Name: conducting maximal and submaximal endurance exercise testing to measure physiological and biological responses to acute exercise in humans
Uploaded: 2018-10-17T14:00:00
Description: Watch this Scientific Journal Video about Conducting Maximal and Submaximal Endurance Exercise Testing to Measure Physiological and Biological Responses to Acute Exercise in Humans at JoVE.com

This study was funded by the Mayo Clinic Department of Laboratory Medicine and Pathology and other various internal sources.

The protocol was approved by the Mayo Institutional Review Board and conformed to the Declaration of Helsinki. All participants provided written informed consent before participating in the testing described.
1. Calibration and Setup of Metabolic Cart
<ol>
	<li>Flow and volume (pneumotach) calibration 
	NOTE: Specific materials and equipment are listed in the Materials Table.
	<ol>
		<li>Open the pulmonary function and gas exchange software to calibrate for the test.</l...

<ol>
	<li>Caspersen, C. J., Powell, K. E., Christenson, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Physical+activity,+exercise,+and+physical+fitness:+definitions+and+distinctions+for+health-related+research.">Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research.</a> Public Health Reports. 100 (2), 126-131 (1985).</li><li>Pedersen, B. K., Saltin, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise+as+medicine+-+evidence+for+prescribing+exercise+as+therapy+in+26+different+chronic+diseases.">Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases.</a> Scandinavian Journal Medicine &amp; Science in Sports. 25, 1-72 (2015).</li><li>Barlow, C. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiorespiratory+fitness+is+an+independent+predictor+of+hypertension+incidence+among+initially+normotensive+healthy+women.">Cardiorespiratory fitness is an independent predictor of hypertension incidence among initially normotensive healthy women.</a> American Journal of Epidemiology. 163 (2), 142-150 (2006).</li><li>Blair, S. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Changes+in+physical+fitness+and+all-cause+mortality.">Changes in physical fitness and all-cause mortality.</a> A prospective study of healthy and unhealthy. 273 (14), 1093-1098 (1995).</li><li>Marson, E. C., Delevatti, R. S., Prado, A. K., Netto, N., Kruel, L. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+aerobic,+resistance,+and+combined+exercise+training+on+insulin+resistance+markers+in+overweight+or+obese+children+and+adolescents:+A+systematic+review+and+meta-analysis.">Effects of aerobic, resistance, and combined exercise training on insulin resistance markers in overweight or obese children and adolescents: A systematic review and meta-analysis.</a> Preventive Medicine. 93, 211-218 (2016).</li><li>Peel, J. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+prospective+study+of+cardiorespiratory+fitness+and+breast+cancer+mortality.">A prospective study of cardiorespiratory fitness and breast cancer mortality.</a> Medicine and Science in Sports and Exercise. 41 (4), 742-748 (2009).</li><li>Sui, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiorespiratory+fitness+and+adiposity+as+mortality+predictors+in+older+adults.">Cardiorespiratory fitness and adiposity as mortality predictors in older adults.</a> JAMA. 298 (21), 2507-2516 (2007).</li><li>Shulman, L. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Randomized+clinical+trial+of+3+types+of+physical+exercise+for+patients+with+Parkinson+disease.">Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease.</a> JAMA Neurology. 70 (2), 183-190 (2013).</li><li>Fleg, J. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise+training+as+therapy+for+heart+failure:+current+status+and+future+directions.">Exercise training as therapy for heart failure: current status and future directions.</a> Circulation. Heart Failure. 8 (1), 209-220 (2015).</li><li>Flynn, K. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+exercise+training+on+health+status+in+patients+with+chronic+heart+failure:+HF-ACTION+randomized+controlled+trial.">Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial.</a> JAMA. 301 (14), 1451-1459 (2009).</li><li>Scott, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+anthracycline-induced+cardiotoxicity+by+aerobic+exercise+in+breast+cancer:+current+evidence+and+underlying+mechanisms.">Modulation of anthracycline-induced cardiotoxicity by aerobic exercise in breast cancer: current evidence and underlying mechanisms.</a> Circulation. 124 (5), 642-650 (2011).</li><li>American College of Sports Medicine. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> ACSM's guidelines for exercise testing and prescription. , (2013).