Research Publications and Abstracts

Recent Publications

Wonders KY, Hydock DS, Schneider CM, Hayward R. Acute Exercise Protects Against Doxorubicin Cardiotoxicity. Integrative Cancer Therapies 7: 147-154, 2008.

Hydock DS, Lien C-Y, Schneider CM, Hayward R.  Exercise Preconditioning Protects Against Doxorubicin-Induced Cardiac Dysfunction. Medicine and Science in Sports and Exercise 40: 808-817, 2008.

Hydock DS, Lien C-Y, Schneider CM, Hayward R.  Effects of Voluntary Wheel Running on Cardiac Function and Myosin Heavy Chain in Chemically Gonadectomized Rats. American Journal of Physiology: Heart and Circulatory Physiology 293: H3254-H3264, 2007.

Schneider CM, Hsieh CC, Sprod LK, Carter SD, Hayward R. Cancer Treatment-Induced Alterations in Muscular Fitness and Quality of Life: The Role of Exercise Training. Annals of Oncology 18: 1957-1962, 2007.

Wonders KY, Hydock DS, Hayward R. Time-course of Changes in Cardiac Function During Recovery After Acute Exercise.  Applied Physiology, Nutrition, and Metabolism 32: 1164-1169, 2007.

Hayward R, Hydock DS. Doxorubicin Cardiotoxicity in the Rat: An In Vivo Characterization.  Journal of the American Association for Laboratory Animal Science 46: 20-32, 2007.

Schneider CM, Hsieh CC, Sprod LK, Carter SD, Hayward R. The Effects of Supervised Exercise Training on Cardiopulmonary Function and Fatigue in Breast Cancer Survivors During and Following Treatment. Cancer 110 918-25, 2007.

Schneider CM, Hsieh CC, Sprod LK, Carter SD, Hayward R. Exercise Training Manages Cardiopulmonary Function and Fatigue During and Following Cancer Treatment in Male Cancer Survivors. Integrative Cancer Therapies 6: 235-41, 2007.

Hydock DS, Wonders KY, Schneider CM, Hayward R. Androgen Deprivation Therapy and Cardiac Function: Effects of Endurance Training.  Prostate Cancer and Prostatic Disease 9: 392-398, 2006.

Recent Abstracts

Three Versus Six Months of Exercise Training in Breast Cancer Survivors
Sprod, Lisa K.1; Hsieh, City C.2; Carter, Susan D.1; Hayward, Reid1; Schneider, Carole M. FACSM1
1Rocky Mtn Cancer Rehab, Univ Northern Colorado, Greeley, CO. 2National HsinChu University of Education, HsinChu, Taiwan.
Breast cancer is the most prevalent type of cancer affecting women. Fortunately, the incidence of breast cancer development has stabilized and the overall survival rate has been increasing. Breast cancer and the treatments used to ameliorate the cancerous cells have serious physiological and psychological deleterious side-effects. Exercise appears to diminish many of these side-effects. However, minimal research has been completed comparing the outcomes of varying lengths of exercise interventions on physiological and psychological parameters.
PURPOSE: To compare the physiological and psychological alterations that occur as a result of three and six months of individualized exercise interventions in breast cancer survivors.
METHODS: One-hundred and fourteen breast cancer survivors participated. Twenty-nine of the participants underwent three months of prescriptive, individualized exercise, 68 underwent six months of prescriptive, individualized exercise and 17 served as sedentary controls. Participants completed a medical evaluation and assessment at baseline followed by a predetermined three or six month exercise intervention. Participants in the sedentary control group performed no exercise between the initial assessment and six month reassessment. Cardiovascular endurance, pulmonary function, fatigue, and depression were assessed at baseline and following the intervention.
RESULTS: Repeated measures ANCOVA revealed improvements (p<.05) in cardiovascular endurance, fatigue, and depression in breast cancer survivors undergoing three and six month individualized exercise interventions. Breast cancer survivors exercising for six months showed additional improvements (p<.05) in pulmonary function. Participants in the control group did not show improvements in cardiovascular endurance, pulmonary function, or fatigue.
CONCLUSION: Cancer treatments can result in severe physiological and psychological impairment. Results of this investigation attest to the value of individualized, prescriptive exercise for breast cancer survivors lasting as little as three months in duration for improving cardiovascular endurance, fatigue, and depression. Additional benefits are seen if exercise is continued for greater lengths of time and ideally across the lifespan.

