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.
- Publications
- Miller B, Hamilton K, Boushel R, Williamson K, Laner V, Gnaiger E, Davis M. Mitochondrial respiration in highly aerobic canines in the non-raced state and after a 1600-km sled dog race. PLoS One. 2017 Apr 26;12(4)
- Gnaiger E, et al (MitoEAGLE Task Force). Mitochondrial Physiology. Bioenergetics Communications 2020; 2020.1: 1-44. doi:10.26124/bec:2020-0001.v1
- Davis MS, Fulton MR, Popken AA. Effect of hyperthermia and acidosis on equine skeletal muscle mitochondrial oxygen consumption. Comp Ex Phys, 2021: 17(2), 171–179. https://doi.org/10.3920/CEP200041
- Davis MS, Barrett MR. Effect of conditioning and physiology hyperthermia on canine skeletal muscle mitochondrial oxygen consumption. J Appl Physiol (1985). 2021 May 1;130(5):1317-1325. https://journals.physiology.org/doi/abs/10.1152/japplphysiol.00969.2020
- Davis MS, Barrett MR. High-Resolution Fluoro-Respirometry of Equine Skeletal Muscle. J. Vis. Exp. (192), e65075, doi: (2023).
- Freed AN and Davis MS. Effects of hyperventilation on peripheral airway surface fluid and airway resistance. Am.J.Respir.Crit.Care Med 1999; 159(4):1101-1107.
- Davis MS and Freed AN. Repetitive hyperventilation causes peripheral airway obstruction and eosinophilia. Eur Respir J 1999 Jul;14(1):57-62.
- Davis MS and Freed AN. Repeated Hyperventilation causes Peripheral Airways Inflammation, Hyperreactivity and Impaired Bronchodilation in Dogs. Am.J.Respir.Crit.Care Med 2001; 164(5):785-789.
- Davis MS, McCulloch S, Myers T, and Freed AN. Eicosanoids Modulate Hyperventilation-Induced Late Phase Airway Obstruction and Hyperreactivity, but not Inflammation, in Dogs. Respir Physiol 2002 Jan;129(3):357-65
- Davis MS*, Royer CM, Payton ME, Buttress B. Modeling the Late Phase Dose-Response Relationship to Peripheral Airway Hyperpnea. J Appl Physiol. 2002 Jul;93(1):195-200.
- Davis MS*, Lockard AJ, Marlin DJ, and Freed AN. Airway cooling and mucosal injury during cold weather exercise. Equine Vet J. Suppl 34:413-416, 2002.
- Davis MS*, McKiernan B, McCullough S, Nelson, SL, Mandsager RE, Willard M, and Dorsey K. Racing Alaskan Sled Dogs as a Model of “Ski Asthma.” Am J Respir Crit Care Med. 2002 Sep 15;166(6):878-82.
- Davis MS*, Schofield B, and Freed AN. Repeated Hyperventilation causes Peripheral Airways Inflammation and Remodeling in Dogs. Med Sci Sports Exerc. 2003 Apr;35(4):608-616.
- Davis MS*, Daviskas E, Anderson SD, Kotaru C, Hejal RB, Finigan JH, Coreno AJ, Skowronski ME, Brianas L, McFadden ER Jr. Airway surface fluid desiccation during isocapnic hyperpnea. J Appl Physiol. 2003 Jun;94(6):2545-7.
- Davis MS*, Williamson KK, McKenzie EC, Royer CM, Payton ME, Nelson SL. Effect of Training and Rest on Respiratory Mechanical Properties in Racing Sled Dogs. Med Sci Sports Exerc. 2005 Feb;37(2):337-341.
- Davis MS*, Malayer JR, VanDeventer L, Royer CM, McKenzie EC, Williamson KK. Cold Weather Exercise and Airway Cytokine Expression. J Appl Physiol. 2005 Jun;98(6):2132-6.