</li><li>Gustafson, M. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+systems+biology+approach+to+investigating+the+influence+of+exercise+and+fitness+on+the+composition+of+leukocytes+in+peripheral+blood.">A systems biology approach to investigating the influence of exercise and fitness on the composition of leukocytes in peripheral blood.</a> Journal for Immunotherapy of Cancer. 5, 30 (2017).</li><li>Freidenreich, D. J., Volek, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Immune+responses+to+resistance+exercise.">Immune responses to resistance exercise.</a> Exercise Immunology Review. 18, 8-41 (2012).</li><li>Campbell, J. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+exercise+mobilises+CD8++T+lymphocytes+exhibiting+an+effector-memory+phenotype.">Acute exercise mobilises CD8+ T lymphocytes exhibiting an effector-memory phenotype.</a> Brain Behavior and Immunity. 23 (6), 767-775 (2009).</li><li>Gustafson, M. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+method+for+identification+and+analysis+of+non-overlapping+myeloid+immunophenotypes+in+humans.">A method for identification and analysis of non-overlapping myeloid immunophenotypes in humans.</a> PLoS One. 10 (3), e0121546 (2015).</li><li>Miller, M. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardisation+of+spirometry.">Standardisation of spirometry.</a> European Respiratory Journal. 26 (2), 319-338 (2005).</li><li>Miller, M. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=General+considerations+for+lung+function+testing.">General considerations for lung function testing.</a> European Respiratory Journal. 26 (1), 153-161 (2005).</li><li>Borg, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ratings+of+perceived+exertion+and+heart+rates+during+short-term+cycle+exercise+and+their+use+in+a+new+cycling+strength+test.">Ratings of perceived exertion and heart rates during short-term cycle exercise and their use in a new cycling strength test.</a> International Journal of Sports Medicine. 3 (3), 153-158 (1982).</li><li>Norton, K., Norton, L., Sadgrove, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Position+statement+on+physical+activity+and+exercise+intensity+terminology.">Position statement on physical activity and exercise intensity terminology.</a> Journal of Science and Medicine in Sport. 13 (5), 496-502 (2010).</li><li>Lansley, K. E., Dimenna, F. J., Bailey, S. J., Jones, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+'new'+method+to+normalise+exercise+intensity.">A 'new' method to normalise exercise intensity.</a> International Journal of Sports Medicine. 32 (7), 535-541 (2011).</li><li>Poole, D. C., Burnley, M., Vanhatalo, A., Rossiter, H. B., Jones, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Critical+Power:+An+Important+Fatigue+Threshold+in+Exercise+Physiology.">Critical Power: An Important Fatigue Threshold in Exercise Physiology.</a> Medicine and Science in Sports and Exercise. 48 (11), 2320-2334 (2016).</li><li>Gustafsson, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+Acute+Exercise+on+Circulating+Soluble+Form+of+the+Urokinase+Receptor+in+Patients+With+Major+Depressive+Disorder.">Effects of Acute Exercise on Circulating Soluble Form of the Urokinase Receptor in Patients With Major Depressive Disorder.</a> Biomarker Insights. 12, 1177271917704193 (2017).</li><li>Hallberg, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise-induced+release+of+cytokines+in+patients+with+major+depressive+disorder.">Exercise-induced release of cytokines in patients with major depressive disorder.</a> Journal of Affective Disorders. 126 (1-2), 262-267 (2010).</li><li>Bengtsson Lindberg, M., Wilke, L., Vestberg, S., Jacobsson, H., Wis&#233;n, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise-induced+Release+of+Cytokines/Myokines+in+a+Single+Exercise+Test+before+and+after+a+Training+Intervention+in+Patients+with+Mild+Cognitive+Impairment.">Exercise-induced Release of Cytokines/Myokines in a Single Exercise Test before and after a Training Intervention in Patients with Mild Cognitive Impairment.</a> International Journal of Physical Therapy &amp; Rehabilitation. 3, (2017).</li></ol>

There is great potential for exercise to be incorporated as an adjunct/alternative therapeutic tool. Indeed, an emerging body of evidence strongly suggests that physical activity promotes good health. The use of exercise as a medicine or diagnostic tool would require an understanding of the right amount or &#34;dose&#34; of exercise to achieve the desired effect. The optimal dose of exercise should be estimated, as too much exercise may be detrimental to improving health. As such, an exercise regimen may need to be tailo...

