Alaskan Sled Dogs Research Articles

Serum myostatin decreases in exercising and aging Alaskan sled dogs, while growth and differentiation factor 15 remains unaltered.

To evaluate the serum concentrations of myostatin and growth and differentiation factor 15 (GDF-15) in Alaskan Husky sled dogs participating in a 350-mile (560-km) race and in an older population, and to examine correlations between changes in serum concentrations and body condition scores (BCSs). Dogs were recruited from 3 teams of Alaskan Huskies participating in the Alaskan-Yukon Quest sled-dog race and retirees from a research sled-dog colony. Serum samples and BCSs were collected prior to racing, midway, and postrace; and in an older cohort (13 to 14 years). Myostatin and GDF-15 concentrations were assessed using commercially available ELISA kits. The median myostatin prerace concentration (9,519 pg/mL) was significantly greater than the mid- and postrace concentrations (7,709 pg/mL and 3,247 pg/mL, respectively). The prerace concentration was also significantly greater than that of the retired sled group dogs at 6,134 pg/mL. GDF-15 median serum concentrations did not change significantly across any racing time point (approx 350 pg/mL) or in the older cohort. No significant correlations were observed between changes in BCS and myostatin or GDF-15 concentrations. Serum myostatin decreases dramatically, yet no correlations to loss of BCS could be found. Myostatin signaling may be involved in maintaining hypertrophic signaling during intense exercise. Neither racing distance nor geriatric/retirement status appears to have an effect on serum GDF-15 concentration. Myostatin was less in the older, retired sled dogs compared to the younger racing cohort. Such differences highlight the roles that fitness level and age play regarding myostatin levels.

Genome Wide Association Study with Imputed Whole Genome Sequence Data Identifies a 431 kb Risk Haplotype on CFA18 for Congenital Laryngeal Paralysis in Alaskan Sled Dogs.

Congenital laryngeal paralysis (CLP) is an inherited disorder that affects the ability of the dog to exercise and precludes it from functioning as a working sled dog. Though CLP is known to occur in Alaskan sled dogs (ASDs) since 1986, the genetic mutation underlying the disease has not been reported. Using a genome-wide association study (GWAS), we identified a 708 kb region on CFA 18 harboring 226 SNPs to be significantly associated with CLP. The significant SNPs explained 47.06% of the heritability of CLP. We narrowed the region to 431 kb through autozygosity mapping and found 18 of the 20 cases to be homozygous for the risk haplotype. Whole genome sequencing of two cases and a control ASD, and comparison with the genome of 657 dogs from various breeds, confirmed the homozygous status of the risk haplotype to be unique to the CLP cases. Most of the dogs that were homozygous for the risk allele had blue eyes. Gene annotation and a gene-based association study showed that the risk haplotype encompasses genes implicated in developmental and neurodegenerative disorders. Pathway analysis showed enrichment of glycoproteins and glycosaminoglycans biosynthesis, which play a key role in repairing damaged nerves. In conclusion, our results suggest an important role for the identified candidate region in CLP.

Orthopedic and ultrasonographic examination findings in 128 shoulders of 64 ultra-endurance Alaskan sled dogs.

To determine the location and periarticular shoulder-muscle-abnormalities detected via orthopedic examinations and ultrasonography in ultra-endurance Alaskan sled-dogs, returned from an ultra-endurance sled-dog-race prior to finishing it. Prospective clinical study. Sixty-four dogs (128 shoulders). Dogs were classified based on clinical evidence of shoulder pain (SP versus control). Orthopedic examination findings, shoulder-abduction-angles (SAA; before- and during-anesthesia), and ultrasonographic findings were recorded. Relationships between orthopedic and ultrasonographic abnormalities were compared. Pain was elicited on 55/128 shoulders; 73 shoulders were pain-free. The most common painful structures included the biceps-tendon (BT; 30%), triceps-muscle (28%), and infraspinatus-muscle (25%). SAA ranged between 25° and 75° among groups, including pain-free shoulders in dogs without lameness. SAA was greater when dogs were anesthetized (46.3° ± 14.0° vs. 47.8° ± 12.0°; p = .03), especially in SP (mean increase of 3.49° ± 8.85°) compared to control (0.03° ± 7.71°, p = .009). Overall, 103 ultrasonographic abnormalities were detected (SP: 44; control: 59). The most common ultrasonographic abnormality was fluid surrounding the biceps tendon, similarly distributed between groups (SP: 39/44; control: 57/59). Most chronic ultrasonographic abnormalities affected the BT (15/103 abnormalities). No associations were detected between ultrasonographic abnormalities and clinical findings. Shoulder abduction varied greatly and reached up to 75° in normal joints. Ultrasonographic shoulder-muscle abnormalities were common but did not seem associated with clinical findings. Interpretation of shoulder abduction warrants caution, and the presence of fluid around the BT may reflect a physiologic adaptation to racing, rather than a pathologic change in ultra-endurance Alaskan sled-dogs.

