Master of Science / Department of Kinesiology / Steven W. Copp / Cancer patients have a reduced exercise capacity compared to age-matched healthy counterparts which contributes to premature fatigue. The reductions in exercise capacity are multifactorial and vary depending on the type of treatments and the specific cancer. Given that cancer treatments have been shown to impair cardiovascular and/or skeletal muscle function, it is difficult to determine if cancer itself reduces exercise capacity. We used a rat prostate tumor model to test the hypothesis that cancer independently reduces endurance exercise capacity. Methods: In male Copenhagen rats (COP/CrCrl), an initial treadmill test to exhaustion was used to determine endurance exercise capacity. Subsequently, the prostates of the rats were injected with either prostate carcinoma cells (R-3327 AT-1) in Matrigel (cancer: n = 9) or Matrigel only (sham: n = 7). Treadmill tests to exhaustion were repeated four and eight weeks post-surgery. Results: Time to exhaustion decreased over the course of the experimental protocol in both the sham and cancer groups. However, the overall reduction in time to exhaustion in the cancer group (-16.7 ± 1.9 min) was significantly greater (p = 0.038) than the sham group (-10.1 ± 2.2 min). Despite no differences in total body mass at the end of the experimental protocol, heart, left ventricle, and gastrocnemius muscle mass were significantly lower in the cancer group compared to the sham group (p < 0.05 for all). Moreover, within the cancer group heart and left ventricle mass, but not gastrocnemius mass, were significantly inversely correlated with prostate tumor mass. Conclusion: Endurance exercise capacity was reduced in rats with untreated prostate cancer to a greater extent than it was reduced in sham operated rats. Although multiple mechanisms likely contributed to the reduced exercise capacity, reductions in heart and gastrocnemius muscle mass likely played an important role.

No description available.

Hypertensive patients exhibit impaired exercise capacity, a strong independent risk factor for cardiovascular disease, and the mechanisms responsible for this are not fully determined. Potential candidates may include endothelial vasomotor dysfunction and arterial stiffness, both of which are associated with hypertension. Impairment of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a major role in the development of these abnormalities, suggesting that enhancement of NO-cGMP signalling through phosphodiesterase type 5 (PDE5) inhibition may offer therapeutic potential in arterial hypertension. This thesis investigated the effects of the PDE5 inhibitor sildenafil citrate on exercise-induced vasodilatation, maximal exercise capacity and arterial stiffness in hypertensive patients, using different studies involving local limb and whole body exercise. Preliminary dose-ranging studies were initially performed to investigate the intraarterial (brachial) effects of sildenafil on forearm blood flow (FBF), and to select an appropriate, cGMP-independent, vasodilator to use as a control. On the basis on these studies, it was established that sildenafil, infused at 50μg/min, and verapamil, infused at 5μg/min, had similar vasodilator effect on FBF. Ten untreated hypertensive patients and ten matched normotensive subjects were then studied in a three-way, randomised, single-blind and placebo-controlled FBF study. The aim was to investigate the effects of sildenafil on handgrip exercise-induced vasodilatation, and to compare this response with verapamil and saline (placebo). Preinfusion exercise-induced vasodilatation was significantly reduced in hypertensive compared with normotensive subjects (P<0.001). However, after the infusions, while verapamil did not affect the vasodilator response to exercise in either group, sildenafil substantially enhanced this response in hypertensive patients, but not in normotensive subjects (P<0.05). These results suggested that sildenafil, through an increase in cGMP levels in the vasculature, substantially and selectively improves the vasodilator response to handgrip exercise in hypertensive patients.

With a growing ageing population decline in physical function has become a major public health issue, as it is associated with disability in later life. Recent evidence suggests that blockade of the renin-angiotension-aldosterone system may have a role in improving physical function in older people.We hypothesised that inhibition of the renin-angiotensin-aldosterone system with spironolactone would improve physical function in older people without heart failure. In a double-blind, randomised controlled clinical trial 120 participants, aged &gt;65 years with functional impairment were randomized to receive 25mg spironolactone or placebo for 20 weeks. The primary outcome was the change in six-minute walking distance over 20 weeks. Secondary outcomes were change in Timed-Get-Up and Go test, Incremental Shuttle Walk Test, measures of health related quality of life (EuroQol health questionnaire and Functional Limitation Profile) and measures of psychological state (Hospital Anxiety and Depression Scale). Outcomes measures were repeated at 10 and 20 weeks.Participant mean age was 75 years (SD 6), 65/120 (54%) were male. Only 8/120 participants (6.6%) dropped out (5 from the placebo group, 3 from the spironolactone group). Of the 112 participants who completed the study 95% (106/112) remained on medication at 20 weeks. There was no significant change in six minute walking distance at 20 weeks with a -3.2 (95% CI -28.9, 22.5) metres difference between the spironolactone group related to the placebo group (p=0.81). There was however a significant improvement in quality of life at 20 weeks (a secondary outcome) with a rise in EuroQol EQ-5D score of 0.10 (95% CI 0.03, 0.18) in the spironolactone group relative to the placebo group (p=&lt;0.01). There were no significant changes between groups in the other secondary outcomes. This trial found that spironolactone was safe and well tolerated, but did not improve physical function in older people who did not have heart failure. Quality of life improved, but the biological plausibility and possible mechanisms for this require further study.