Physical activity is defined as any bodily movement produced by skeletal muscles that require energy expenditure1. Exercise is a physical activity that involves repetitive bodily movement done to improve or maintain one or more components of physical health2. At one time, physical activity was not recommended for those who were seriously ill. For individuals with cancer, heart failure, or even for those who were pregnant, bed rest was preferred over physical activity. Clinical practice has since drastically changed, as the benefits of exercise on overall health are becoming undeniable3. Regular exercise has been shown to help reduce cardiovascular disease risk, all-cause mortality, cancer risk and hypertension, improve blood sugar control, facilitate weight loss or maintenance, and prevent bone and muscle loss4,5,6,7,8.
The extensive benefits of exercise have now led many to utilize exercise as a type of &#34;medicine&#34; and an alternative or adjunct treatment option for a variety of conditions3. Shulman et al. demonstrated that a combination of treadmill and resistance exercise could result in improvements in gait speed, aerobic capacity and muscular strength which could improve motor control and overall quality of life in patients with Parkinson&#39;s disease9. In heart failure patients, exercise intolerance and inadequate pharmaceutical interventions contribute to a poor quality of life10. Initial results from heart failure patients undergoing exercise training in the HF-ACTION trial demonstrated improvement in quality of life and reductions in hospitalizations and mortality11. Additionally, the application of exercise to alter the cardiotoxic effects of anthracycline-containing chemotherapy (e.g., doxorubicin) has demonstrated that regardless of when it is initiated with respect to the patients chemotherapy administration (before, during or after), exercise can provide beneficial effects such as reducing the decline in aerobic capacity, attenuating the left ventricular dysfunction and reducing oxidative damage12.
The benefits of exercise in health and wellness are not just in its application as a medicine/treatment, but also as a diagnostic tool. Exercise testing is, for example, used to diagnose exercise intolerance, ischemia in the heart, or to understand the cause of shortness of breath13. Perhaps more importantly, exercise testing may be utilized to identify subclinical dysfunction. The human body is in most situations &#34;overbuilt,&#34; such that dysfunction or pathophysiology can often remain hidden and unapparent to an individual for months or years. This observation may explain why conditions such as pulmonary arterial hypertension or pancreatic cancer can silently increase in severity such that by the time symptoms are noticed,&#160;these conditions tend to be very advanced and extremely difficult to treat2. In some of these situations, exercise testing can provide a stress stimulus to the body which increases demand above that of daily living and at times can identify dysfunction (cardiac, respiratory, metabolic) that was not seen at rest, helping to diagnose a disease and begin treatment earlier.
In order to fully maximize the therapeutic and diagnostic potential of exercise, standardized methods to quantify the responses to physical activity are needed to accurately assess the contributions of exercise to overall immune health. Variations in workload, inclination, duration, type of exercise, and the timing of sample collection can all influence measurements of physiological responses. Here, we outline methods for maximal and submaximal endurance exercises to gather physiological data while collecting samples for biological responses. This methodology was used to understand how acute exercise affected the distribution and frequency of leukocyte populations in peripheral blood14 by measuring&#160;immune cell populations at various time points before and after exercise by flow cytometry with 10-color flow protocols that permit the quantification of all major leukocyte subsets simultaneously15. The following protocol can be used as a standardized method for two distinct exercise regimens for measuring physiological and biological responses to exercise.

