Exercise increases caudate dopamine release and ventral striatal activation in Parkinson's disease.

BACKGROUND: The objective of this study was to examine the effects of aerobic exercise on evoked dopamine release and activity of the ventral striatum using positron emission tomography and functional magnetic resonance imaging in Parkinson's disease (PD). METHODS: Thirty-five participants were randomly allocated to a 36-session aerobic exercise or control intervention. Each participant underwent an functional magnetic resonance imaging scan while playing a reward task before and after the intervention to determine the effect of exercise on the activity of the ventral striatum in anticipation of reward. A subset of participants (n = 25) completed [11 C] raclopride positron emission tomography scans to determine the effect of aerobic exercise on repetitive transcranial magnetic stimulation-evoked release of endogenous dopamine in the dorsal striatum. All participants completed motor (MDS-UPDRS part III, finger tapping, Timed-up-and-go) and nonmotor assessments (Starkstein Apathy Scale, Beck Depression Inventory, reaction time, Positive and Negative Affect Schedule, Trail Making Test [A and B], and Montreal Cognitive Assessment) before and after the interventions. RESULTS: The aerobic group exhibited increased activity in the ventral striatum during functional magnetic resonance imaging in anticipation of 75% probability of reward (P = 0.01). The aerobic group also demonstrated increased repetitive transcranial magnetic stimulation-evoked dopamine release in the caudate nucleus (P = 0.04) and increased baseline nondisplaceable binding potential in the posterior putamen of the less affected repetitive transcranial magnetic stimulation-stimulated hemisphere measured by position emission tomography (P = 0.03). CONCLUSIONS: Aerobic exercise alters the responsivity of the ventral striatum, likely related to changes to the mesolimbic dopaminergic pathway, and increases evoked dopamine release in the caudate nucleus. This suggests that the therapeutic benefits of exercise are in part related to corticostriatal plasticity and enhanced dopamine release. © 2019 International Parkinson and Movement Disorder Society.

Maintenance of Fitness and Quality-of-Life Benefits From Supervised Exercise Offered as Supportive Care for Breast Cancer.

BACKGROUND: Overwhelming randomized controlled trial evidence demonstrates that exercise has positive health impacts during and after treatment for breast cancer. Yet, evidence generated by studies in which exercise programs are delivered outside a tightly controlled randomized trial setting is limited. The purpose of this study was to assess the effectiveness of an evidence-based exercise program with real-world implementation on physical fitness and quality of life (QoL). PATIENTS AND METHODS: Oncologists referred women with early-stage breast cancer who were scheduled to receive adjuvant chemotherapy. The program consisted of supervised aerobic and resistance exercise of moderate to vigorous intensity 3 times per week until the end of treatment (chemotherapy ± radiotherapy), then twice per week for 10 weeks, followed by once per week for 10 weeks. Health-related physical fitness and QoL were assessed at baseline, end of treatment, end of program, and 1-year follow-up. RESULTS: A total of 73 women were enrolled. Estimated peak VO2 (VO2peak), QoL, and body weight were maintained between baseline and end of treatment, whereas muscular strength improved (P<.01). By the end of the program, VO2peak, heart rate recovery, waist circumference, and some aspects of QoL were improved (all P<.01) relative to baseline. One year later, VO2peak, QoL, and waist circumference were maintained relative to end of program, whereas the improvements in strength and heart rate recovery had dissipated (all P<.01). CONCLUSIONS: Evidence-based exercise programming delivered with real-world implementation maintained VO2peak, strength, and QoL during adjuvant treatment and improved these measures after treatment completion among women with breast cancer. Continued guidance and support may be required for long-term maintenance of strength improvements in this population.

The effect of an aerobic exercise bout 24 h prior to each doxorubicin treatment for breast cancer on markers of cardiotoxicity and treatment symptoms: a RCT.

