Cancer type does not affect exercise-mediated improvements in cardiorespiratory function and fatigue.

PURPOSE: Despite mounting evidence indicating that exercise training has a positive effect on cancer recovery, the influence of cancer type on the response to exercise training remains uncharacterized. Therefore, the adaptations to exercise training were compared between groups composed of 7 different forms of cancer. METHODS: A total of 319 cancer survivors completed fatigue inventories and participated in assessments of cardiorespiratory function, which encompassed aerobic capacity (VO2 peak), pulmonary function (forced vital capacity [FVC] and forced expiratory volume in 1 second [FEV1]), and resting blood pressure and heart rate. Participants were divided into 7 groups based on cancer type, including breast cancer (BC, n = 170), prostate cancer and other male urogenital neoplasia (PC, n = 38), hematological malignancies (HM, n = 34), colorectal cancer (CC, n = 25), gynecological cancers (GC, n = 20), glandular and epithelial neoplasms (GEN, n = 20), and lung cancer (LC, n = 12). All participants completed an individualized, multimodal exercise intervention consisting of cardiorespiratory, flexibility, balance, and muscular strength training 3 days per week for 3 months. Following the intervention, all subjects were reassessed. Generalized Estimating Equations with exchangeable working correlation structure was used to model each response; the group by time interaction effect represented the effect of cancer type on exercise-associated improvements. RESULTS: No significant (P > .05) group by time interaction effects were observed between different types of cancer for any parameter. Pre- to postexercise contrasts revealed significant improvements in VO2 peak in BC, PC, HM, and GEN at the Bonferroni adjusted significance level (.00714). Heart rate was significantly lowered in the BC and CC groups. Mean fatigue indices decreased by at least 17% in all groups, but these changes were only significant in the BC, HM, CC, and GC groups. Systolic blood pressure decreased significantly in BC and GC, and diastolic blood pressure decreased significantly only in the BC group while pulmonary function remained unchanged in all cancer types. CONCLUSION: Although trends toward improved cardiorespiratory and fatigue parameters only reached significance in some groups, there were no significant differences between cancer types. This suggests that cardiorespiratory and fatigue improvements following rehabilitative exercise are not dependent on cancer type. Further research investigating alternative physiological parameters are needed to confirm the relationship between cancer type and exercise-mediated rehabilitation.

Endurance exercise attenuates cardiotoxicity induced by androgen deprivation and doxorubicin.

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.

Transcriptomic analysis of murine embryos lacking endogenous retinoic acid signaling.

Retinoic acid (RA), an active derivative of the liposoluble vitamin A (retinol), acts as an important signaling molecule during embryonic development, regulating phenomenons as diverse as anterior-posterior axial patterning, forebrain and optic vesicle development, specification of hindbrain rhombomeres, pharyngeal arches and second heart field, somitogenesis, and differentiation of spinal cord neurons. This small molecule directly triggers gene activation by binding to nuclear receptors (RARs), switching them from potential repressors to transcriptional activators. The repertoire of RA-regulated genes in embryonic tissues is poorly characterized. We performed a comparative analysis of the transcriptomes of murine wild-type and Retinaldehyde Dehydrogenase 2 null-mutant (Raldh2 (-/-)) embryos - unable to synthesize RA from maternally-derived retinol - using Affymetrix DNA microarrays. Transcriptomic changes were analyzed in two embryonic regions: anterior tissues including forebrain and optic vesicle, and posterior (trunk) tissues, at early stages preceding the appearance of overt phenotypic abnormalities. Several genes expected to be downregulated under RA deficiency appeared in the transcriptome data (e.g. Emx2, Foxg1 anteriorly, Cdx1, Hoxa1, Rarb posteriorly), whereas reverse-transcriptase-PCR and in situ hybridization performed for additional selected genes validated the changes identified through microarray analysis. Altogether, the affected genes belonged to numerous molecular pathways and cellular/organismal functions, demonstrating the pleiotropic nature of RA-dependent events. In both tissue samples, genes upregulated were more numerous than those downregulated, probably due to feedback regulatory loops. Bioinformatic analyses highlighted groups (clusters) of genes displaying similar behaviors in mutant tissues, and biological functions most significantly affected (e.g. mTOR, VEGF, ILK signaling in forebrain tissues; pyrimidine and purine metabolism, calcium signaling, one carbon metabolism in posterior tissues). Overall, these data give an overview of the gene expression changes resulting from embryonic RA deficiency, and provide new candidate genes and pathways that may help understanding retinoid-dependent molecular events.