Health-Related Fitness and Quality of Life in Cancer Survivors
Repka, Chris P.1; Sprod, Lisa K.1; Hsieh, City C.2; Hydock, David S.1; Carter, Susan D.1; Hayward, Reid1; Schneider, Carole M. FACSM1
1Rocky Mtn Cancer Rehab, Univ Northern Colorado, Greeley, CO. 2National HsinChu University of Education, HsinChu, Taiwan.
Advances in the overall effectiveness of cancer treatments have significantly increased cancer survival rates. However, these therapies have severe negative side effects lasting for days, months or even years following treatment. Therefore, it has become essential to determine strategies that will enhance the quality of life of cancer survivors.
PURPOSE: Determine the effects of exercise on health-related fitness and quality of life (QOL) in cancer survivors during and following cancer treatment utilizing similar exercise assessments and individualized exercise interventions.
METHODS: Two hundred seven cancer survivors were grouped according to cancer treatment status. Thirty-one survivors were undergoing treatment (DTm) while one hundred seventy-six had completed treatment (FTm). Following a medical examination, body composition, cardiovascular endurance, muscular strength and endurance, flexibility, depression, QOL and fatigue were assessed for the development of an individualized 6-month exercise intervention. Repeated-measures analysis of variance (ANOVA) and analyses of covariance (ANCOVA) were used to compare the effectiveness of the intervention and differences between groups.
RESULTS: Cardiovascular endurance [predicted maximal oxygen consumption, time on treadmill] improved (p<.05) in the DTm and FTm groups. Muscular endurance [bench press, lats pulldown, shoulder press, leg press, leg extension, leg curl, curl crunches] improved (p<.05) in the FTm group while the DTm group maintained muscular endurance in the upper and lower body and improved (p<.05) on abdominal muscular endurance. Flexibility (sit & reach) improved (p<.05) in both groups. Psychologically, depression improved (p<.05) in the DTm and FTm groups while total QOL and total fatigue were maintained in the DTm group and improved (p<.05) in the FTm group. Body composition was maintained in both groups while handgrip strength was maintained in the FTm group and decreased (p<.05) in the DTm group.
CONCLUSION: Moderate intensity, individualized prescriptive exercise improved or maintained health-related fitness and QOL in cancer survivors during and following cancer treatment. Thus, an appropriately implemented exercise intervention is a possible strategy to attenuate the side effects of cancer treatments.

Effects of Goserelin Acetate and Voluntary Wheel Running on Bone Morphology in Female Rats
Parry, Traci1; Hydock, David S.1; Iwaniec, Urszula T.2; Turner, Russell T.2; Lien, Chia-Ying1; Jensen, Brock T.1; Hayward, Reid1
1University of Northern Colorado, Greeley, CO. 2Oregon State University, Corvallis, OR.
The luteinizing hormone-releasing hormone (LHRH) agonist, goserelin acetate, is used in the clinical setting to treat hormone-sensitive cancers in pre- and perimenopausal women. With prolonged use, this treatment has been shown to decrease bone mineral density due to a reduction in estrogen release by the ovaries. Regular physical activity, in contrast, has been shown to provide a number of beneficial effects on bone health.
PURPOSE: To determine whether voluntary wheel running attenuates the negative effects of goserelin acetate on proximal and diaphyseal tibial bone structure in female rats.
METHODS: Female Sprague-Dawley rats (n=40) were randomly assigned to one of four groups: sedentary control, SED+C; sedentary goserelin acetate, SED+GA; voluntary wheel run control, WR+C; and voluntary wheel run goserelin acetate, WR+GA. Animals treated with GA received implants on day 1 and 29 while control animals received sham implants. During the 56 day experimental protocol, SED animals did not exercise while animals in WR groups were allowed free access to cage-mounted running wheels. Upon completion of the 56 day drug and exercise regimens, animals were sacrificed and the tibia was excised and assessed for bone architecture via Micro Computed Tomography.
RESULTS: Treatment with GA had no effect on tibial diaphyseal total bone volume, cortical volume, cortical volume/total volume ratio, marrow volume, or cortical thickness. GA treatment did, however, significantly lower bone volume (-79%, p < 0.001), bone volume/total volume ratio (-78%, p < 0.001), trabecular number (-62%, p < 0.001), trabecular thickness (-8%, p < 0.05), and significantly increased trabecular spacing (+182%, p < 0.001). Voluntary wheel running did not protect against the degenerative tibial bone effects of GA on bone volume, bone volume/total volume ratio, or trabecular thickness. Voluntary running attenuated the decline in trabecular spacing and trabecular number (p<0.05), yet even with this attenuation, trabecular spacing was still 50% lower than SED+C and trabecular number was still 115% higher than SED+C.
CONCLUSION: Goserelin acetate had a degenerative effect on cancellous bone while demonstrating little effect on cortical bone. Voluntary wheel running provided minimal benefits on bone morphology in female rats during GA treatment.