PURPOSE: In rodents, a single exercise bout performed 24 h prior to a single doxorubicin treatment provides cardio-protection. This study investigated whether performing this intervention prior to every doxorubicin treatment for breast cancer reduced subclinical cardiotoxicity and treatment symptoms. METHODS: Twenty-four women with early stage breast cancer were randomly assigned to perform a 30-min, vigorous-intensity treadmill bout 24 h prior to each of four doxorubicin-containing chemotherapy treatments or to usual care. Established echocardiographic and circulating biomarkers of subclinical cardiotoxicity, as well as blood pressure and body weight were measured before the first and 7-14 days after the last treatment. The Rotterdam symptom checklist was used to assess patient-reported symptoms. RESULTS: The exercise and usual care groups did not differ in the doxorubicin-related change in longitudinal strain, twist, or cardiac troponin. However, the four total exercise bouts prevented changes in hemodynamics (increased cardiac output, resting heart rate, decreased systemic vascular resistance, p < 0.01) and reduced body weight gain, prevalence of depressed mood, sore muscles, and low back pain after the last treatment (p < 0.05) relative to the usual care group. No adverse events occurred. CONCLUSIONS: An exercise bout performed 24 h prior to every doxorubicin treatment did not have an effect on markers of subclinical cardiotoxicity, but had a positive systemic effect on hemodynamics, musculoskeletal symptoms, mood, and body weight in women with breast cancer. A single exercise bout prior to chemotherapy treatments may be a simple clinical modality to reduce symptoms and weight gain among women with breast cancer.

Upper extremity lymphatic function at rest and during exercise in breast cancer survivors with and without lymphedema compared with healthy controls.

Lymphoscintigraphy was used to measure lymphatic function at rest and during exercise in breast cancer survivors with lymphedema (BCRL, n = 10), breast cancer survivors (BC, n = 10), and controls (Cont, n = 10). After injection of (99m)Tc-antimony colloid to the hands, subjects rested or performed 12 repeated sets of arm cranking for 2.5 min at 0.6 W/kg followed by 2.5 min of rest. One-minute spot views were taken with a gamma-radiation camera immediately postinjection and every 10 min over 60 min to calculate clearance rate. As well, an upper body scan was taken at 65 min postinjection to measure radiopharmaceutical uptake in the axilla (Ax) and forearm (Fore). All groups displayed similar increases in clearance rate with exercise (P = 0.000). Ax significantly increased with exercise in Cont only [Cont: (mean +/- SD) 4.9 +/- 2.6 vs. 7.9 +/- 4.2%, P = 0.000; BCRL: 1.4 +/- 1.2 vs. 1.7 +/- 2.1%, P = 0.531; BC: 3.9 +/- 3.4 vs. 5.2 +/- 3.2%, P = 0.130], whereas Fore, indicating dermal backflow, significantly increased in BCRL only (BCRL: 2.4 +/- 0.87 vs. 4.4 +/- 2.0%, P = 0.004; BC: 1.1 +/- 0.25 vs. 1.1 +/- 0.31%, P = 0.784; Cont: 0.93 +/- 0.26 vs. 1.0 +/- 0.20%, P = 0.296). The results indicate that, in women with BCRL, exercise causes radiopharmaceuticals to clear from the hand at the same rate as BC and Cont, but, instead of reaching the axilla, a greater amount of activity gets trapped in the dermis of the forearm. BC, meanwhile, have similar lymphatic function as Cont; however, there is a highly variable response that may suggest that some BC subjects may be at risk for developing lymphedema.

Sex differences in left ventricular function and beta-receptor responsiveness following prolonged strenuous exercise.

Sex differences in neuroendocrine and metabolic responses to prolonged strenuous exercise (PSE) have been well documented. The aim of this investigation was to examine sex differences in left ventricular function and cardiac beta-receptor responsiveness following a single bout of PSE. Nine male and eight female triathletes were examined during three separate sessions: before, immediately after, and 24 h following a half-ironman triathlon using dobutamine stress echocardiography. Steady-state graded infusions of dobutamine were used to assess beta-receptor responsiveness. Slopes calculated from linear regressions between dobutamine doses and changes in heart rate and contractility for each participant were used as an index of beta-receptor responsiveness. Despite no change in preload, fractional area change decreased from baseline after the race in both men and women, with a greater decrease in men [men: 54.1% (SD 2.1) to 50.7% (SD 3.4) vs. women: 55.4% (SD 2.7) to 53.3% (SD 2.5); P < 0.05]. The amount of dobutamine necessary to increase heart rate by 25 beats/min [men: 29.6 microg x kg(-1) x min(-1) (SD 6.6) to 42.7 microg x kg(-1) x min(-1) (SD 12.9) vs. women: 23.5 microg x kg(-1) x min(-1) (SD 4.0) to 30.0 microg x kg(-1) x min(-1) (SD 7.8); P < 0.05] and contractility by 10 mmHg/cm2 [men: 20.9 microg x kg(-1) x min(-1) (SD 5.1) to 37.0 microg x kg(-1) x min(-1) (SD 11.5) vs. women: 22.6 microg x kg(-1) x min(-1) (SD 6.4) to 30.7 microg x kg(-1) x min(-1) (SD 7.2); P < 0.05] was greater in both men and women postrace. However, the amount of dobutamine required to induce these changes was greater in men, reflecting larger beta-receptor alterations in male triathletes following PSE relative to women. These data suggest that following an acute bout of PSE, male triathletes demonstrate an attenuated chronotropic and inotropic response to beta-adrenergic stimulation compared with female triathletes.