ABSTRACT The Benefits of Yoga Therapy for Heart Failure Patients by Paula R. Pullen STATEMENT OF THE PROBLEM The number of patients living with heart failure (HF) is on the rise. Yoga has been found to improve physical and psychological parameters amongst healthy individuals. The effects of yoga on HF patients are unknown. The purpose of this study was to examine the effects of yoga on cardio-vascular endurance [functional capacity (FC)], flexibility, inflammatory markers, and quality of life (QoL) on medically stable HF patients. METHOD Forty HF patients with compensated systolic or diastolic HF participated in the study. A randomized control design created two groups, yoga (N=21). and control (N=19).The treatment intervention consisted of 16-yoga sessions conducted bi-weekly (YG) vs. standard medical care (control- CG) for two months. All participants were asked to follow a home walk program. Pre- and post-study measurements included a treadmill stress test to peak exertion, flexibility (FLEX), girth, interleukin-6 (IL-6), c- reactive protein (CRP), and extra-cellular dismutase (EC-SOD). Quality of life was assessed by the Minnesota Living with Heart Failure Questionnaire (MLwHFQ). RESULTS Forty patients were randomized to YG (N=21) or CG (N=19). The results were significant for favorable changes in the YG as compared to the CG for flexibility (P=0.012), treadmill time (P=0.002), ~VO2peak (P=0.003), and all biomarkers (IL-6, CRP, and EC-SOD) of inflammation. Within the YG, pre- to post- test scores for the total and physical sub- scale of the MLwHFQ were significant (P=0.02 and P<0.001). CONCLUSIONS Yoga therapy offered additional benefits to the standard medical care of HF patients by improving QoL, exercise capacity, FLEX, and biomarkers of inflammation

No description available.

It is known that during fluid restriction, obligatory water losses continue and hypohydration develops and that restricted energy intake leads to a concomitant restriction of all other dietary components, as well as hypohydration, but the specific effects of periods of fluid and/ or energy restriction on fluid balance, electrolyte balance and exercise performance have not been systematically described in the scientific literature. There were two main aims of this thesis. Firstly, to describe the effects of periods of severe fluid and/ or energy restriction on fluid and electrolyte balance; secondly, to determine the effect of electrolyte supplementation during and after energy restriction on fluid and electrolyte balance as well as energy exercise performance. The severe restriction of fluid and/ or energy intake over a 24 h period all resulted in body mass loss (BML) and hypohydration, but whilst serum osmolality increases during fluid restriction (hypertonic hypohydration), serum osmolality does not change during energy restriction (isotonic hypohydration), despite similar reductions in plasma volume (Chapter 3). These differences in the tonicity of the hypohydration developed are most likely explainable by differences in electrolyte balance, with fluid restriction resulting in no change in electrolyte balance over 24 h (Chapter 3) and energy restriction (with or without fluid restriction) producing significant reductions in electrolyte balance by 24 h (Chapter 3; Chapter 4; Chapter 5; Chapter 6; Chapter 7). Twenty four hour combined fluid and energy restriction results in large negative balances of both sodium and potassium, and whilst the addition of sodium chloride to a rehydration solution ingested after fluid and energy restriction increases drink retention, the addition of potassium chloride to a rehydration solution does not (Chapter 4). Supplementation of sodium chloride and potassium chloride during periods of severe energy restriction reduces the BML observed during energy restriction and maintains plasma volume at pre-energy restriction levels (Chapter 5; Chapter 6; Chapter 7). iv These responses to electrolyte supplementation during energy restriction appear to be related to better maintenance of serum osmolality and electrolyte concentrations and a consequential reduction in urine output (Chapter 5; Chapter 6; Chapter 7). Additionally, 48 h energy restriction resulted in a reduction in exercise capacity in a hot environment and an increase in heart rate and core temperature during exercise, compared to a control trial providing adequate energy intake. Whilst electrolyte supplementation during the same 48 h period of energy restriction prevented these increases in heart rate and core temperature and exercise capacity was not different from the control trial Chapter 8). In conclusion, 24-48 h energy restriction results in large losses of sodium, potassium and chloride in urine and a large reduction in body mass and plasma volume and supplementation of these electrolytes during energy restriction reduces urine output, attenuates the reduction in body mass and maintains plasma volume and exercise capacity.