Effects of Short-Term Exercise on Doxorubicin-Induced Cardiotoxicity
Jensen, Brock T.; Hydock, David S.; Lien, Chia-Ying; Schneider, Carole M. FACSM; Hayward, Reid
University of Northern Colorado, Greeley, CO.
Numerous methods have been employed to minimize the cardiotoxic effects of the chemotherapeutic agent doxorubicin (DOX), and most have had minimal success. Chronic endurance exercise, however, has previously been shown to protect against DOX cardiotoxicity, but very little is known regarding the effects of short-term exercise on DOX-induced cardiac dysfunction.
PURPOSE: To investigate the effects of short-term voluntary running activity performed 1, 3, or 5 days prior to DOX administration, on cardiac function.
METHODS: Female Sprague-Dawley rats (n=80) were randomly assigned to 1 of 2 primary experimental groups: sedentary (SED) or voluntary wheel running (VOL). Animals in VOL groups were housed in cages equipped with a commercially available running wheel for 1 (1VOL), 3 (3VOL), or 5 (5VOL) days. Following the activity period, animals in each group were randomly assigned to receive either 10 mg·kg-1 DOX (1VOL+DOX, 3VOL+DOX, 5VOL+DOX, SED+DOX) or saline (1VOL+SAL, 3VOL+SAL, 5VOL+SAL, SED+SAL). Left ventricle function was assessed ex vivo using an isolated working heart model 5 days post DOX exposure.
RESULTS: Doxorubicin treatment alone (SED+DOX) promoted a significant decline in left ventricular developed pressure (LVDP, -17%), and the maximal rate of left ventricular development (dP/dtmax, -13%) when compared to SED+SAL (p<0.05). Short-term voluntary exercise 1, 3, and 5 d prior to DOX treatment, however, had a cardioprotective effect as, LVDP and dP/dtmax, were not significantly lower in 1VOL+DOX, 3VOL+DOX, and 5VOL+DOX when compared to SED+SAL (p>0.05).
CONCLUSIONS: Short-term voluntary running activity performed either 1, 3, or 5 days prior to DOX treatment protects against DOX-induced cardiac dysfunction.