Exercise mitigates cardiac doxorubicin accumulation and preserves function in the rat.

PURPOSE: Doxorubicin (DOX) is an effective antineoplastic agent with well-characterized cardiotoxic effects. Although exercise has been shown to protect against DOX cardiotoxicity, a clear and concise mechanism to explain its cardioprotective effects is lacking. The purpose of this study was to determine if exercise training reduces cardiac DOX accumulation, thereby providing a possible mechanism to explain the cardioprotective effects of exercise against DOX toxicity. METHODS: Sprague-Dawley rats were randomly assigned to 1 of 3 primary experimental groups: sedentary (n = 77), wheel running (n = 65), or treadmill (n = 65). Animals in wheel running and treadmill groups completed 10 weeks of exercise before DOX treatment. DOX was administered 24 hours after the last training session as a bolus intraperitoneal injection at 10 mg/kg. Subgroups of rats from each primary group were killed at 1, 3, 5, 7, and 9 days after DOX exposure to assess cardiac function and DOX accumulation. RESULTS: Ten weeks of exercise preconditioning reduced myocardial DOX accumulation, and this reduction in accumulation was associated with preserved cardiac function. CONCLUSIONS: These data suggest that the cardioprotective effects of exercise against DOX-induced injury may be due, in part, to a reduction in myocardial DOX accumulation.

Switching to a low-fat diet attenuates the intensified doxorubicin cardiotoxicity associated with high-fat feeding.

PURPOSE: A high-fat diet has been shown to exacerbate the cardiotoxicity associated with the chemotherapy drug doxorubicin (DOX); however, it is unknown whether switching from a high-fat diet to a low-fat diet can attenuate the intensified DOX cardiotoxicity. The purpose of this study was to investigate the effects of a low-fat diet on DOX-induced cardiotoxicity in rats previously fed a high-fat diet. METHODS: Male rats were randomly assigned to consume a Western diet or a low-fat diet for 6 weeks. Western diet-fed rats were then further randomized to switch to the low-fat diet (WD-LF) or continue with the Western diet (WD). One week later, WD-LF and WD received 1 mg/kg DOX per day for 10 consecutive days and continued with their diets (WD-LF + DOX, WD + DOX). LF was further randomized to receive 1 mg/kg DOX per day for 10 consecutive days (LF + DOX) or saline injections as a control (LF + SAL). Four weeks following the first injection, cardiac function was analyzed, and left ventricles were analyzed for cardiotoxicity indices. RESULTS: When compared to LF + SAL and LF + DOX, WD + DOX exhibited an enhanced cardiotoxicity as evidenced by reduced septal wall thickness, fractional shortening, and sarco-endoplasmic reticulum Ca(2+) ATPase expression as well as increased left ventricular cavity dimensions, lipid peroxidation, and ß-myosin heavy-chain expression. This exacerbated cardiotoxicity was not observed in WD-LF + DOX. CONCLUSIONS: Switching to a low-fat diet 1 week prior to, during, and following DOX treatment attenuated the exacerbated cardiotoxicity observed in the previously Western diet-fed rats.

Voluntary wheel running in growing rats does not protect against doxorubicin-induced osteopenia.

There is growing concern regarding the long-term negative side effects of chemotherapy in childhood cancer survivors. Doxorubicin (DOX) is commonly used in the treatment of childhood cancers and has been shown to be both cardiotoxic and osteotoxic. It is unclear whether exercise can attenuate the negative skeletal effects of this chemotherapy. Rat pups were treated with saline or DOX. Animals remained sedentary or voluntarily exercised. After 10 weeks, femoral bone mineral content and bone mineral density were measured using dual-energy x-ray absorptiometry. Cortical and cancellous bone architecture was then evaluated by microcomputed tomography. DOX had a profound negative effect on all measures of bone mass and cortical and cancellous bone architecture. Treatment with DOX resulted in shorter femora and lower femoral bone mineral content and bone mineral density, lower cross-sectional volume, cortical volume, marrow volume, cortical thickness, and principal (IMAX, IMIN) and polar (IPOLAR) moments of inertia in the femur diaphysis, and lower cancellous bone volume/tissue volume, trabecular number, and trabecular thickness in the distal femur metaphysis. Exercise failed to protect bones from the damaging effects of DOX. Other modalities may be necessary to mitigate the deleterious skeletal effects that occur in juveniles undergoing treatment with anthracyclines.

