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College of
Veterinary Medicine

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DVM Program 
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About Programs and Admissions
DVM Program 
Graduate Program 
PAVE Program 
Student Life Research Continuing Education Alumni International Outreach

 

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Research Projects

The Comparative Exercise Physiology Lab (CEPL) has developed several large-scale research programs that remain active year after year and are supported by numerous individual research awards for different experiments.  All of these programs have in common the use of domestic animal athletes (dogs and horses) in support of research that is both translational (providing fundamental knowledge that can be extrapolated to other species such as humans) and clinically-applicable (directly relevant to professional and amateur animal athletes).

 

Effect of Physiological Extremes on Muscle Oxygen Consumption and ATP Production

Strenuous exercise requires a maximal rate of conversion of chemical energy to ATP for powering muscle contraction. Aerobic metabolism involves dozens of reactions coordinated by specific enzymes and produces large amount of heat as a by-product.  Build-up of this metabolic heat in the muscle cell or in the athlete can result in exercise failure. Additionally, high demand for ATP during maximal exercise can result in anaerobic metabolism, with lactic acid and decreased tissue pH as a consequence. The on-going focus of this project is to precisely characterize the heat and pH tolerance of skeletal muscle mitochondria and determine whether athletic conditioning results in specific substitution of key enzymes to isoforms more tolerant to physiochemical extremes.

 

Hydration and Thermoregulation During Exercise

A critical part of the metabolic load created by exercise is the management of the heat produced during exercise. Accumulation of body heat will ultimately degrade exercise performance through multiple mechanisms (including mitochondrial dysfunction being studied by the CEPL team), and can also lead to life-threatening heat injury.  Given that a major mechanism for dissipating heat into the environment is through evaporation of body water, heat management and hydration are inexorably linked and often studied together.  CEPL research has been critical in not only documenting the considerable water requirements that can accompany elite athletic performance, but also provided the public with proven methods for managing exercise hyperthermia to avoid injury.

  • Publications
    • Latman N, Keith N, Nicholson A, Davis M. Bioelectrical impedance analysis determination of water content and distribution in the horse.Res Vet SciPMID:20696446
    • Davis MS*, Cummings SL, Payton ME. Effect of brachycephaly and body condition score on canine respiratory thermoregulation during heat stress. JAVMA 2017. Nov 15;251(10):1160-1165. PMID:29099251
    • Baker JA, Davis MS. Effect of conditioning on exercise-induced hyperthermia and post-exercise cooling in dogs.  Comp Ex Phys 2018; 14(2):  91-97.  org/10.3920/CEP170039
    • Stephens-Brown L, Davis M. Water requirements of canine athletes during multi-day exercise. J Vet Intern Med. 2018 May;32(3):1149-1154. doi: 10.1111/jvim.15091. Epub 2018 Mar 23. PubMed PMID: 29572954; PubMed Central PMCID: PMC5980383 PMC5980383/
    • Davis MS, Marcellin-Little DJ, O’Connor E. Comparison of Post-exercise Cooling Methods in Working Dogs.  Journal of Special Operations Medicine, Spring 2019;19(1):56-60.  PMID:30859528
    • Schlader ZJ, Davis MS, Bouchama A. Biomarkers of heatstroke-induced organ injury and repair. Exp Physiol 2022 June 2. doi: 10.1113/EP090142
    • Davis MS. Effect of multiday endurance exercise on total body water and calculated body composition in racing sled dogs. Comparative Exercise Physiology 2023 19(1),  81–86. https://doi.org/10.3920/CEP220035.

 

Metabolic Strategy for Elite Ultraendurance Exercise

The ability of racing sled dogs to run for 100-150 miles per day and burn up to 12,000 calories per day, has intrigued exercise physiologists for the sheer magnitude of metabolic capacity that must be present and sustainable in these dogs. In particular, the United States Department of Defense has a long-standing interest in this physiology due to the similarities between what the dogs are demonstrably capable of doing and what they would like soldiers to be able to do while deployed (i.e., perform prolonged submaximal physical exertion for days to weeks without interruption, fatigue, or injury).

 

Starting in 2003, the Defense Advanced Research Projects Agency (DARPA) and later the Army Research Office began funding studies to characterize the molecular basis for high level, sustainable exercise metabolism by attempting to “reverse-engineer” elite racing sled dogs. The resulting studies have repeatedly challenged widely-held dogma in the exercise community of scientists, with published research demonstrating that the dogs are able to deplete, then replenish muscle glycogen “on the fly” and suggesting that their ability to rapidly adapt to the demands of prolonged strenuous exercise lies in their extremely high capacity for making and storing critical proteins in their muscles. This research has also demonstrated that despite their diet being very high in fat, their “preferred” substrate during exercise is glucose and they undergo extensive adaptations during their conditioning to increase their synthesis, uptake, and storage of glucose for use as exercise fuel. Most recently, this program has demonstrated that endurance-conditioned dogs upregulate several novel glucose transporters that likely explain the demonstrated increases in both basal and stimulated glucose uptake in muscle, and provide further support for a glucose-centric exercise metabolism in these dogs.