- Davis MS*, McKenzie EC, Royer CM, Williamson KK, Payton ME, Nelson SL. Effect of Training and Recovery on Airway Inflammation in an Animal Model of “Ski Asthma”. Eq Comp Exerc Physio. 2005 May;2(2):133-138.
- Davis MS*, Royer CM, McKenzie EC, Williamson KK, Payton ME, Marlin DM. Cold Air-Induced Late-Phase Bronchoconstriction in Horses. Equine Veterinary Journal 2006; 36:535-539.
- Davis, MS*, Williams CC, Meinkoth J, Malayer JR, Royer CM, Williamson KK, and McKenzie EC. Airway Neutrophil Influx and Persistence of Airway TH2 Cytokine Expression after Exercise while Breathing Cold Air. AJVR 2007 Feb;68(2):185-9.
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.
- Publications
- Davis MS, Hinchcliff KW, Williamson KK, McKenzie EC, Royer CM. Effect of multiday exercise on serum hormone and substrate concentrations in racing sled dogs. Comp Ex Phys 2020; 16(3): 197-205. https://doi.org/10.3920/CEP190068
- Davis MS. Glucocentric metabolism in ultra-endurance sled dogs. Integrative and Comparative Biology 2021 July 23; 6191):103-109. PMID: 33871632
- Tosi I, Art T, Boemer F, Votion DM, Davis MS. Acylcarnitine profile in Alaskan sled dogs during submaximal multiday exercise points out metabolic flexibility and liver role in energy metabolism. PLOS-One 2021 Aug 12;16(8):e0256009. PMID: 34383825
- Barrett MR, Davis MS. Conditioning-induced expression of novel glucose transporters in canine skeletal muscle homogenate. PLOS-One (2023).
- McKenzie EC, Jose-Cunilleras E, Hinchcliff KW, Holbrook TC, Royer CM, Payton ME, Williamson KK, Nelson SL, Willard MD, Davis MS*. Serum chemistry alterations in Alaskan Sled Dogs during five successive days of prolonged endurance exercise. JAVMA. 2007 May 15;230(10):1486-92.
- Davis MS*, Davis WC, Ensign W, Hinchcliff KW, Holbrook TC, and Williamson KK. Effects of training and strenuous exercise on hematologic values and peripheral blood leukocyte subsets in racing sled dogs. J Am Vet Med Assoc. 2008 Mar 15;232(6):873-8.
- McKenzie EC, Holbrook TC, Williamson KK, Valberg S, Hinchcliff K, Jose-Cunilleras E, Nelson S, Willard M, Davis MS*. Recovery of muscle glycogen concentrations in sled dogs during prolonged exercise. Med Sci Sports Exerc. 2005 Aug;37(8):1307-1312.
- Durocher L, Hinchcliff KW, Williamson KK, McKenzie EC, Holbrook TC, Willard MD, Royer CM, and Davis MS. Lack of microalbuminuria in sled dogs following exercise. Eq Comp Exerc Physio. 2006; 3(1): 1-2.
- McKenzie EC, Hinchcliff KW, Valberg S, Williamson KK, Payton ME, Davis MS*. Assessment of alterations in triglyceride and glycogen concentrations in muscle tissue of Alaskan sled dogs during repetitive prolonged exercise. Am J Vet Res. 2008 Aug;69(8):1097-103.
- McKenzie EC, Lupfer C, Banse HE, Hinchcliff KW, Love S, Nelson SL, Davis MS, Payton ME, Pastey M. Serum globulin and immunoglobulin concentrations in Alaskan sled dogs participating in a long-distance race. J Vet Intern Med. 2010 Jan-Feb;24(1):179-184.
- Davis MS*, Bonen A, Snook LA, Jain SS, Bartels K, Geor R, Hueffer K. Conditioning increases the gain of contraction-induced sarcolemmal substrate transport in ultra-endurance racing sled dogs. PLoS One. 2014 Jul 30;9(7).
- Miller BF, Drake JC, Peelor FF 3rd, Biela LM, Geor RJ, Hinchcliff KW, Davis M, Hamilton KL. Participation in a 1000-mile race increases the oxidation of carbohydrate in Alaskan sled dogs. J Appl Physiol (1985). 2014 Aug 21.