Rehabilitative exercise in a rat model of doxorubicin cardiotoxicity.

The use of exercise to minimize doxorubicin (DOX)-induced cardiotoxicity is gaining attention. However, very few clinically relevant reports exist investigating the effects of exercise performed during and following DOX treatments. The purpose of this study, therefore, was to examine the effects of voluntary wheel running during and following DOX treatment using two models of late-onset DOX cardiotoxicity in the rat. Female Sprague-Dawley rats received either DOX or saline injections using one of two separate treatment regimens. These regimens involved either daily or weekly DOX injections with cumulative doses for both protocols totaling 15 mg/kg. Daily DOX injections were 1 mg/kg and lasted for 15 consecutive days while weekly DOX injections were 2.5 mg/kg and lasted for six consecutive weeks with control animals receiving matched saline injection regimens. Immediately following the initial DOX/saline injection, animals were randomly housed in cages with voluntary running wheels or standard rat cages throughout DOX/saline treatments and continued until reaching 10 weeks. Cardiac function was then assessed using echocardiography and an isolated working heart model, and myosin heavy chain (MHC) isoform distribution was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When compared wth controls, daily DOX treatment resulted in reduced running wheel distances at weeks 2-10 (P < 0.05), and weekly DOX treatment resulted in reduced running wheel distances at weeks 2, 6 and 10 (P < 0.05). Nonetheless, wheel running during and following daily and weekly DOX dosing protected against DOX-induced cardiotoxicity by preserving maximal mitral and aortic blood flow velocities, left ventricular developed pressure and MHC isoform expression. In conclusion, the overall reduced volume of activity during and following daily and weekly DOX treatments attenuated DOX-induced cardiac dysfunction suggesting that low-volume endurance training may be an effective rehabilitative approach in minimizing DOX cardiotoxicity in cancer patients.

Exercise training mitigates anthracycline-induced chronic cardiotoxicity in a juvenile rat model.

BACKGROUND: Childhood cancer survivors are at greater risk of cardiovascular complications once they reach adulthood. Anthracyclines may be a major contributor to these delayed-onset complications, yet their use continues because of favorable clinical outcomes. Exercise has been shown to protect against anthracycline cardiotoxicity, yet it is unclear whether exercise can protect against delayed-onset cardiotoxicity when treatment is initiated in childhood. The aim of the present study was to determine if exercise training provides cardioprotection in a juvenile rat model of delayed-onset anthracycline cardiotoxicity. PROCEDURE: At 25 days of age, male Sprague-Dawley rat pups were subjected to a treatment regimen with the anthracycline doxorubicin (DOX). Pups received DOX at 2 mg/kg on 7 consecutive days (cumulative dose 14 mg/kg) or saline as a control. At the time DOX treatment began, pups remained sedentary or were allowed to voluntarily exercise. Ten weeks after the initiation of exercise, cardiac function was assessed both in vivo and ex vivo. RESULTS: DOX treatment stunted normal growth and significantly impaired cardiac function. While voluntary exercise did not offset changes in the growth curve, it did provide significant cardioprotection against DOX-induced cardiotoxicity. CONCLUSIONS: Exercise training, initiated at the time treatment begins, can protect against delayed-onset anthracycline-induced cardiotoxicity in adult rats that were treated with anthracyclines as juveniles.

Characterization of the effect of in vivo doxorubicin treatment on skeletal muscle function in the rat.