 

Exercise-Induced Gastrointestinal Disease in Dogs

Strenuous exercise has long been associated with signs and symptoms of gastrointestinal disease in humans and horses. Approximately 20 years ago, a similar association was suspected, but not proven in dogs. As a side-project associated with investigations into the effects of cold weather exercise on canine respiratory function, Dr. Davis and Dr. Mike Willard began an investigation into the prevalence of gastric ulcers in racing sled dogs. This area of research rapidly became a major focus with the discovery of extensive subclinical gastric ulcers and the need to establish preventative methods for the condition. This latter focus was led by Dr. Kathy Williamson, who in a series of studies established the efficacy of carefully-timed administration of omeprazole as the most effective means of preventing exercise-induced gastric ulcers in dogs. Once the leading cause of death in elite racing sled dogs, the widespread adoption of acid suppression medications during competition is credited by many racing officials as one of the major factors contributing to the reduction of dog deaths during multiday races.

 

Effect of Breathing Cold Air During Exercise in Horses and Dogs

When an animal inhales, the air entering its respiratory tract is “conditioned” to match the conditions of the animal; i.e., it is warmed and humidified, with the heat and water being supplied passively from the lining of the respiratory tract. Under temperate conditions, this process is largely limited to the upper airways so that by the time the inhaled air reaches the lungs, it is fully warmed and humidified and there is very little loss of heat and water from the lung tissue. However, if the air is very cold, and particularly if the subject is exercising hard enough to increase the amount of air being inhaled, the process of conditioning of the inhaled air extends into the lungs, resulting in heat and water being removed from the airway surfaces. It has been recognized for several decades that in subjects with pre-existing asthma, this process could provoke an acute asthmatic attack known to physicians as exercise-induced asthma. However, it has more recently been recognized that the effects were not limited to subjects with pre-existing asthma – epidemiological studies of elite cold weather athletes suggested that exercising in extremely cold environments could actually cause repeated injury to the airways, ultimately leading to an asthma-like condition commonly known as “ski asthma.”

Starting with the work he did during his Ph.D., and later using funding from the State of Oklahoma, the National Institutes of Health, and the American College of Veterinary Internal Medicine, Dr. Davis was the first to prospectively demonstrate that repeated breathing of cold air during exercise could create all of the signs of asthma in a normal subject. These studies not only helped explain the very high incidence of asthma in elite winter athletes, but they have also identified an important cause of airway inflammation in racehorses and have helped influence the environmental standards used by racetracks for guiding training and racing. More recently, studies have identified an additional potential consequence: alteration of host immunity to respiratory pathogens as a result of breathing cold air.  This is the current focus of this research program.

 

Adaptation of Athletic Dogs to High Altitude

A unique aspect of living and working at high altitude is the reduced availability of oxygen to support aerobic metabolism. Over time, various populations have been able to adapt to moderate altitudes (up to 15,000 feet), but acute exposure to low ambient oxygen levels can imposed severe limitations to exercise and even in adapted populations, maximal capacity for aerobic metabolism is lower than at sea level. This project characterized the acute responses of athletic dogs to acute exposure to simulated high altitude in order to identify potential therapeutic targets in both dogs and humans to accelerate restoration of athletic performance during intermittent high altitude activities. Due to the sensitive nature of these studies with regards to military operations (various agencies within the Department of Defense have sponsored these studies), no publications will arise from these studies and dissemination of the results is limited to the sponsoring agencies.

 

Non-programmatic Research Projects

  • Publications

    Effect of brachycephaly on thermoregulation

    Davis MS*, Cummings SL, Payton ME. Effect of brachycephaly and body condition score on canine respiratory thermoregulation during heat stress. JAVMA 2017. Nov 15;251(10):1160-1165. .

    Hyperthermia and water requirements of exercising dogs

    Stephens-Brown L, Davis M. Water requirements of canine athletes during multi-day exercise. J Vet Intern Med. 2018 May;32(3):1149-1154. doi:

    10.1111/jvim.15091.

    Predicting fitness for ultraendurance exercise

    Love SB, Davis MS, Goad C, Murphy K, Aichele DB, Fossum TW. Predictive Hematological and Serum Biomarkers for Canine Endurance Exercise. Comparative Exercise Physiology 2011 7(3): 109-115.

    Effectiveness of pre-exercise massage

    Huneycutt HW, Davis MS.  Effect of pre-exercise massage on exercise-induced muscle injury in dogs.  Comp Ex Phys 2015; 11(4): 245-248.

    Non-invasive measurement of body water compartments in horses

    Latman N, Keith N, Nicholson A, Davis M.  Bioelectrical impedance analysis determination of water content and distribution in the horse. Res Vet Sci. 2010 Aug 7.

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