ABSTRACT
Exercise preconditioning has been shown to protect against DOX-induced cardiac dysfunction when hearts are maintained under resting conditions. However, it is unclear whether this exercise-induced protective effect is maintained when the heart is challenged with the ß1-adrenergic receptor agonist dobutamine (DOB), which mimics acute exercise stress. Fischer 344 rats were randomly assigned to sedentary (SED) or voluntary wheel running (WR) groups for 10 weeks. At week 11, rats were treated with either 15 mg/kg DOX or saline (SAL). Five days later, ex vivo cardiac function was assessed using an isolating working heart model at baseline, during the infusion of 7.5 µg/kg/min DOB, and during recovery. DOB infusion significantly increased left ventricular developed pressure (LVDP), maximal (dP/dtmax) and minimal (dP/dtmin) rate of left ventricular pressure development, and heart rate in all groups (p<0.05). SED+DOX also showed a lower baseline and recovery LVDP than WR+DOX (83 ± 12 vs. 109 ± 6 mmHg baseline, 76 ± 11 vs. 100 ± 10 mmHg recovery, p<0.05). WR+DOX showed higher dP/dtmax and lower dP/dtmin when compared to SED+DOX during DOB infusion (7311 ± 1481 vs. 5167 ± 1436 mmHg/s and -4059 ± 1114 vs.-3158 ± 1176 mmHg/s, respectively). SED+DOX dP/dtmax was significantly lower during baseline and during recovery when compared to all other groups (p<0.05). These data suggest that exercise preconditioning preserved cardiac function after DOX exposure even when the heart is challenged with DOB, and it appeared to preserve the heart's ability to recover from this functional challenge.
ABSTRACT
BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).