<table border="0" cellpadding="0" cellspacing="0" width="841">
	<tbody>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Metabolic cart/portable system</td>
			<td style="width:121px;">MCG Diagnostics</td>
			<td style="width:181px;">Mobile Ultima CPX System</td>
			<td style="width:323px;">The flow calibration syringe, and calibration gases should come with system. There are numerous possible options/alternatives.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Pulmonary function software (Breeze Suite)</td>
			<td>MCG Diagnostics</td>
			<td></td>
			<td style="width:323px;">Software used will depend on the metabolic system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Upright cycle ergometer</td>
			<td>Lode ergoline</td>
			<td>960900</td>
			<td>Numerous possible options/alternatives</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;">12-Lead ECG</td>
			<td>GE Healthcare</td>
			<td style="width:181px;">CASE Exercise Testing System</td>
			<td style="width:323px;">Used for 12 lead ECG capture, control bike. Having a full 12-lead is ideal for maximal exercise test so can monitor for arhythmias, but alternative for just HR would be a wireless chest strap heart rate monitor</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;">Pulse oximeter</td>
			<td>Masimo</td>
			<td>MAS-9500</td>
			<td style="width:323px;">Usually multiple probe options: finger, forehead, ear lobe.&#160; Usually avoid finger as tight handlebar grip can cause measurement inaccuracies</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Pneumotach (preVent Flow Sensor)</td>
			<td>MCG Diagnostics</td>
			<td>758100-003</td>
			<td>Alternative systems can use a turbine</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Nose piece (disposable)</td>
			<td>MCG Diagnostics</td>
			<td>536007-001&#160;</td>
			<td>Numerous possible options/alternatives</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">Mouthpeice with saliva trap</td>
			<td>MCG Diagnostics</td>
			<td>758301-001</td>
			<td style="width:323px;">Suggest filling the saliva trap with paper towel/gauze and tape cap to limit dripping</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">Headband</td>
			<td>Cardinal Health</td>
			<td>292866</td>
			<td style="width:323px;">Used to secure the forehead pulse oximeter and the lines for the cart</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Stethescope&#160;</td>
			<td>3M Littman</td>
			<td>3157SM</td>
			<td>Numerous possible options/alternatives</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">Blood pressure cuff</td>
			<td>HCS</td>
			<td>HCS9005-7</td>
			<td style="width:323px;">Cuff size will depend on the population planning to test</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">ECG Electrodes</td>
			<td>Cardinal Health</td>
			<td>M2570</td>
			<td>only needed with lead based ECG/HR monitoring</td>
		</tr>
		<tr height="26">
			<td height="26" style="height:26px;">K2EDTA tube 5mL</td>
			<td>Becton Dickinson</td>
			<td>368661</td>
			<td></td>
		</tr>
		<tr height="79">
			<td colspan="4" height="79" style="height:79px;width:841px;">*The table provides a list of the supplies and equipment utilized in this protocol and comments related to the equipment. Brand name/company is provided, but the use of other brands will not affect the results, key is to keep it consistent throughout testing in a particular study.</td>
		</tr>
	</tbody>
</table>

conducting maximal and submaximal endurance exercise testing to measure physiological and biological responses to acute exercise in humans

Regular physical activity has a positive effect on human health, but the mechanisms controlling these effects remain unclear. The physiologic and biologic responses to acute exercise are predominantly influenced by the duration and intensity of the exercise regimen. As exercise is increasingly thought of as a therapeutic treatment and/or diagnostic tool, it is important that standardizable methodologies be utilized to understand the variability and to increase the reproducibility of exercise outputs and measurements of responses to such regimens. To that end, we describe two different cycling exercise regimens that yield different physiologic outputs. In a maximal exercise test, exercise intensity is continually increased with a greater workload resulting in an increasing cardiopulmonary and metabolic response (heart rate, stroke volume, ventilation, oxygen consumption and carbon dioxide production). In contrast, during endurance exercise tests, the demand is increased from that at rest, but is raised to a fixed submaximal exercise intensity resulting in a cardiopulmonary and metabolic response that typically plateaus. Along with the protocols, we provide suggestions on measuring physiologic outputs that include, but are not limited to, heart rate, slow and forced vital capacity, gas exchange metrics, and blood pressure to enable the comparison of exercise outputs between studies. Biospecimens can then be sampled to assess cellular, protein, and/or gene expression responses. Overall, this approach can be easily adapted into both short- and long-term effects of two distinct exercise regimens.

The application of maximal or submaximal endurance exercise testing provides a stimulus or stressor in which the body responds to meet the increased physiological demands. Various modes of exercise can be used to compare the physiological and biological responses to a particular exercise by itself or when a drug/intervention is used, or to evaluate the differences in responses between different exercise loads. Maximal and endurance exercise loads differ in the duration (short/long respect...