UNLABELLED: Doxorubicin (DOX)-induced muscle dysfunction may contribute to patient fatigue, but the nature of this myotoxicity remains unclear. The purpose of this study was to characterize the muscle function dose-response to DOX. A secondary purpose was to compare the degree of DOX-induced muscle dysfunction to the observed cardiac dysfunction. MATERIALS AND METHODS: Rats received DOX at 10 mg/kg (DOX1), 12.5 mg/kg (DOX2), or 15 mg/kg (DOX3). Muscle and cardiac function were assessed 5 days, post injection. RESULTS: Compared to controls, DOX2 and DOX3 soleus and DOX3 extensor digitorum longus (EDL) had lower maximal twitch force (p<0.05). Soleus fatigue rate was altered by DOX, but EDL fatigue rate was not. Additionally, fractional shortening was lower in DOX2 and DOX3 compared to controls (p<0.05). CONCLUSION: DOX impaired muscle function in a dose-dependent manner. The degree of dysfunction was greater in the soleus and was consistent with the observed cardiac dysfunction.

Exercise preconditioning provides long-term protection against early chronic doxorubicin cardiotoxicity.

Acute doxorubicin (DOX) cardiotoxicity can be attenuated by exercise preconditioning, but little is known of whether this cardioprotection continues beyond 10 days post-DOX administration. The purpose of this study was to determine the effects of exercise preconditioning on early chronic DOX-induced cardiotoxicity. Male rats were randomly assigned to sedentary, treadmill, or wheel running groups. Treadmill and wheel running animals participated in a progressive treadmill training protocol or voluntary wheel running, respectively, for 10 weeks. Following the intervention, animals were further randomized to receive either DOX (sedentary + DOX, treadmill + DOX, wheel running + DOX) or saline (sedentary + saline, treadmill + saline, wheel running + saline). All animals then remained sedentary for 4 weeks. A 22% reduction in fractional shortening was observed in left ventricles from previously sedentary animals receiving DOX when compared with sedentary + saline. This degree of decline was not observed in treadmill + DOX and wheel running + DOX. Sedentary + DOX possessed significantly depressed mitral and aortic valve blood flow velocities when compared with sedentary + saline, but these decrements were not observed in treadmill + DOX and wheel running + DOX. Ex vivo analysis revealed that left ventricular developed pressure and maximal rate of pressure development were significantly lower in sedentary + DOX when compared to sedentary + saline. Treadmill and wheel running prior to DOX treatment protected against these decrements. Exercise cardioprotection was associated with preserved myosin heavy chain but not sarcoendoplasmic reticulum Ca(2+) ATPase 2a expression. In conclusion, 10 weeks of prior exercise protected against early chronic DOX cardiotoxicity suggesting that training status may be a determining factor in the degree of late-onset cardiotoxicity experienced by cancer patients undergoing treatment with DOX.

Effects of endurance training on combined goserelin acetate and doxorubicin treatment-induced cardiac dysfunction.

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.

American College of Sports Medicine roundtable on exercise guidelines for cancer survivors.

Early detection and improved treatments for cancer have resulted in roughly 12 million survivors alive in the United States today. This growing population faces unique challenges from their disease and treatments, including risk for recurrent cancer, other chronic diseases, and persistent adverse effects on physical functioning and quality of life. Historically, clinicians advised cancer patients to rest and to avoid activity; however, emerging research on exercise has challenged this recommendation. To this end, a roundtable was convened by American College of Sports Medicine to distill the literature on the safety and efficacy of exercise training during and after adjuvant cancer therapy and to provide guidelines. The roundtable concluded that exercise training is safe during and after cancer treatments and results in improvements in physical functioning, quality of life, and cancer-related fatigue in several cancer survivor groups. Implications for disease outcomes and survival are still unknown. Nevertheless, the benefits to physical functioning and quality of life are sufficient for the recommendation that cancer survivors follow the 2008 Physical Activity Guidelines for Americans, with specific exercise programming adaptations based on disease and treatment-related adverse effects. The advice to "avoid inactivity," even in cancer patients with existing disease or undergoing difficult treatments, is likely helpful.

Three versus six months of exercise training in breast cancer survivors.

