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A Collaborative Approach to Integrative Physiology

Bengt Saltin was a distinguished scholar and mentor in the field of exercise physiology

When I’m running, I imagine a cacophony of sounds throughout my body—pop, bang, snap, pow, woosh—as electrical signals travel to my muscles, as calcium ions are released, as actin-myosin crossbridges form, as my lungs expand and contract, my heart rate increases, and dozens of other processes occur.

Portrait of Professor Bengt Saltin
Professor Bengt Saltin
CREDIT: Karin Söderlund, from Professor Bengt Saltin’s Memorial Fund through the Swedish School of Sport and Health Sciences, GIH.

Exercise triggers a cascade of signals that perturb homeostasis, and stimulate acute neurovascular, cardiovascular, and metabolic responses. Each of these systems may be examined in isolation but collaborating across fields and areas of expertise to study points of intersection—for example, blood flow and metabolism—provides greater insight into the mechanisms underlying the effects of exercise on human performance and disease states. Bengt Saltin (1935-2014) PhD, MD, was a champion of this collaborative approach, and demonstrated that exercise was an optimal tool for studying integrative physiology. Saltin’s experiments led to the development of the modern field of exercise physiology. His integrative and highly collaborative approach to research yielded more than 450 peer review articles. More importantly, his unique approach to leadership and efforts to foster collaboration among colleagues, peers, and trainees created new avenues of research and established a new generation of leaders in the field. 

Out of the woods

Saltin had an appreciation for sports, nature, and the outdoors from a young age and had aspirations of becoming a forestry officer. A knee injury sustained during a bandy match left him with plenty of time to study for matriculation exams, and the combination of excellent grades and his mother’s insistence steered Saltin from the woods to medical school. He obtained a medical degree from the Karolinska Institute in Stockholm in 1962. His research career began when his physiology teacher, Ulf von Euler, introduced him to professor Erik Howhü-Christensen at the Royal Gymnastic Central Institute in Stockholm. Saltin defended his doctoral thesis in 1964, accepted an associate professor position at the Karolinska Institute, and later a professorship at the August Krogh Institute in Copenhagen. 

Saltin’s career flourished over the next 50 years, and following his death, the Canadian Society for Exercise Physiology honored his life and contributions with a symposium in 2015. Speakers—including several of Saltin’s trainees—described Saltin’s role in developing the field of exercise physiology from “work physiology,” as well as his contributions across the fields of environmental physiology, exercise training and metabolism, human performance, altitude and sport physiology, and numerous others.1–4 In addition to celebrating his academic achievements, Saltin was lauded as a pioneer and advocate of the concept “exercise as medicine” and as a visionary leader at the Copenhagen Muscle Research Centre (CMRC).

Sidebar detailing some of Saltin's field expeditions
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Physician-physiologist

As a trained physician and physiologist, Saltin studied exercise through a variety of lenses. His research had implications for numerous populations, from professional and recreational athletes to cardiac patients.  

Putting bed rest to bed

In 1966, in a collaboration with researchers at the University of Texas, Southwestern Medical Center at Dallas, Saltin helped conduct a National Institutes of Health project that produced one of the most pivotal studies in exercise physiology. Results from the Dallas Bed Rest and Training study demonstrated the highly adaptive capacity of the cardiorespiratory system, a finding relevant to both athletes and patients in the clinical setting.

During the study, healthy 20-year-old male volunteers underwent three weeks of complete bed rest with zero weight bearing—mimicking the clinical treatment for acute myocardial infarction at the time—followed by about 55 days of aerobic exercise training. Cardiopulmonary function was assessed at baseline, after three weeks of bed rest, and after 55 days of training via maximal oxygen uptake (VO2max) during stress testing to exhaustion. VO2max is considered the best index of aerobic capacity and indicates the ability of the cardiovascular system to supply oxygen to working muscles as well as the muscles’ ability to extract the oxygen to generate energy.

The results were striking. Bed rest was associated with a 27 percent decrease in VO2max, a 26 percent decrease in cardiac output, and a 31 percent decrease in stroke volume. Just three weeks of bed rest among healthy individuals was hardly benign. It was actually harmful. 

In the clinic, cardiac rehabilitation has since displaced bed rest as the standard of care following myocardial infarction—as well as other diagnoses of cardiac dysfunction. It combines prescriptive exercise, cardiac risk-factor modification, and other elements to reduce morbidity and mortality. 

Unsurprisingly, the exercise training phase of the study induced more favorable adaptations. Exercise was associated with a 45 percent increase in VO2max, a 40 percent increase in maximal cardiac output, and a 48 percent increase in maximal stroke volume.5,6 

What made this study relevant to athletes was the mechanisms by which bed rest and training affected VO2max. In addition to measuring changes in central (cardiovascular) factors, the researchers measured changes in arteriovenous oxygen difference (muscle oxygen extraction), a key peripheral factor. Bed rest reduced VO2max primarily via central factors, whereas training enhanced VO2max through a combination of increased central and peripheral factors. 