Watch this Scientific Journal Video about Conducting Maximal and Submaximal Endurance Exercise Testing to Measure Physiological and Biological Responses to Acute Exercise in Humans at JoVE.com

Conducting Maximal and Submaximal Endurance Exercise Testing to Measure Physiological and Biological Responses to Acute Exercise in Humans

To assess the influence of exercise intensity on physiologic and biologic responses, two different exercise testing protocols were utilized. Methods outlining exercise testing on a cycle ergometer as an incremental maximal oxygen consumption test and endurance, steady state submaximal endurance test are described.

Regular physical activity has a positive effect on human health, but the mechanisms controlling these effects remain unclear. The physiologic and biologic ...

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Unit 1

An Overview of the Respiratory System: Anatomy, Physiology, Assessment, and Abnormalities

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Using Continuous Data Tracking Technology to Study Exercise Adherence in Pulmonary Rehabilitation

Pulmonary rehabilitation (PR) is an important component in the management of respiratory diseases. The effectiveness of PR is dependent upon adherence to exercise training recommendations. The study of exercise adherence is thus a key step towards the optimization of PR programs. To date, mostly indirect measures, such as rates of participation, completion, and attendance, have been used to determine adherence to PR. The purpose of the present protocol is to describe how continuous data tracking technology can be used to measure adherence to a prescribed aerobic training intensity on a second-by-second basis.
In our investigations, adherence has been defined as the percent time spent within a specified target heart rate range. As such, using a combination of hardware and software, heart rate is measured, tracked, and recorded during cycling second-by-second for each participant, for each exercise session. Using statistical software, the data is subsequently extracted and analyzed. The same protocol can be applied to determine adherence to other measures of exercise intensity, such as time spent at a specified wattage, level, or speed on the cycle ergometer. Furthermore, the hardware and software is also available to measure adherence to other modes of training, such as the treadmill, elliptical, stepper, and arm ergometer. The present protocol, therefore, has a vast applicability to directly measure adherence to aerobic exercise.

Pulmonary rehabilitation is widely recognized in the management of respiratory diseases. A key component to successful pulmonary rehabilitation is adherence to the recommended exercise training. The purpose of the present protocol is to describe how continuous data tracking technology can be used to precisely measure adherence to a prescribed aerobic training intensity.

Pulmonary rehabilitation (PR) is an important component in the management of respiratory diseases. The effectiveness of PR is dependent upon adherence to ...

Computerized Dynamic Posturography for Postural Control Assessment in Patients with Intermittent Claudication

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic conditions. As part of a diagnostic assessment, the early detection of postural deficits is important so that appropriate and targeted interventions can be prescribed. The Sensory Organization Test (SOT) on the EquiTest determines an individual&#39;s use of the sensory systems (somatosensory, visual, and vestibular) that are responsible for postural control. Somatosensory and visual input are altered by the calibrated sway-referenced support surface and visual surround, which move in the anterior-posterior direction in response to the individual&#39;s postural sway. This creates a conflicting sensory experience. The Motor Control Test (MCT) challenges postural control by creating unexpected postural disturbances in the form of backwards and forwards translations. The translations are graded in magnitude and the time to recover from the perturbation is computed.
Intermittent claudication, the most common symptom of peripheral arterial disease, is characterized by a cramping pain in the lower limbs and caused by muscle ischemia secondary to reduced blood flow to working muscles during physical exertion. Claudicants often display poor balance, making them susceptible to falls and activity avoidance. The Ankle Brachial Pressure Index (ABPI) is a noninvasive method for indicating the presence of peripheral arterial disease and intermittent claudication, a common symptom in the lower extremities. ABPI is measured as the highest systolic pressure from either the dorsalis pedis or posterior tibial artery divided by the highest brachial artery systolic pressure from either arm. This paper will focus on the use of computerized dynamic posturography in the assessment of balance in claudicants.

Individuals with intermittent claudication exhibit poor balance compared to healthy controls. Computerized dynamic posturography is an objective method for measuring an individual's postural responses to balance disturbances. This provides an objective reflection of the person&#x2019;s ability to respond to situations under which sensory stimuli are altered and unexpected perturbations occur.