The human spleen during physiological stress.

Many mammals have the ability to autotransfuse a large quantity of red blood cells from the spleen into the active circulation during times of stress. This enhancement of the oxygen transport system has benefited the athletic mammal, that is, the thoroughbred horse, fox and greyhound in an improved aerobic performance. The role of the spleen in sequestering 50% of the total red cell volume in seals and horses, during times of inactivity, dramatically reduces the viscosity of the blood and therefore the work of the heart. In comparison, the human spleen contains only a small percentage of red blood cells, and has been primarily thought of as a lymphoid organ. The aim of this review is to emphasise the similarities between the human spleen and that of several athletic mammalian species during acute physiological stress. In the athletic mammalian model the expulsion of blood from the spleen is facilitated via the sympathetic nervous system resulting in contraction of smooth muscle within the splenic capsule. In comparison, the lack of smooth muscle contained within the human splenic capsule has meant that active contraction of the spleen has historically been viewed as unlikely, although evidence of contractile proteins within the red pulp have suggested otherwise. Exercise results in haemoconcentration, which has been attributed solely to a reduction in plasma volume. Indirect calculation of plasma volume changes utilise haemoglobin and haematocrit and assume that the circulating red cell volume remains constant. However, several studies have suggested that the human spleen could account for 30% of the increase in haematocrit. This would result in a substantial overestimation of the reduction in plasma volume, indicating that the expulsion of red blood cells from the spleen must not be overlooked when utilising these equations.

Evidence-based risk assessment and recommendations for physical activity clearance: an introduction.

The Physical Activity Readiness Questionnaire (PAR-Q) and the Physical Activity Readiness Medical Evaluation (PARmed-X) are internationally renowned and extensively used preparticipation screening tools. However, recent feedback from end-users has identified limitations to the existing PAR-Q and PARmed-X screening process. As such, a systematic evaluation of the PAR-Q and PARmed-X forms was conducted, adhering to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. Recognized experts in physical activity (PA) and prominent health conditions worked with an expert consensus panel to increase the effectiveness of the PAR-Q and PARmed-X PA participation clearance process. The systematic review process established that the health benefits of PA participation far outweigh the risks in the vast majority of asymptomatic and symptomatic individuals. A new risk continuum and decision tree process was created to allow for the effective risk stratification of prominent health conditions, reducing greatly the barriers to PA participation for the majority of individuals. The new PA participation clearance process is available in new paper and online versions (PAR-Q+) and the PARmed-X was replaced with an online interactive computer programme (ePARmed-X+). It is anticipated that this new risk stratification and PA clearance process will reduce markedly the barriers for PA participation for both asymptomatic and symptomatic individuals.

Evidence-based risk recommendations for best practices in the training of qualified exercise professionals working with clinical populations.

This systematic review examines critically "best practices" in the training of qualified exercise professionals. Particular attention is given to the core competencies and educational requirements needed for working with clinical populations. Relevant information was obtained by a systematic search of 6 electronic databases, cross-referencing, and through the authors' knowledge of the area. The level and grade of the available evidence was established. A total of 52 articles relating to best practices and (or) core competencies in clinical exercise physiology met our eligibility criteria. Overall, current literature supports the need for qualified exercise professionals to possess advanced certification and education in the exercise sciences, particularly when dealing with "at-risk" populations. Current literature also substantiates the safety and effectiveness of exercise physiologist supervised stress testing and training in clinical populations.

Evidence-based risk assessment and recommendations for physical activity clearance: Consensus Document 2011.

