Name: skeletal muscle neurovascular coupling, oxidative capacity, and microvascular function with 'one stop shop' near-infrared spectroscopy
Uploaded: 2018-02-20T15:00:00
Description: Watch this Scientific Journal Video about Skeletal Muscle Neurovascular Coupling, Oxidative Capacity, and Microvascular Function with 'One Stop Shop' Near-infrared Spectroscopy at JoVE.com

This work was supported by a University of Texas at Arlington Interdisciplinary Research Program grant.

This protocol follows the guidelines of the institutional review board at the University of Texas at Arlington and conforms to the standards set by the latest version of the Declaration of Helsinki. Accordingly, written informed consent was (and should be) obtained prior to commencement of research procedures.
1. Instrumentation
NOTE: The following instrumentation description is based on the near-infrared (NIR) spectrometer and data acquisition system used in our lab ...

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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=Muscle+function+and+quality+of+life+in+the+Crohn's+disease.">Muscle function and quality of life in the Crohn's disease.</a> Fisioter Mov. 30, 337-345 (2017).</li><li>Esch, B. T., Scott, J. M., Warburton, D. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Construction+of+a+lower+body+negative+pressure+chamber.">Construction of a lower body negative pressure chamber.</a> Adv Physiol Educ. 31 (1), 76-81 (2007).</li><li>Ryan, T. E., Southern, W. M., Reynolds, M. A., McCully, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+cross-validation+of+near-infrared+spectroscopy+measurements+of+skeletal+muscle+oxidative+capacity+with+phosphorus+magnetic+resonance+spectroscopy.">A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy.</a> J Appl Physiol. 115 (12), 1757-1766 (2013).</li><li>Ryan, T. E., Brophy, P., Lin, C. T., Hickner, R. C., Neufer, P. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+in+vivo+skeletal+muscle+mitochondrial+respiratory+capacity+in+humans+by+near-infrared+spectroscopy:+a+comparison+with+in+situ+measurements.">Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements.</a> J Physiol. 592 (15), 3231-3241 (2014).</li><li>Adami, A., Rossiter, H. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Principles,+insights+and+potential+pitfalls+of+the+non-invasive+determination+of+muscle+oxidative+capacity+by+near-infrared+spectroscopy.">Principles, insights and potential pitfalls of the non-invasive determination of muscle oxidative capacity by near-infrared spectroscopy.</a> J Appl Physiol. , (2017).</li><li>Corretti, M. C., 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=Guidelines+for+the+ultrasound+assessment+of+endothelial-dependent+flow-mediated+vasodilation+of+the+brachial+artery+-+A+report+of+the+International+Brachial+Artery+Reactivity+Task+Force.">Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery - A report of the International Brachial Artery Reactivity Task Force.</a> J Am Coll Cardiol. 39 (2), 257-265 (2002).</li><li>Thijssen, D. H., 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=Assessment+of+flow-mediated+dilation+in+humans:+a+methodological+and+physiological+guideline.">Assessment of flow-mediated dilation in humans: a methodological and physiological guideline.</a> Am J Physiol Heart Circ Physiol. 300 (1), H2-H12 (2011).</li><li>Green, D. J., Jones, H., Thijssen, D., Cable, N. T., Atkinson, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flow-mediated+dilation+and+cardiovascular+event+prediction:+does+nitric+oxide+matter?.">Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter?.</a> Hypertension. 57 (3), 363-369 (2011).</li><li>Southern, W. M., Ryan, T. E., Reynolds, M. 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L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+four+different+vascular+occlusion+tests+for+assessing+reactive+hyperemia+using+near-infrared+spectroscopy.">Comparison of four different vascular occlusion tests for assessing reactive hyperemia using near-infrared spectroscopy.</a> Crit Care Med. 39 (4), 695-701 (2011).</li><li>McLay, K. 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=Vascular+responsiveness+determined+by+near-infrared+spectroscopy+measures+of+oxygen+saturation.">Vascular responsiveness determined by near-infrared spectroscopy measures of oxygen saturation.</a> Exp Physiol. 101 (1), 34-40 (2016).</li><li>McLay, K. M., Nederveen, J. P., Pogliaghi, S., Paterson, D. H., Murias, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeatability+of+vascular+responsiveness+measures+derived+from+near-infrared+spectroscopy.">Repeatability of vascular responsiveness measures derived from near-infrared spectroscopy.</a> Physiol Rep. 4 (9), (2016).</li><li>Ryan, T. E., Southern, W. M., Brizendine, J. T., McCully, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Activity-induced+changes+in+skeletal+muscle+metabolism+measured+with+optical+spectroscopy.">Activity-induced changes in skeletal muscle metabolism measured with optical spectroscopy.</a> Med Sci Sports Exerc. 45 (12), 2346-2352 (2013).</li><li>Southern, W. 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=Reduced+skeletal+muscle+oxidative+capacity+and+impaired+training+adaptations+in+heart+failure.">Reduced skeletal muscle oxidative capacity and impaired training adaptations in heart failure.</a> Physiol Rep. 3 (4), (2015).</li><li>Ryan, T. E., Brizendine, J. T., McCully, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comparison+of+exercise+type+and+intensity+on+the+noninvasive+assessment+of+skeletal+muscle+mitochondrial+function+using+near-infrared+spectroscopy.">A comparison of exercise type and intensity on the noninvasive assessment of skeletal muscle mitochondrial function using near-infrared spectroscopy.</a> J Appl Physiol. 114 (2), 230-237 (2013).</li><li>Adami, A., Cao, R., Porszasz, J., Casaburi, R., Rossiter, H. 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The methods described herein enable non-invasive, clinical evaluation of reactive hyperemia, neurovascular coupling, and skeletal muscle oxidative capacity in a single clinic or laboratory visit.
Critical Considerations
Although NIRS is relatively robust and easy to use, collection of these data require careful placement of the optodes directly over the muscle belly, secured tightly in place to avoid movement artifact, and covered with a bl...