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic ...

A Method to Study the Impact of Chemically-induced Ovarian Failure on Exercise Capacity and Cardiac Adaptation in Mice

The risk of cardiovascular disease (CVD) increases in post-menopausal women, yet, the role of exercise, as a preventative measure for CVD risk in post-menopausal women has not been adequately studied. Accordingly, we investigated the impact of voluntary cage-wheel exercise and forced treadmill exercise on cardiac adaptation in menopausal mice. The most commonly used inducible model for mimicking menopause in women is the ovariectomized (OVX) rodent. However, the OVX model has a few dissimilarities from menopause in humans. In this study, we administered 4-vinylcyclohexene diepoxide (VCD) to female mice, which accelerates ovarian failure as an alternative menopause model to study the impact of exercise in menopausal mice. VCD selectively accelerates the loss of primary and primordial follicles resulting in an endocrine state that closely mimics the natural progression from pre- to peri- to post-menopause in humans. To determine the impact of exercise on exercise capacity and cardiac adaptation in VCD-treated female mice, two methods were used. First, we exposed a group of VCD-treated and untreated mice to a voluntary cage wheel. Second, we used forced treadmill exercise to determine exercise capacity in a separate group VCD-treated and untreated mice measured as a tolerance to exercise intensity and endurance.

Two exercise paradigms were tested on a newly developed chemically induced menopausal mouse model to examine the impact of menopause on exercise capacity and cardiac adaption to exercise.

The risk of cardiovascular disease (CVD) increases in post-menopausal women, yet, the role of exercise, as a preventative measure for CVD risk in ...

A Methodological Approach to Non-invasive Assessments of Vascular Function and Morphology

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis. Damage to the endothelium may predispose the vessel to atherosclerosis and increase the risk for cardiovascular disease. Assessments of peripheral endothelial function are good indicators of early abnormalities in the vascular wall and correlate well with assessments of coronary endothelial function. The present manuscript details the important methodological steps necessary for the assessment of microvascular endothelial function using laser Doppler imaging with iontophoresis, large vessel endothelial function using flow-mediated dilatation, and carotid atherosclerosis using carotid artery ultrasound. A discussion on the methodological considerations for each of the techniques is also presented, and recommendations are made for future research.

The present article describes the methodological considerations for several non-invasive assessments of vascular function and morphology that are commonly used in medical research to assess different stages of atherosclerosis.

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis.  Damage to the endothelium may ...

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function

Mitochondrial dysfunction plays a significant role in the aging process and in neurodegenerative diseases including several hereditary spinocerebellar ataxias and other movement disorders marked by progressive degeneration of the cerebellum. The goal of this protocol is to assess mitochondrial dysfunction in Spinocerebellar ataxia type 1 (SCA1) and assess the efficacy of pharmacological targeting of metabolic respiration via the water-soluble compound succinic acid to slow disease progression. This approach is applicable to other cerebellar diseases and can be adapted to a host of water-soluble therapies.
Ex vivo analysis of mitochondrial respiration is used to detect and quantify disease-related changes in mitochondrial function. With genetic evidence (unpublished data) and proteomic evidence of mitochondrial dysfunction in the SCA1 mouse model, we evaluate the efficacy of treatment with the water-soluble metabolic booster succinic acid by dissolving this compound directly into the home cage drinking water. The ability of the drug to pass the blood brain barrier can be deduced using high performance liquid chromatography (HPLC). The efficacy of these compounds can then be tested using multiple behavioral paradigms including the accelerating rotarod, balance beam test and footprint analysis. Cytoarchitectural integrity of the cerebellum can be assessed using immunofluorescence assays that detect Purkinje cell nuclei and Purkinje cell dendrites and soma. These methods are robust techniques for determining mitochondrial dysfunction and the efficacy of treatment with water-soluble compounds in cerebellar neurodegenerative disease.

We present a biochemical and behavioral protocol to evaluate the efficacy of mitochondria-targeted water-soluble compounds for the treatment of Spinocerebellar ataxia type 1 (SCA1) and other cerebellar neurodegenerative diseases.

Mitochondrial dysfunction plays a significant role in the aging process and in neurodegenerative diseases including several hereditary spinocerebellar ...