The Physical Activity Readiness Questionnaire (PAR-Q) and the Physical Activity Readiness Medical Evaluation (PARmed-X) are internationally known preparticipation screening tools developed on the basis of expert opinion. The primary purposes of this consensus document were to seek evidence-based support for the PAR-Q and PARmed-X forms, to identify whether further revisions of these instruments are warranted, to determine how people responding positively to questions on the PAR-Q can be safely cleared without medical referral, and to develop exercise clearance procedures appropriate for various clinical conditions across the human lifespan. Seven systematic reviews were conducted, examining physical-activity-related risks and effective risk-stratification procedures for various prevalent chronic conditions. An additional systematic review assessed the risks associated with exercise testing and training of the general population. Two gap areas were identified and evaluated systematically: the role of the qualified exercise professional and the requisite core competencies required by those working with various chronic conditions; and the risks associated with physical activity during pregnancy. The risks associated with being physically inactive are markedly higher than transient risks during and following an acute bout of exercise in both asymptomatic and symptomatic populations across the lifespan. Further refinements of the PAR-Q and the PARmed-X (including online versions of the forms) are required to address the unique limitations imposed by various chronic health conditions, and to allow the inclusion of individuals across their entire lifespan. A probing decision-tree process is proposed to assist in risk stratification and to reduce barriers to physical activity. Qualified exercise professionals will play an essential role in this revised physical activity clearance process.

Diastolic ventricular interactions in endurance-trained athletes during orthostatic stress.

Enhanced left-ventricular (LV) compliance is a common adaptation to endurance training. This adaptation may have differential effects under conditions of altered venous return. The purpose of this investigation was to assess the effect of cardiac (un)loading on right ventricular (RV) cavity dimensions and LV volumes in endurance-trained athletes and normally active males. Eight endurance-trained (Vo(2max), 65.4 +/- 5.7 ml.kg(-1).min(-1)) and eight normally active (Vo(2max), 45.1 +/- 6.0 ml.kg(-1).min(-1)) males underwent assessments of the following: 1) Vo(2max), 2) orthostatic tolerance, and 3) cardiac responses to lower-body positive (0-60 mmHg) and negative (0 to -80 mmHg) pressures with echocardiography. In response to negative pressures, echocardiographic analysis revealed a similar decrease in RV end-diastolic cavity area in both groups (e.g., at -80 mmHg: normals, 21.4%; athletes, 20.8%) but a greater decrease in LV end-diastolic volume in endurance-trained athletes (e.g., at -80 mmHg: normals, 32.3%; athletes, 44.4%; P < 0.05). Endurance-trained athletes also had significantly greater decreases in LV stroke volume during lower-body negative pressure. During positive pressures, endurance-trained athletes showed larger increases in LV end-diastolic volume (e.g., at +60 mmHg; normals, 14.1%; athletes, 26.8%) and LV stroke volume, despite similar responses in RV end-diastolic cavity area (e.g., at +60 mmHg: normals, 18.2%; athletes, 24.2%; P < 0.05). This investigation revealed that in response to cardiac (un)loading similar changes in RV cavity area occur in endurance-trained and normally active individuals despite a differential response in the left ventricle. These differences may be the result of alterations in RV influence on the left ventricle and/or intrinsic ventricular compliance.

Bronchial challenges in athletes applying to inhale a beta2-agonist at the 2004 Summer Olympics.

BACKGROUND: The International Olympic Committee Medical Commission required a medical justification for athletes to inhale a beta2-agonist before an event at the Summer Games in Athens in 2004. OBJECTIVE: We sought to establish the percentage of athletes applying to use an inhaled beta2-agonist on the basis of the results of objective tests to establish a diagnosis of asthma or exercise-induced bronchoconstriction. We also sought to compare this percentage with the percentage of athletes simply notifying the intention to use a beta2-agonist at the previous Summer Games in Sydney in 2000. METHODS: An analysis was made of tests that measured the change in FEV1 in response to a bronchodilator or in response to a provoking stimulus, such as exercise, eucapnic voluntary hyperpnea, hypertonic saline, or methacholine. RESULTS: Ten thousand six hundred fifty-three athletes competed in Athens; 4.2% were approved to use a beta2-agonist, and 0.4% were rejected. This approval rate was 26% less than the notifications in 2000 in Sydney (5.7%). Compared with Sydney 2000, there was a significant reduction of submissions and approvals for athletes from the United States, New Zealand, Australia, and Canada and in triathlon and swimming sports. CONCLUSION: The need to provide objective testing has resulted in a reduction in the number of athletes seeking approval to use an inhaled beta2-agonist. Objective evidence has provided information for the doctor that is likely to improve the health of the athlete because many athletes appeared to be undertreated at the time of testing. CLINICAL IMPLICATIONS: We show that documentation of airway narrowing in athletes, particularly in response to exercise or surrogate stimuli for exercise, aids in the diagnosis and management of asthma by providing evidence of bronchial hyperresponsiveness that will respond to treatment with inhaled corticosteroids and is usually associated with a reduction in respiratory symptoms on exercise.