The hyperemic response to a brief period of tissue ischemia has emerged as a key non-invasive measure of (micro)vascular function. During occlusion of a conduit artery, downstream arterioles dilate in an effort to offset the ischemic insult. Upon release of the occlusion, the decreased vascular resistance results in hyperemia, the magnitude of which is dictated by one&#39;s ability to dilate the downstream microvasculature. While reactive hyperemia is a strong independent predictor of cardiovascular events1,2&#160;and therefore a clinically significant endpoint, its functional significance to exercise tolerance and quality of life is less clear.
Indeed, dynamic exercise represents a major cardiovascular stress that demands a highly coordinated neurovascular response in order to match oxygen delivery to metabolic demand. For example, skeletal muscle blood flow can increase nearly 100-fold during isolated muscle contractions3, which would overwhelm the pumping capacity of the heart if such a hemodynamic response were extrapolated to whole-body exercise. Accordingly, to avoid severe hypotension, sympathetic (i.e., vasoconstrictor) nervous activity increases to redistribute cardiac output away from inactive and visceral tissues and towards active skeletal muscle4. Sympathetic outflow is also directed to the exercising skeletal muscle5; however, local metabolic signaling attenuates the vasoconstrictor response in order to ensure adequate tissue oxygen delivery6,7,8,9,10,11. Collectively, this process is termed functional sympatholysis12, and is imperative to the normal regulation of skeletal muscle blood flow during exercise. Since skeletal muscle blood flow is a key determinant of aerobic capacity &#8212; an independent predictor of quality of life and cardiovascular disease morbidity and mortality13&#8212; understanding the control of skeletal muscle blood flow and tissue oxygen delivery during exercise is of great clinical significance.
Oxygen delivery is only half of the Fick equation, however, with oxygen utilization satisfying the other half of the equation. Among the major determinates of oxygen utilization, mitochondrial oxidative phosphorylation plays an essential role in supplying adequate energy for cellular processes both at rest and during exercise. Indeed, impairments in muscle oxidative capacity can limit functional capacity and quality of life14,15,16. Various measures are commonly used to provide an index of muscle oxidative capacity, including invasive muscle biopsies and expensive and time-consuming magnetic resonance spectroscopy (MRS) techniques.
Here, we propose a novel, non-invasive approach, using near-infrared spectroscopy (NIRS), to assess each of these three major clinical endpoints (reactive hyperemia, sympatholysis, and muscle oxidative capacity) in a single clinic or laboratory visit. The major advantages of this approach are three-fold: First, this technique is easily portable, relatively low cost, and easy to perform. Current Doppler ultrasound approaches for measuring reactive hyperemia are highly operator-dependent &#8212; requiring extensive skill and training &#8212; and require sophisticated, high-cost, data acquisition hardware and post-processing software. Moreover, this could conceivably be introduced into the clinic and/or large clinical trials for bedside monitoring or testing therapeutic efficacy. Second, by virtue of the methodology, this technique focuses specifically on the skeletal muscle microvasculature, increasing the overall specificity of the technique. Alternative approaches using Doppler ultrasound focus entirely on upstream conduit vessels and infer changes downstream, which can dampen the signal. Third, this technique is completely non-invasive. Skeletal muscle oxidative capacity is traditionally assessed with invasive and painful muscle biopsies, and functional sympatholysis may be assessed with intra-arterial injection of sympathomimetics and sympatholytics. This approach avoids these requirements all together.