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early cardiopulmonary dysfunction is difficult to diagnose, particularly in animal models, as cardiopulmonary function is often measured invasively, requiring anesthesia. As many anesthetic agents are cardiodepressive, subtle changes in cardiovascular function may be masked. In contrast, chronic instrumentation allows for measurement of cardiopulmonary function in the awake state, so that measurements can be obtained under quiet resting conditions, without the effects of anesthesia and acute surgical trauma. Furthermore, when animals are properly trained, measurements can also be obtained during graded treadmill exercise.
Flow probes are placed around the aorta or pulmonary artery for measurement of cardiac output and around the left anterior descending coronary artery for measurement of coronary blood flow. Fluid-filled catheters are implanted in the aorta, pulmonary artery, left atrium, left ventricle and right ventricle for pressure measurement and blood sampling. In addition, a 20 G&#160;catheter is positioned in the anterior interventricular vein to allow coronary venous blood sampling.
After a week of recovery, swine are placed on a motor-driven treadmill, the catheters are connected to pressure and flow meters, and swine are subjected to a five-stage progressive exercise protocol, with each stage lasting 3 min. Hemodynamic signals are continuously recorded and blood samples are taken during the last 30 sec of each exercise stage.
The major advantage of studying chronically instrumented animals is that it allows serial assessment of cardiopulmonary function, not only at rest but also during physical stress such as exercise. Moreover, cardiopulmonary function can be assessed repeatedly during disease development and during chronic treatment, thereby increasing statistical power and hence limiting the number of animals required for a study.

Here we present a protocol to assess cardiopulmonary function in awake swine, at rest and during graded treadmill exercise. Chronic instrumentation allows for repeated hemodynamic measurements uninfluenced by cardiodepressive anesthetic agents.

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early ...

Induction and Assessment of Exertional Skeletal Muscle Damage in Humans

Contraction-induced muscle damage via voluntary eccentric (lengthening) contractions offers an excellent model for studying muscle adaptation and recovery in humans. Herein we discuss the design of an eccentric exercise protocol to induce damage in the quadriceps muscles, marked by changes in strength, soreness, and plasma creatine kinase levels. This method is simple, ethical, and widely applicable since it is performed in human participants and eliminates the interspecies translation of the results. Subjects perform 300 maximal eccentric contractions of the knee extensor muscles at a speed of 120&#176;/sec on an isokinetic dynamometer. The extent of the damage is measurable using relatively non-invasive isokinetic and isometric measures of strength loss, soreness, and plasma creatine kinase levels over several days following the exercise. Therefore, its application can be directed to specific populations in an attempt to identify mechanisms for muscle adaptation and regeneration.

This article describes a safe and reliable method to induce and quantify exertional skeletal muscle damage in human subjects.

Contraction-induced muscle damage via voluntary eccentric (lengthening) contractions offers an excellent model for studying muscle adaptation and recovery ...

Integration of Brain Tissue Saturation Monitoring in Cardiopulmonary Exercise Testing in Patients with Heart Failure

Cerebral hypo-oxygenation during rest or exercise negatively impacts the exercise capacity of patients with heart failure with reduced ejection fraction (HF). However, in clinical cardiopulmonary exercise testing (CPET), cerebral hemodynamics is not assessed. NIRS is used to measure cerebral tissue oxygen saturation (SctO2) in the frontal lobe. This method is reliable and valid and has been utilized in several studies. SctO2 is lower during both rest and peak exercise in patients with HF than in healthy controls (66.3 &#177; 13.3% and 63.4 &#177; 13.8% vs. 73.1 &#177; 2.8% and 72 &#177; 3.2%). SctO2 at rest is significantly linearly correlated with peak VO2 (r = 0.602), oxygen uptake efficiency slope (r = 0.501), and brain natriuretic peptide (r = -0.492), all of which are recognized prognostic and disease severity markers, indicating its potential prognostic value. SctO2 is determined mainly by end-tidal CO2 pressure, mean arterial pressure, and hemoglobin in the HF population. This article demonstrates a protocol that integrates SctO2 using NIRS into incremental CPET on a calibrated bicycle ergometer.