Breast cancer is the most prevalent type of cancer in American women. Exercise appears to diminish many of the side effects resulting from breast cancer and its treatment. Very little research, however, has compared the outcomes of varying lengths of combined aerobic and resistance training exercise interventions on physiological and psychological parameters in breast cancer survivors. The purpose of this study was to compare the physiological and psychological outcomes following 3 and 6 months of exercise in breast cancer survivors. Breast cancer survivors (N = 114) participated in either 3 months of prescriptive, individualized exercise (3M; n = 29), 6 months of prescriptive, individualized exercise (6M; n = 68), or served as sedentary controls (C; n = 17). Cancer survivors completed a medical evaluation and assessment at baseline followed by a predetermined 3- or 6-month exercise intervention. Cancer survivors in the control group performed no exercise between the initial assessment and 6-month reassessment. Cardiovascular endurance, pulmonary function, muscular endurance, fatigue, and symptoms of depression were assessed at baseline and post intervention. Repeated measures ANCOVA revealed improvements (P < 0.05) in cardiovascular endurance, fatigue, and symptoms of depression in breast cancer survivors undergoing 3- and 6-month individualized exercise interventions. Breast cancer survivors exercising for 6 months showed additional improvements (P < 0.05) in pulmonary function and muscular endurance. Cancer survivors in the control group did not improve in cardiovascular endurance, pulmonary function, muscular endurance, or fatigue. Three months of individualized, prescriptive exercise leads to improved cardiovascular endurance, fatigue, and symptoms of depression in breast cancer survivors. Additional benefits are seen if exercise is continued for a total of 6 months.

Voluntary wheel running in rats receiving doxorubicin: effects on running activity and cardiac myosin heavy chain.

BACKGROUND: The clinical use of the highly effective chemotherapeutic agent doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. This cardiotoxicity is associated with a cardiac myosin heavy chain (MHC) isoform shift from the alpha isoform to the beta isoform. Exercise prior to DOX treatment has been shown to attenuate the MHC shift associated with DOX, but little is known about the cardioprotective nature of exercise during DOX treatment. MATERIALS AND METHODS: DOX-treated rats were assigned to normal cage activity (sedentary, SED+DOX) or 24-hour voluntary wheel running access (WR+DOX). All animals received weekly 2.5 mg/kg DOX injections for 6 weeks (15 mg/kg cumulative) and hearts were subsequently excised for determination of MHC isoform expression using sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: At baseline, WR+DOX rats on average ran 62+/-4 km, and at week 6 ran 30+/-5 km, which was significantly lower than baseline (p<0.05). SED+DOX hearts expressed 57+/-7% of MHC as the alpha-MHC isoform and 43+/-7% as the beta-MHC isoform. WR+DOX hearts expressed 76+/-4% as the alpha-MHC and 24+/-4% as the beta-MHC isoform, which was significantly different from that of SED+DOX (p<0.05). CONCLUSION: DOX treatment significantly reduced wheel running activity, but this reduced running distance deemed to be cardioprotective as hearts from WR+DOX rats contained significantly greater levels of the favorable alpha-MHC isoform than SED+DOX.

Endurance exercise training preserves cardiac function in rats receiving doxorubicin and the HER-2 inhibitor GW2974.

PURPOSE: To determine if endurance exercise training performed prior to administration of the anticancer drugs DOX and GW2974 would be cardioprotective. METHODS: Rats remained sedentary or exercise trained for 10 weeks. Following the exercise or sedentary period, rats were randomly assigned to treatment groups. Rats in sedentary and exercise groups received saline or a combination of 10 mg/kg DOX and 30 mg/kg GW2974. Cardiac function was assessed 2, 5, or 10 days following treatments. RESULTS: Sedentary animals receiving DOX/GW2974 experienced significant cardiac dysfunction. At 2-, 5-, and 10-days post, cardiac function in trained, drug-treated animals was significantly preserved. Additionally, animals exercised prior to DOX/GW2974 injections had significantly lower levels of myocardial lipid peroxidation and caspase-3 and -8 activities compared to their sedentary counterparts. CONCLUSIONS: Exercise training protected against the cardiac dysfunction associated with DOX/GW2974 administration and may be related to an inhibition in apoptotic signaling.

Effects of voluntary wheel running on goserelin acetate-induced bone degeneration.