Late Onset Doxorubicin-Induced Cardiac Dysfunction is Attenuated in Exercise Preconditioned Rats
Hydock, David S.; Lien, Chia-Ying; Jensen, Brock T.; Schneider, Carole M. FACSM; Hayward, Reid
University of Northern Colorado, Greeley, CO.
Previously we reported that early onset (i.e., acute) doxorubicin (DOX) cardiotoxicity (5 and 10 days post-treatment) was attenuated in previously treadmill trained and voluntary wheel run rats. Little is known, however, whether this exercise preconditioning-induced cardioprotection continues beyond 10 days post-DOX administration.
PURPOSE: To determine the effects of prior treadmill training and voluntary wheel running on late onset DOX-induced cardiac dysfunction.
METHODS: Male Sprague-Dawley rats were randomly assigned to either treadmill (TM), wheel running (WR), or sedentary (SED) groups. TM and WR animals participated in a progressive treadmill training protocol or voluntary wheel running, respectively, for 10 weeks. Following the activity intervention, animals were further randomized to receive either a 10 mg/kg cumulative dose of DOX (TM+DOX, WR+DOX, SED+DOX) or saline (TM+SAL, WR+SAL, SED+SAL). All animals then remained sedentary for 4 weeks. Following the sedentary period, left ventricle (LV) function was assessed in vivo using transthoracic echocardiography and ex vivo using an isolated working heart model.
RESULTS: A 22% reduction in fractional shortening was observed in LVs from previously sedentary animals receiving DOX when compared to SED+SAL (p<0.05). This degree of decline, however, was not observed in TM+DOX (-12%, p>0.05) and WR+DOX (-14%, p>0.05) when compared to SED+SAL. Likewise, SED+DOX possessed significantly depressed mitral valve maximal blood flow velocity (-37%, p<0.001) and aortic valve maximal blood flow velocity (-48%, p<0.001) when compared to SED+SAL, but these decrements were not observed in TM+DOX and WR+DOX (p>0.05 vs. SED+SAL). Ex vivo analysis revealed that LV developed pressure and maximal rate of pressure development were significantly lower in SED+DOX when compared to SED+SAL (-21%, p<0.001 and -17%, p<0.05, respectively). Treadmill training and wheel running prior to DOX treatment, however, protected against these decrements (p>0.05 vs. SED+SAL).
CONCLUSION: Ten weeks of treadmill and voluntary wheel run preconditioning protected against late onset DOX-induced cardiac dysfunction suggesting that training status may help determine the degree of late onset cardiotoxicity in cancer patients undergoing treatment with DOX.

Low-Intensity, Low-Frequency Exercise Protects Against DOX-Induced Cardiac Dysfunction in Rats
Lien, Chia-Ying; Hydock, David S.; Jensen, Brock T.; Schneider, Carole M. FACSM; Hayward, Reid
University of Northern Colorado, Greeley, CO.
A common chemotherapeutic agent, doxorubicin (DOX), is associated with dose-dependent cardiotoxicity. Some evidence suggests that endurance training prior to DOX administration protects against DOX-induced cardiac dysfunction. However, the effects of exercise training on cardiac function during and after DOX treatment are not clear.
PURPOSE: To investigate whether low-intensity exercise training during and after DOX treatment can minimize cardiotoxicity.
METHODS: Male Sprague-Dawley rats (~300g, n=62) were randomly assigned to one of two primary experimental groups: DOX-treated (DOX, n= 32) and saline-treated (SAL, n=30). DOX treatment consisted of 5 weekly injections of DOX at 2 mg/kg for a total cumulative dose of 10 mg/kg. SAL animals received an equivalent volume of saline. Rats were then further subdivided into sedentary (SED+SAL, SED+DOX), 5-week exercise (TM5+SAL, TM5+DOX) and 8 week exercise groups (TM8+SAL, TM8+DOX). TM5 animals began treadmill training when SAL/DOX injections began, stopped training when injections were completed, and remained sedentary for 3 weeks. TM8 animals began treadmill training when SAL/DOX injections began and continued training for 3 weeks after injections were completed. SED animals remained in their cages for the duration of the study. Animals in TM groups exercised on a motorized rodent treadmill (16 m/min, 3 days/week, 30 min/day) for either 5 (TM5) or 8 (TM8) weeks. Following the 8-week observation period, left ventricular (LV) function was measured using an isolated working heart model.
RESULTS: LV developed pressure (SED+SAL 115.2±3.3 mmHg vs. SED+DOX 92.5±3.8 mmHg, p<0.01) and the maximal rate of LV pressure development (SED+SAL 4785±159 mmHg/s vs. SED+DOX 3947±143 mmHg/s, p<0.01) were compromised by DOX treatment. However, LV developed pressure and the maximal rate of LV pressure development in TM5+DOX and TM8+DOX hearts was not significantly different than SED+SAL. Interestingly, we observed no statistical differences between TM5+DOX and TM8+DOX cardiac function.
CONCLUSION: Low-intensity, low-frequency exercise training protected against DOX cardiotoxicity. In addition, there appeared no additive benefits of exercising during and after DOX treatment when compared to exercising only during DOX treatment.

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