This protocol integrated near-infrared spectroscopy into conventional cardiopulmonary exercise testing to identify the involvement of the cerebral hemodynamic response in exercise intolerance in patients with heart failure.

Cerebral hypo-oxygenation during rest or exercise negatively impacts the exercise capacity of patients with heart failure with reduced ejection fraction ...

Isolation of Intrapulmonary Artery and Smooth Muscle Cells to Investigate Vascular Responses

The intrapulmonary artery (IPA) and vascular smooth muscle cells (VSMCs) isolated from rat lungs can be used to study the underlying mechanisms of vasoconstriction and vasorelaxation. After isolating the IPA and VSMCs, the characteristics of vascular responses in physiological and pathological conditions can be assessed in the absence of extrinsic factors such as nerve signals, hormones, cytokines, etc. Thus, the IPA and VSMCs serve as excellent models for studying vascular physiology/pathophysiology, along with various experimental investigations, such as modulation by pharmacological agents, patch-clamp electrophysiological analysis, calcium imaging, etc. Here, we have used a technique for isolating the IPA to investigate vascular responses in an organ bath setup. IPA segments were mounted on the organ bath chamber via intraluminal wires and stimulated by various pharmacological agents. The changes in IPA vascular tone (i.e., vasoconstriction and vasorelaxation), were recorded using an isometric force transducer and physiological data analysis software program. We implemented several experimental protocols, which can be adapted to investigate the mechanisms of vasorelaxation/vasoconstriction for studying the pharmacological activities of phytochemical or synthetic drugs. The protocols can also be used to evaluate drugs&#39; roles in modulating various diseases, including pulmonary arterial hypertension. The IPA model allows us to investigate the concentration-response curve, which is crucial in assessing drugs&#39; pharmacodynamic parameters.

Vascular responses of arterial pulmonary circulation can be explored using intrapulmonary artery (IPA) and vascular smooth muscle cells (VSMCs). The present study describes the isolation of IPA in detail and the protocols used for investigating vasorelaxation in response to physiological stimuli.

The intrapulmonary artery (IPA) and vascular smooth muscle cells (VSMCs) isolated from rat lungs can be used to study the underlying mechanisms of ...

Muscle Function Obtained with Motion Mode Ultrasound and Surface Electromyography during Core Endurance Exercise

Motion mode (M-mode) ultrasound allows researchers and clinicians to measure the change of muscle thickness across time. Muscle thickness can be measured between fascial borders at a given time point during an exercise. This selected time point produces a one-dimensional image resulting in real-time, live observation of anatomy. Ultrasound used during functional movement can be referred to as dynamic ultrasound; this is feasible and reliable with the use of a linear transducer, elastic belt, and foam block to secure consistent transducer placement. The lateral abdominal wall is commonly investigated using ultrasound due to the overlapping nature of the muscles. Surface electromyography (sEMG) can complement M-mode ultrasound imaging because it measures the electrical representation of muscle activation. There is minimal evidence using M-mode ultrasound and sEMG simultaneously during core exercise. Exercises that challenge the core musculature involve both isometric holds (e.g., side plank), as well as oscillatory extremity movements (e.g., dead bug). In this study, both instruments will be used simultaneously to measure core muscle function during exercise. Ultrasound measurements will be obtained using a linear transducer and ultrasound unit, and sEMG measurements will be acquired from a wireless sEMG system. To make comparisons between participants and exercises, normalization methods using static, exercise starting positions for both instruments will be used. An activation ratio will be used for ultrasound and calculated by dividing the contracted thickness (thickness during a time point of exercise) by the rested (starting position) thickness. Muscle thickness will be measured in centimeters from the superior inferior fascial border to inferior superior fascial border. These methods aim to offer an innovative and practical measurement of muscle function with M-mode ultrasound and sEMG during core endurance exercises.

This protocol uses motion mode ultrasound and surface electromyography simultaneously to measure muscle function of the core. Muscle thickness and activation of the local stabilizers (e.g., transverse abdominis, internal oblique) and global movers (e.g., external oblique) is achievable during specific time points of the side plank and dead bug exercises.

Motion mode (M-mode) ultrasound allows researchers and clinicians to measure the change of muscle thickness across time. Muscle thickness can be measured ...