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Oxygen Status of Muscle During Exercise

Oxygen status of muscle during exercise in patients with interstitial lung disease – How much exercise is too much?

Submitted by Darlene Reid, BMR (PT), PhD

Background – Exercise is good but is it safe?

People with interstitial lung disease (ILD) have greatly reduced exercise capacity reflected by a 6-minute walk distance that is about 50 per cent lower and physical activity levels that are about one-third of those attained in healthy people.1-3 Pulmonary rehabilitation is an intervention recommended to individuals with chronic lung disease to improve symptoms, exercise capacity and health-related quality of life primarily through exercise training.4,5 Prescription of exercise for people living with ILD is often based on evidence derived from pulmonary rehabilitation for people with chronic obstructive pulmonary disease (COPD).  However, physiologic impairments appear to limit exercise to a greater extent in persons with ILD compared to those with COPD.6,7 For example, the exercise response in ILD is characterized by marked oxygen desaturation during relatively low levels of exercise.  Consequently, supplemental oxygen, especially during exertion, is more common and prescribed at higher flow rates in ILD compared to other chronic lung diseases.  We need to have a better understanding of how exercise impacts the oxygen status of muscle in ILD, especially in those with severe disease, in order to tailor recommendations for oxygen and exercise prescriptions.

What is the clinical problem?

A pulse oximeter estimates oxygen saturation in the peripheral circulating blood (SpO2). This information is used to titrate supplemental oxygen delivery to maintain an adequate level of oxygenation during exercise and determine the “safe” level of exercise intensity; however it provides no information about regional oxygenation of exercising muscle.  Near infrared spectroscopy (NIRS) is a non-invasive device that evaluates capillary oxygenation of the blood supplying underlying muscle tissue, a mix of venule and arteriole oxygenation.8,9  “NIRS is like an oximeter for muscle.”  Infrared light emitted from the device is absorbed by either oxy- or deoxy- hemoglobin and evaluation of this absorbance provides a measure of these two values.  Adding the two together provides an estimate of the total amount of hemoglobin and hence the total amount of blood (and oxygen) in the muscle beneath the NIRS device.  Using NIRS, we have shown that incremental loading of the biceps or the sternomastoid in stable COPD patients (none of whom were on supplemental oxygen) results in marked deoxygenation of the these two muscles.10  This pattern is quite different than that shown in healthy men where sternomastoid oxygenation status was maintained during incremental inspiratory threshold loading.11

How we began studying the problem?

With the support of funding from the Ontario Respiratory Care Society, a group of colleagues affiliated with the University of Toronto and Toronto General Hospital performed a study to examine the oxygen status of the muscles that are recruited during arm and leg exercise in people with mild ILD, severe (oxygen dependent) ILD and healthy people.  This study was led by Dr Darlene Reid (Principal Investigator), and co-investigators, Sunita Mathur, Lianne Singer and Lisa Wickerson.  However, Lisa Wickerson and Leandro Bonetti did all of the hard work of refining the methodology, recruiting participants, and collecting and analyzing the data.  Lisa performed this project as part of her PhD in the Rehabilitation Sciences Institute and Leandro Bonetti was a visiting scientist from Universidade de Caxias do Sul in Brazil.

The main exercises performed by study participants were incremental loading of the elbow flexors and the knee extensors on an isokinetic dynamometer, which is a computerized weight lifting device that can be programmed for specific types of exercise programs (see top pictures).  For both the elbow flexor and the knee extensor exercise, participants began at a very low level of intensity and then worked against higher and higher loads until they could no longer continue or were unable to do the exercise well.  NIRS devices were attached over the muscle that was doing the most work (see white arrows in pictures).  During this type of repetitive exercise, the NIRS device measures oxy-, deoxy- and total hemoglobin and estimates the saturation of oxygen in muscle, termed the SmO2.  The computer monitor displays SmO2 data (tracing) generated from an NIRS device during repetitive exercise, as shown on the right.  With repetitive muscle contraction the percentage of SmO2 in the vastus lateralis declines over time. The oscillations of the SmO2 tracing coincides with each muscle contraction.  The SmO2 begins at 68 per cent and drops to 54 per cent (number in the bottom left) after several contractions.  This value is lower than the usual resting SmO2 in muscle but further research is required to determine when this would be of concern, especially if the low value recovers within a short period of rest.  In other words, the dose response that causes injury is not known and likely relies on many other factors.

What did we discover?