Exercise as medicine

Since the bed rest study, other examples of Saltin’s work examined the effect of exercise training in a variety of clinical populations, including people with diabetes and heart failure, as well as aging populations. He was a pioneer and advocate for the concept of exercise as medicine.

In 2006 Saltin and his colleague Bente Klarlund Pedersen published a review of the evidence for prescribing exercise therapy as treatment for several diseases, including metabolic syndrome disorders, heart and pulmonary diseases, cancer, and depression, among others. In many cases, the evidence showed exercise therapy to be at least as effective as medical treatment, and in some cases it was even more effective. Saltin and Pedersen described exercise therapy not as a paradigm change, but as a necessity given the volume of evidence. 

In 2015, they published an updated review with evidence for prescribing exercise for 26 different diseases. The review encompassed the effects of exercise therapy on disease pathogenesis, symptoms, and explored possible mechanisms of action.

In addition to examining the scientific evidence, Saltin and Pedersen reiterated, “The accumulated knowledge is now so extensive that it has to be implemented.” They also emphasized the importance of a physically active lifestyle at the societal level, calling for improved infrastructure and accessibility:

“…It is now time that the health systems create the necessary infrastructure to ensure that supervised exercise can be prescribed as medicine. Moreover, it is important that society in general support a physical active lifestyle. People do not move when you tell them to. People move when the context compels them to do so. In order to enhance the physical activity level of the population, accessibility is important.”8

The concept of “exercise as medicine” has evolved into a United States-based health initiative. In 2007, the American College of Sports Medicine and the American Medical Association co-launched Exercise is Medicine® (EIM), with the goal of making physical activity assessment and promotion a standard in clinical care. EIM now exists in almost 40 countries.

Sidebar describing Saltin's involvement with sports and athletics
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The next generation

Saltin’s tenure as head of the CMRC from 1994-2004 is an important part of his legacy. In the early 1990s, he accepted an offer from the Danish National Research Foundation to develop the CMRC. He and seven other senior researchers in exercise physiology were to carry out the center’s goal—to focus on the regulation of skeletal muscle metabolism and its coupling to muscle blood flow—through an integrated approach to research. 

There was significant collaboration and interaction between researchers and labs from the August Krogh Institute, the Panum Institute, Bispebjerg Hospital, and the Capitol Hospital of Copenhagen, and various groups from abroad. 

A former senior scientist at the CMRC, Robert Boushel, noted that the combination of many students and visiting international scientists, among other factors, made the center “a ‘beehive’ of scientific collaboration.”4

Saltin is credited with supporting the development of numerous researchers in exercise physiology during his tenure at the CMRC. At least 15 students from the CMRC continued on to become full professors. Several of the speakers at the 2015 symposium honoring Saltin reflected on his benevolence. Boushel remarked: “He was very generous through providing opportunities and guidance to young scientists.” 4 According to one of Saltin’s postdoctoral trainees, Martin Gibala, “His scientific curiosity was perhaps exceeded only by his generosity.”3

In a perspective on Saltin’s impact and career, Michael Joyner, MD and physiologist, wrote:

“At some level, the best labs are like Montessori schools for bright young people. Bengt showed it was possible to run a large and high-powered research center at a major research center at a major research university in the same way.”

Imagine the possibilities for discovery and innovation should more leaders in the scientific community adopt this approach to leadership.

References:

1. Joyner, M. J. Bengt Saltin and exercise physiology: a perspective. https://doi.org/10.1139/apnm-2016-0314 42, 101–103 (2016).  

2. Ainslie, P. N. Professor Bengt Saltin Symposium – Environmental challenges to human performance. https://doi.org/10.1139/apnm-2016-0319 42, 104–107 (2016)

3. Gibala, M. J. Using exercise training to understand control of skeletal muscle metabolism. https://doi.org/10.1139/apnm-2016-0356 42, 108–110 (2016).

4. Boushel, R. Linking skeletal muscle blood flow and metabolism to the limits of human performance. https://doi.org/10.1139/apnm-2016-0393 42, 111–115 (2016). 

5. Saltin, B. et al. Response to exercise after bed rest and after training. Circulation 38, VII1-78 (1968). 

6. Mitchell, J. H., Levine, B. D. & McGuire, D. K. The Dallas bed rest and training study. Circulation 140, 1293–1295 (2019).

7. Pedersen, B. K. & Saltin, B. Evidence for prescribing exercise as therapy in chronic disease. Scand. J. Med. Sci. Sports 16 Suppl 1, 3–63 (2006).

8. Pedersen, B. K. & Saltin, B. Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand. J. Med. Sci. Sports 25, 1–72 (2015).

9. Helge, J. W. et al. Skiing across the Greenland icecap: divergent effects on limb muscle adaptations and substrate oxidation. J. Exp. Biol. 206, 1075–1083 (2003).