- Pratt-Phillips SE, Geor RJ, Buser M, Zirkle A, Moore A, Love SB, Entin P, Davis MS. Effect of a single bout of exercise and chronic exercise training on insulin sensitivity in racing sled dogs. Comp Ex Phys, 2014; 10(3):167-172
- Miller BF, Ehrlicher S, Drake JC, Peelor FF 3rd, Biela LM, Pratt-Phillips, S, Davis M, Hamilton KL. Assessment of protein synthesis in highly aerobic canine species at the onset and during exercise training. J Appl Physiol (1985). 2015 Apr 1;118(7):811-7.
- Pratt-Phillips S, Kutzner-Mulligan J, Davis MS. Energy intake and expenditure of improvised explosive device detection dogs. Comp Ex Phys 2015; 11(4): 249-254.
- Davis MS, Geor RJ, Williamson KK. Effect of Endurance Conditioning on Insulin-mediated Glucose Clearance in Dogs. Med Sci Sports Exerc. 2018 Jul 11. doi: 10.1249/MSS.0000000000001718.
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.
- Publications
- Mabry K, Davis MS, Gould E, Gogal RM, Steiner JM, Tolbert MK, Hill TL. Assessment of Exercise-Induced Gastrointestinal Syndrome in Racing Alaskan Sled Dogs using Capsule Endoscopy and Inflammatory Cytokines. Journal of Small Animal Practice (2023) https://doi.org/10.1111/jsap.13627
- Davis MS*, Willard MD, Nelson SL, McCullough SM, Mandsager RE, Roberts JE, Payton ME. Efficacy of omeprazole for the prevention of exercise-induced gastritis in racing Alaskan sled dogs. J Vet Intern Med. 2003 Mar-Apr;17(2):163-6.
- Davis MS*, Willard MD, Nelson SL, Mandsager RE, McKiernan BS, Mansell JK, Lehenbauer TW. Prevalence of Gastric Lesions in Racing Alaskan Sled Dogs. J Vet Intern Med. 2003 May-Jun;17(3):311-4.
- Davis MS*, Willard MD, Williamson KK, Steiner JM, Williams DA. Sustained Strenuous Exercise Increases Intestinal Permeability in Racing Alaskan Sled Dogs. J Vet Intern Med. 2005 Jan-Feb;19(1):34-39.
- Royer CM, Willard MD, Williamson KK, Steiner JM, Williams DA, Davis MS*. Exercise stress, intestinal permeability, and gastric ulceration in racing Alaskan sled dogs. Eq Comp Exerc Physio. 2005 Feb;2(1):53-59.
- Davis MS*, Willard MD, Williamson KK, Royer CM, Payton M, Steiner JM, Hinchcliff, KW, McKenzie EC, Nelson SL. The Temporal Relationship between Gastrointestinal Protein Loss, Gastric Ulceration or Erosion, and Strenuous Exercise in Racing Alaskan Sled Dogs. J Vet Intern Med. 2006; 20(4): 835-839.
- Williamson KK, Willard MD, McKenzie EC, Royer CM, Payton ME, Davis MS*. Efficacy of Famotidine for the Prevention of Exercise-Induced Gastritis in Racing Alaskan Sled Dogs. J Vet Intern Med. 2007 Sep-Oct;21(5):924-7.
- Williamson KK, Willard MD, Payton ME, Davis MS*. Efficacy of omeprazole versus high dose famotidine for prevention of exercise-induced gastritis in racing Alaskan sled dogs. J Vet Intern Med. 2010 Mar-Apr;24(2):285-288.
- Ritchey JW, Davis MS, Breshears MA, Willard MD, Williamson KK, Royer CM, Payton ME, Cragun AS. Gastritis in Alaskan Racing Sled Dogs. Journal of Comparative Pathology 2011 145: 68-76.