<table border="0" cellpadding="0" cellspacing="0" width="836">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:328px;">Dual-channel OxiplexTS Near-infrared spectroscopy machine</td>
			<td style="width:223px;">Iss Medical</td>
			<td align="right" style="width:119px;">101</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">NIRS muscle sensor</td>
			<td style="width:223px;">Iss Medical</td>
			<td align="right" style="width:119px;">201.2</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">E20 Rapid cuff inflation system</td>
			<td style="width:223px;">Hokanson</td>
			<td style="width:119px;">E20</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">AG101 Air Source</td>
			<td style="width:223px;">Hokanson</td>
			<td style="width:119px;">AG101</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">Smedley Handgrip dynometer (recording)</td>
			<td style="width:223px;">Stolting</td>
			<td align="right" style="width:119px;">56380</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">Powerlab 16/35, 16 Channel Recorder</td>
			<td style="width:223px;">ADInstruments</td>
			<td style="width:119px;">PL3516</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">Human NIBP Set</td>
			<td style="width:223px;">ADInstruments</td>
			<td style="width:119px;">ML282-SM</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">Bio Amp</td>
			<td style="width:223px;">ADInstruments</td>
			<td style="width:119px;">FE132</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">Quad Bridge Amp</td>
			<td style="width:223px;">ADInstruments</td>
			<td style="width:119px;">FE224</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">Connex Spot Monitor</td>
			<td style="width:223px;">Welch Allyn</td>
			<td style="width:119px;">71WX-B</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:328px;">Origin(Pro) graphing software</td>
			<td style="width:223px;">OrignPro</td>
			<td style="width:119px;">Pro</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:328px;">Lower body negative pressure chamber</td>
			<td style="width:223px;">Physiology Research Instruments</td>
			<td style="width:119px;">standard unit</td>
			<td></td>
		</tr>
	</tbody>
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skeletal muscle neurovascular coupling, oxidative capacity, and microvascular function with 'one stop shop' near-infrared spectroscopy

Exercise represents a major hemodynamic stress that demands a highly coordinated neurovascular response in order to match oxygen delivery to metabolic demand. Reactive hyperemia (in response to a brief period of tissue ischemia) is an independent predictor of cardiovascular events and provides important insight into vascular health and vasodilatory capacity. Skeletal muscle oxidative capacity is equally important in health and disease, as it determines the energy supply for myocellular processes. Here, we describe a simple, non-invasive approach using near-infrared spectroscopy to assess each of these major clinical endpoints (reactive hyperemia, neurovascular coupling, and muscle oxidative capacity) during a single clinic or laboratory visit. Unlike Doppler ultrasound, magnetic resonance images/spectroscopy, or invasive catheter-based flow measurements or muscle biopsies, our approach is less operator-dependent, low-cost, and completely non-invasive. Representative data from our lab taken together with summary data from previously published literature illustrate the utility of each of these end-points. Once this technique is mastered, application to clinical populations will provide important mechanistic insight into exercise intolerance and cardiovascular dysfunction.

Skeletal muscle oxidative capacity
Figure 2 illustrates a representative participant response during a NIRS-derived skeletal muscle oxidative capacity assessment. Panel A shows the tissue saturation profile during a 5 min arterial cuff occlusion protocol, handgrip exercise, and intermittent arterial occlusion during recovery from exercise. Panel B illustrates the expected t...

Watch this Scientific Journal Video about Skeletal Muscle Neurovascular Coupling, Oxidative Capacity, and Microvascular Function with 'One Stop Shop' Near-infrared Spectroscopy at JoVE.com

Skeletal Muscle Neurovascular Coupling, Oxidative Capacity, and Microvascular Function with 'One Stop Shop' Near-infrared Spectroscopy

Here, we describe a simple, non-invasive approach using near-infrared spectroscopy to assess reactive hyperemia, neurovascular coupling and skeletal muscle oxidative capacity in a single clinic or laboratory visit.

Exercise represents a major hemodynamic stress that demands a highly coordinated neurovascular response in order to match oxygen delivery to metabolic ...

Research

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Medicine

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