A common treatment option for many breast and prostate cancer patients is the use of a luteinizing hormone-releasing hormone agonist such as goserelin acetate (GA) which reduces sex hormone levels. This treatment, however, is associated with bone degeneration, and exercise has been suggested as a means of preventing this side effect. Little is known about the effects of low intensity, low volume exercise on GA-induced bone loss. The purpose of this study, therefore, was to investigate the effects of voluntary wheel running on bone architecture in growing male (M) and female (F) rats receiving GA treatment. Rats received an 8-week GA treatment or placebo (CON) and were either housed in cages equipped with voluntary running wheels (WR) or remained sedentary (SED) in standard cages throughout the experimental period. Following treatments, tibiae were excised and analyzed for cortical bone (cross-sectional volume, cortical volume, marrow volume, cortical thickness) and cancellous bone (bone volume/total volume, trabecular number, trabecular thickness, trabecular spacing) using micro-computed tomography. Treatment with GA resulted in a significant reduction in running wheel distances in both sexes throughout the study period (P<0.05). GA treatment had no effect on cortical bone architecture in neither sex (P>0.05). Cancellous bone degeneration, however, was observed in M and F SED+GA (P<0.05). No significant differences were observed in M WR+GA animals in bone volume/total volume, trabecular number and trabecular spacing when compared to M SED+CON (P>0.05). In F WR+GA, trabecular thickness did not differ from that of F SED+CON (P>0.05), and trabecular spacing was found to be significantly lower than F SED+GA (P<0.05). The current report indicates that 8 weeks of GA treatment promotes cancellous bone degeneration, and voluntary wheel running provides no clear osteoprotection in growing male and female rats.

Effects of a supervised exercise intervention on recovery from treatment regimens in breast cancer survivors.

PURPOSE/OBJECTIVES: To investigate the effects of supervised exercise training on cardiopulmonary function and fatigue in cancer survivors undergoing various clinical treatments. DESIGN: Pretest and post-test quasiexperimental. SETTING: Outpatient oncology rehabilitation center. SAMPLE: 96 breast cancer survivors undergoing various clinical treatments. METHODS: Subjects were divided into four groups based on the specific type of clinical treatment: surgery alone (n = 22); surgery and chemotherapy (n = 30); surgery and radiation (n = 17); and surgery, chemotherapy, and radiation (n = 27). Following a comprehensive screening and medical examination, cardiovascular endurance, pulmonary function, and fatigue were assessed, leading to the development of an individualized exercise prescription and a six-month exercise intervention. Repeated-measures analysis of variance and covariance were used to compare the effectiveness of the intervention and differences among treatment groups. MAIN RESEARCH VARIABLES: Systolic and diastolic blood pressure, resting heart rate, forced vital capacity, forced expiratory volume, predicted oxygen consumption, time on treadmill, and fatigue. FINDINGS: Cardiopulmonary function (predicted maximal oxygen consumption and time on treadmill) significantly increased in all groups after exercise training. In addition, resting heart rate and forced vital capacity significantly improved in those receiving surgery, chemotherapy, and radiation. Psychologically, the exercise intervention resulted in significant reductions in behavioral, affective, sensory, cognitive and mood, and total fatigue scale scores in all three groups who received treatment with surgery. The breast cancer survivors in the surgery-alone group showed significant reductions in behavioral, affective, and total fatigue scale scores but not in sensory and cognitive and mood fatigue scale scores. CONCLUSIONS: The results suggest that moderate intensity, individualized, prescriptive exercise maintains or improves cardiopulmonary function with concomitant reductions in fatigue regardless of treatment type. Moreover, cancer survivors receiving combination chemotherapy and radiotherapy following surgery appear to benefit to a greater extent as a result of an individualized exercise intervention. IMPLICATIONS FOR NURSING: Clinicians need to be aware of adjuvant therapies such as moderate exercise that attenuate negative side effects of cancer treatments. Symptom management recommendations should be given to cancer survivors concerning the effectiveness of exercise throughout the cancer continuum and the importance of participating in a cancer rehabilitation exercise program.

Acute exercise protects against doxorubicin cardiotoxicity.