Background: Exercise capacity (EC) is widely recognized as a strong and independent predictor of mortality and disease progression in various diseases, including cardiovascular and pulmonary diseases. Furthermore, it is generally accepted that exercise capacity in healthy individuals and in patients suffering from cardiovascular diseases is mainly limited by the maximum cardiac output. Objectives: This thesis investigated the impact of different lung function indices on EC in healthy individuals, patients with cardiovascular disease (e.g., pulmonary hypertension (PH)) and patients with pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD)). Methods: The present thesis is based on cross-sectional and longitudinal analyses of patients suffering from COPD, attending pulmonary rehabilitation at Uppsala University Hospital (studies I and II), and healthy men enrolled in the “Oslo ischemia study” (study IV). Study III is a cross-sectional study of patients suffering from PH attending the San Giovanni Battista University Hospital in Turin. EC was assessed using a bicycle ergometer in studies I and IV, with 12-minute walk tests (12MWT) in study II and with 6-minute walk tests (6MWT) in study III. Extensive pulmonary function tests, including diffusing capacity of the lung (DLCO), were performed in studies I-III and dynamic spirometry was used to assess lung function in study IV. Results: DLCO is more closely linked to decreased levels of EC than airway obstruction in COPD patients. Furthermore, the decline in 12MWT over a 5-year period was mainly explained by deterioration in DLCO in COPD patients. Spirometric parameters indicating airway obstruction significantly related to EC and exercise-induced desaturation in PH patients. A significant, but weak association between lung function parameters and EC was found in healthy subjects and this association is strengthened with increasing age. Conclusion: DLCO is the strongest predictor of low EC and EC decline in COPD. In PH, airway obstruction is strongly related to reduced 6MWT. Therefore, extensive analysis of lung function, including measurements of diffusing capacity, along with standard assessment of airway obstruction, gives a more comprehensive assessment of the functional exercise capacity in patients suffering from pulmonary hypertension or COPD. Lung function is also significantly linked to EC even in healthy subjects, lacking evident cardiopulmonary diseases.

The purpose of this study was to evaluate graded exercise responses to treadmill exercise in patients with a total artificial heat (SynCardia, Tucson, AZ). Additionally, this study sought to compare the exercise response in total artificial heart (TAH) patients to both advanced heart failure (HF) patients on medical management only and HeartMate II (Thoratec Corp., Pleasanton, CA) left‐ventricular assist device (HMII) patients. For patients with biventricular heart failure the TAH is a viable option to bridge patients until transplant becomes available. Its demonstrated improvement in mortality and increasing usage necessitates a shift in focus to quality of life in the TAH patient including functional ability. The evaluation of cardiorespiratory responses to graded exercise provides an objective measure of functional ability. There is very limited information in the literature on the exercise response of the mechanical circulatory support (MCS) device patient, particularly the TAH patient. A review was performed on MCS patients who underwent symptom‐limited cardiopulmonary exercise testing (CPET) following device implant of either TAH or HMII. ANOVA was performed to compare differences between the two device groups and HF patients listed for heart transplant. Fourteen TAH patients underwent CPET (9 male, 5 female) with peak oxygen consumption (VȩO2) of 0.926 + .168 L∙min, 36 + 8% % predicted, 11.0 + 2.3 ml.kg.min or 3.1 + 0.7 METs. Ventilatory anaerobic threshold (VAT) was 0.706 + .181 L∙min. Peak (VȩO2, % pred. (VȩO2 and VAT were significantly lower in the TAH compared with HMII and advanced HF (p = 0.0012, p = 0.0106, p = 0.0009, respectively). Peak RER was significantly higher (p = <.0001) and OUES was significantly lower (p = 0.0004) in the TAH. Exercise capacity is significantly reduced in the TAH patient below that observed in HMII LVAD and advanced HF patients. This provides a baseline for expected functional status and has implications on the ADL tolerance of these individuals. The next step is to develop strategies to ameliorate this continued exercise intolerance. The documents herein contain a review of literature including a background in heart failure and the use of the exercise response in the heart failure patient. An overview is also presented on the use of MCS describing physiology, device function, and exercise physiology of the MCS device patient. A manuscript has also been included detailing a cross‐sectional review of the effects of graded exercise in the TAH patient and comparing it to the HMII and advanced HF patient.

Little is known about the early recovery of functional outcomes in the lung transplant population. This thesis investigated skeletal muscle strength, functional exercise capacity, health-related quality of life and daily physical activity pre- and early post-lung transplantation in a cohort of fifty participants. Significant functional limitations were observed pre-transplant, however levels of physical activity were higher on rehabilitation days as compared to non-rehabilitation days. Post-transplant, improvements in functional exercise capacity and physical activity lagged behind the early improvements in pulmonary function and health-related quality of life. Muscle strength was reduced at hospital discharge compared to pre-transplant levels, but improved to pre-transplant levels by three months post-transplant. In summary, significant functional limitation exists pre-transplant, and lung transplantation leads to significant improvement of functional outcomes; however functional recovery occurs at different time periods and to varying degrees, and does not reach levels of a healthy reference population by three months post-lung transplant.