, p <0.05). Androgen deprivation therapy using a LHRH agonist depressed cardiac function, and endurance training attenuated this depression. CONCLUSIONS: An 8-week treatment with a LHRH agonist promoted cardiac dysfunction which may be due to a ventricular α- to β-MHC isoform shift. Endurance training protected against this chemical castration-induced cardiac dysfunction. One possible mechanism behind the cardioprotection is an attenuation of the α- to β-MHC isoform shift associated with LHRH agonist treatment.