UNLABELLED: Numerous methods have been used to minimize the cardiotoxic effects of the chemotherapeutic agent doxorubicin (DOX), and most have had limited success. Chronic endurance exercise has been shown to protect against DOX cardiotoxicity, but little is known regarding the effects of acute exercise on DOX-induced cardiac dysfunction. PURPOSE: The purpose of this study was to determine the effects of a single bout of acute endurance exercise on the cardiac dysfunction associated with DOX treatment. METHODS: Male Sprague-Dawley rats either performed an acute exercise bout on a motorized treadmill for 60 minutes at a maximal speed of 25 m/min with a 5% grade (EX) or remained sedentary (SED) 24 hours before receiving either a 15-mg/kg DOX bolus dose or saline (SAL). Cardiac function was then analyzed 5 days post injection using a Langendorff isolated perfused heart model. In addition, myocardial lipid peroxidation was analyzed as an indicator of oxidative stress. RESULTS: Doxorubicin treatment alone (SED+DOX) promoted a significant decline in end-systolic pressure (-35%), left ventricular developed pressure (-59%), and the maximal rate of left ventricular pressure development (-43%) as well as a 45% increase in lipid peroxidation products when compared with SED+SAL (P<.05). Acute exercise 24 hours before DOX treatment, however, had a cardioprotective effect, as end-systolic pressure, left ventricular developed pressure, and the maximal rate of left ventricular pressure development were significantly higher in EX+DOX compared with SED+DOX (P<.05) and EX+DOX had similar levels of lipid peroxidation products as SED+SAL CONCLUSIONS: An acute exercise bout performed 24 hours before DOX treatment protected against cardiac dysfunction, and this exercise-induced cardioprotection may partly be explained by a reduction in the generation of reactive oxygen species.

Exercise preconditioning protects against doxorubicin-induced cardiac dysfunction.

UNLABELLED: The clinical use of the chemotherapeutic drug doxorubicin (DOX) is limited due to a dose-dependent cardiotoxicity. Evidence is mounting that exercise protects against DOX-related cardiac dysfunction, and as such, it may be possible that prior endurance training promotes defense against DOX cardiotoxicity. PURPOSE: To examine the effects of exercise preconditioning on acute DOX-induced cardiotoxicity, and to determine whether any observed cardioprotection was associated with myosin heavy chain (MHC) isoform alterations. METHODS: Male Sprague-Dawley rats trained on a motorized treadmill, had access to voluntary running wheels, or remained sedentary for 10 wk prior to being injected with either saline or 10 mg.kg(-1) DOX. Left ventricular function was then assessed in vivo using transthoracic echocardiography and ex vivo using the isolated working heart at 5 and 10 d after injection. Additionally, left ventricular MHC isoform expression was analyzed as a possible mechanism to explain exercise-induced cardioprotection. RESULTS: DOX treatment promoted significant in vivo and ex vivo cardiac dysfunction at 5 and 10 d after injection in sedentary animals, and this dysfunction was associated with an upregulation of the beta-MHC isoform. Exercise preconditioning protected against DOX-induced cardiac dysfunction at 5 and 10 d after injection by attenuating beta-MHC upregulation. CONCLUSION: Endurance training prior to DOX treatment protects against acute DOX cardiotoxicity for up to 10 d, and this protection can potentially be explained by a preservation of MHC isoform distribution.

Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats.

Reducing testosterone and estrogen levels with a luteinizing hormone-releasing hormone agonist such as Zoladex (i.e., chemical gonadectomy) is a common treatment for many prostate and breast cancer patients, respectively. There are reports of surgical gonadectomy inducing cardiac dysfunction, and exercise has been shown to be cardioprotective under these circumstances. Minimal research has been done investigating the effects of chemical gonadectomy and increased physical activity on cardiac function. The purpose of this investigation was to examine the effects of chemical gonadectomy and physical activity on cardiac function. Male (M) and female (F) Sprague-Dawley rats received either Zoladex treatment (Zol) that suppressed gonadal function for 8 wk or control implants (Con) and either were allowed unlimited access to voluntary running wheels (WR) or remained sedentary (Sed) throughout the treatment period. In vivo and ex vivo left ventricle (LV) function were then assessed, and myosin heavy chain (MHC) expression was analyzed to help explain LV functional differences. Hearts from M Sed+Zol exhibited significantly lower aortic blood flow velocity, developed pressure, and maximal rate of pressure development and higher beta-MHC expression than M Sed+Con. Hearts from F Sed+Zol exhibited significantly lower LV wall thicknesses, fractional shortening, and developed pressure and higher beta-MHC expression than F Sed+Con. This cardiac dysfunction was not evident in hearts from M or F WR+Zol, and this was associated with a preservation of the MHC isoform distribution. Thus an 8-wk chemical gonadectomy with Zoladex promoted cardiac dysfunction in male and female rats, and voluntary wheel running protected against this cardiac dysfunction.