- Davis MS*, Willard MD, Bowers D, Payton Me. Effect of simulated deployment patrols on gastric mucosa of explosive detection dogs. Comp Ex Phys 2014 10(2): 99-103.
- Davis MS*, Willard MD, Day MJ, McCann J, Payton ME, Cummings SL Effect of Exercise on Gastric Health in Field Retrievers. Comp Ex Phys 2016; 12(1): 35-39.
- Davis MS*, Williamson KK. Gastritis and gastric ulcers in working dogs. Frontiers in Veterinary Science 2016; 3:30.
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.
- Publications
- Freed AN and Davis MS. Effects of hyperventilation on peripheral airway surface fluid and airway resistance. Am.J.Respir.Crit.Care Med 1999; 159(4):1101-1107.
- Davis MS and Freed AN. Repetitive hyperventilation causes peripheral airway obstruction and eosinophilia. Eur Respir J 1999 Jul;14(1):57-62.
- Davis MS and Freed AN. Repeated Hyperventilation causes Peripheral Airways Inflammation, Hyperreactivity and Impaired Bronchodilation in Dogs. Am.J.Respir.Crit.Care Med 2001; 164(5):785-789.
- Davis MS, McCulloch S, Myers T, and Freed AN. Eicosanoids Modulate Hyperventilation-Induced Late Phase Airway Obstruction and Hyperreactivity, but not Inflammation, in Dogs. Respir Physiol 2002 Jan;129(3):357-65
- Davis MS*, Royer CM, Payton ME, Buttress B. Modeling the Late Phase Dose-Response Relationship to Peripheral Airway Hyperpnea. J Appl Physiol. 2002 Jul;93(1):195-200.
- Davis MS*, Lockard AJ, Marlin DJ, and Freed AN. Airway cooling and mucosal injury during cold weather exercise. Equine Vet J. Suppl 34:413-416, 2002.
- Davis MS*, McKiernan B, McCullough S, Nelson, SL, Mandsager RE, Willard M, and Dorsey K. Racing Alaskan Sled Dogs as a Model of “Ski Asthma.” Am J Respir Crit Care Med. 2002 Sep 15;166(6):878-82.
- Davis MS*, Schofield B, and Freed AN. Repeated Hyperventilation causes Peripheral Airways Inflammation and Remodeling in Dogs. Med Sci Sports Exerc. 2003 Apr;35(4):608-616.
- Davis MS*, Daviskas E, Anderson SD, Kotaru C, Hejal RB, Finigan JH, Coreno AJ, Skowronski ME, Brianas L, McFadden ER Jr. Airway surface fluid desiccation during isocapnic hyperpnea. J Appl Physiol. 2003 Jun;94(6):2545-7.
- Davis MS*, Williamson KK, McKenzie EC, Royer CM, Payton ME, Nelson SL. Effect of Training and Rest on Respiratory Mechanical Properties in Racing Sled Dogs. Med Sci Sports Exerc. 2005 Feb;37(2):337-341.
- Davis MS*, Malayer JR, VanDeventer L, Royer CM, McKenzie EC, Williamson KK. Cold Weather Exercise and Airway Cytokine Expression. J Appl Physiol. 2005 Jun;98(6):2132-6.
- Davis MS*, McKenzie EC, Royer CM, Williamson KK, Payton ME, Nelson SL. Effect of Training and Recovery on Airway Inflammation in an Animal Model of “Ski Asthma”. Eq Comp Exerc Physio. 2005 May;2(2):133-138.
- Davis MS*, Royer CM, McKenzie EC, Williamson KK, Payton ME, Marlin DM. Cold Air-Induced Late-Phase Bronchoconstriction in Horses. Equine Veterinary Journal 2006; 36:535-539.
- Davis, MS*, Williams CC, Meinkoth J, Malayer JR, Royer CM, Williamson KK, and McKenzie EC. Airway Neutrophil Influx and Persistence of Airway TH2 Cytokine Expression after Exercise while Breathing Cold Air. AJVR 2007 Feb;68(2):185-9.
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.