Preliminary analysis of study findings is very interesting.  SmO2 decreased in participants with and without ILD but it dropped to a very low level at a much lower workload in those with severe ILD.  The workloads for both arm and leg exercise in IDL subjects was only about 50 per cent of the maximum workload attained in healthy people.  From a functional perspective, these results infer that SmO2 in people with severe ILD has a much higher probability of dropping to low levels during daily activities than in healthy people.  One of the next steps is to determine if the muscle has a good store of anti-oxidants eg. vitamin E, to sop up the oxidative stress imposed by low levels of  SmO2.  Persistent oxidative stress can increase reactive oxygen species that can damage cell membranes, increase oxidation of proteins and alter gene expression.12,13  In particular, activation of Hypoxia-Inducible-Factor-α can promote apoptosis, which is considered to be a primary contributor to muscle atrophy in people who live at high altitude and possibly in diseases that result in chronic hypoxemia.12 Thus, low SmO2 will not only reduce the workload that can be achieved but could result in oxidative stress that can trigger metabolic changes resulting in damage to  the muscle.

Another important finding of our study was that the SmO2 was not related to the SpO2 reading from the oximeter.  The clinical implication of this finding is that if one would like to know the oxygen status of muscle, NIRS monitoring will provide a more accurate evaluation than an oximeter.

Did we answer the big question – How much exercise is too much?

In the end, can we answer the question about how much exercise is too much? The short answer is “Not yet”.  Exercise training in pulmonary rehabilitation programs can definitely improve function and quality of life in people with ILD.  However, more work needs to be done to determine the most appropriate type and intensity of exercise, and whether supplemental oxygen and other interventions will temper the oxidative stress that occurs in muscle during exercise in people with ILD and other chronic lung diseases. The story continues.

The contribution of ORCS research funding to this study is gratefully acknowledged.

References

  1. Flaherty KR. IPF. Prognostic value of changes in physiology and 6 minute-walk test. Am J Respir Crit Care Med 2006; 174:803.
  2. Wallaert B, Monge E, Le Rouzic O, Wemeau-Stervinou L, Salleron J, Grosbois JM. Physical activity in daily life of patients with fibrotic idiopathic interstitial pneumonia. Chest 2013;144:1652–8.
  3. Wickerson L, Mathur S, Helm D, Singer L, Brooks D. Physical activity profile of lung transplant candidates with interstitial lung disease.  J Cardiopul Rehab Prevent 2013; 33(2):106-112.
  4. Spruit M, Singh S, Garvey C et al. An official ATS/ERS statement: key concepts and advances in pulmonary rehabilitation. Am J Resp Crit Care Med 2013;188:e13-e64.
  5. Dowman L. Hill CJ, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev 2014;10:CD006322.
  6. Markovitz GH, Cooper CB. Exercise and interstitial lung disease. Curr Opin Pulm Med 1998;4:272-280.
  7. Hansen JE, Wasserman K. Pathophysiology of activity limitation in patients with interstitial lung disease. Chest 1996;109:1566-1576.
  8. Boushel R, Langberg H, Olesen J, Gonzales-Alonzo J, Bulow J, Kjaer M. Monitoring tissue oxygen availability with near infrared spectroscopy (NIRS) in health and disease. Scand J Med Sci Sports 2001;11:213-22.
  9. Ferrari M, Mottola L, and Quaresima V. Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol 2004;29(4):463-487.
  10. Reid WD, Sheel AW, Shadgan B, Garland SJ, Road JD. Recruitment and deoxygenation of sternocleidomastoid and biceps during incremental loading in stable COPD patients. J Cardiopul Rehab Prevent 201
  11. Shadgan B, Guenette JA, Sheel AW, Reid WD. Sternocleidomastoid muscle deoxygenation in response to incremental inspiratory threshold loading measured by near infrared spectroscopy.  Respir Physiol Neuro 2011;178:202-209.
  12. Favier FB, Britto FA, Freyssenet DG, Bigard XA, Benoit H. HIF-1-driven skeletal muscle adaptations to chronic hypoxia.  Molecular insights into muscle physiology.   Cell Mol Life Sci 2015:72:4681–4696. DOI 10.1007/s00018-015-2025-9.
  13. Eliason JL, Wakefield TW. Metabolic consequences of acute limb ischemia and their clinical implications. Semin Vasc Surg 2009; 22:29-33.

Acknowledgement

We are grateful to the ORCS of The Lung Association – Ontario that provided funding in 2016 to perform this study.  We also very much appreciate the contributions of the participants who devoted their time in performing this study.

Darlene Reid, a member of ORCS, is a physiotherapist and professor in the Department of Physical Therapy at the University of Toronto.

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