Monitoring Brown Adipose Tissue in Alaskan Sled Dogs: A Pilot Study

Brown adipose tissue (BAT) has the unique function of burning energy to create heat through the process of non‐shivering thermogenesis. Activation of BAT in humans as a possible means of combating obesity is an active area of research, yet reliable methods for recognizing and monitoring BAT activation still need to be developed and validated. The purpose of this study was to assess the feasibility of thermal imaging for monitoring BAT activation in an in vivo animal model, specifically Alaskan sled dogs, which have been used extensively as models in cold‐weather metabolism and nutrition research. In this pilot study, BAT activation was monitored monthly over 4 months in a cohort of five sled dog puppies. Thermal images of the chest region and blood samples were collected before and after a cold exposure treatment. The thermal images were used to compare the temperature of the chest region pre‐ and post‐cold exposure, reasoning that a change in temperature would occur with BAT activation. Concentrations of two plasma biomarkers associated with non‐shivering thermogenesis, irisin and fibroblast growth factor 21 (FGF21), were measured in each blood sample. Although this pilot study did not have significant findings, it has produced a base of knowledge and methodology that is being used in current studies. Given the potential benefits of BAT activation for human health, the validation of thermal imaging as a non‐invasive monitoring technique and the use of an animal model could better inform the treatment of metabolic diseases.Support or Funding InformationFunding was provided by Nestlé Purina and the UAF BLaST Program. Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Numbers UL1GM118991, TL4GM118992, or RL5GM118990. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Serum metabolomics of Alaskan sled dogs during endurance racing

Long distance racing sled dogs are fed diets high in fat since lipid metabolism has long been thought to be the major substrate utilised during endurance racing. However, recent studies suggests that sled dogs are equally, if not more, dependent on carbohydrate metabolism. Considering the metabolic disparity regarding the energetics of endurance exercise, our study aimed to explore the serum metabolomic profiles of sled dogs running a 1,609 km (1000 mile) race. We hypothesised that there would be amino acid depletion due to gluconeogenesis and alteration in the citric acid cycle (CAC) based on the limited carbohydrate diet they consume. Serum was obtained from 6 Alaskan sled dogs approximately 24 h prior to the race (Whitehorse), at the midrace checkpoint (Dawson City), and again at the finish (Fairbanks). Serum was analysed using liquid chromatography-mass spectrometry for over 200 metabolites involved in amino acid, lipid, and carbohydrate metabolism with MetaboAnalyst Software 3.0. Major metabolic changes observed were decreased free fatty acids and enhanced acyl-carnitine derivatives during the race compared to baseline. Serum depletion of nearly all amino acids except for branched chain amino acids and phenylalanine was observed suggesting extensive protein catabolism. Many of the CAC intermediates were variable with increases in abnormal end glycation products. These results highlight that sled dogs display general amino acid depletion for pyruvate, acetyl CoA and CAC pathway intermediates with increased carnitine bound lipid metabolites, suggesting rate limiting beta-oxidation during endurance exercise, particularly at mid race. Further metabolomic studies to assess the influence of exercise and nutritional regimens are warranted to better understand substrate utilisation in working dogs.

Water requirements of canine athletes during multi‐day exercise

BackgroundExercise increases water requirements, but there is little information regarding water loss in dogs performing multi‐day exerciseObjectivesQuantify the daily water turnover of working dogs during multi‐day exercise and establish the suitability of SC administration of tracer to determine water turnover.AnimalsFifteen privately owned Labrador retrievers trained for explosive detection duties and 16 privately owned Alaskan Huskies conditioned for mid‐distance racing.MethodsAll dogs received 0.3 g D2O/kg body weight by IV infusion, gavage, or SC injection before the start of a multi‐day exercise challenge. Explosive detection dogs conducted 5 days of simulated off‐leash explosive detection activity. Alaskan sled dogs completed a mid‐distance stage race totaling 222 km in 2 days. Total body water (TBW) and daily water turnover were calculated using both indicator dilution and elimination regression techniques.ResultsTotal body water (% of body weight) varied from 60% ± 8.6% in minimally conditioned Labrador retrievers to 74% ± 4.5% in highly conditioned Labrador retrievers. Daily water turnover was as high as 45% of TBW during exercise in cold conditions. There was no effect of sex or speed on daily water turnover. There was good agreement between results calculated using the indicator dilution approach and those calculated using a semilog linear regression approach when indicator isotope was administered IV or SC.Conclusions and Clinical ImportanceWater requirements are influenced primarily by the amount of work done. SC administration of isotope‐labeled water offers a simple and accurate alternative method for metabolic studies.

Particulate Matter Exposure and Global DNA Methylation in Alaskan Sled Dogs: Sentinels for Human Health

Background: Ambient particulate matter (PM) concentrations are known to be associated with increased morbidity and mortality in human populations. During the winter months in Fairbanks, Alaska severe temperature inversions lead to elevated concentrations of ambient PM smaller than 2.5 microns (PM2.5). As there are multiple challenges in studying the impact of PM2.5 on people, sled dogs represent a high concentration easily accessible population that may yield findings relevant to human health risk. Objectives: In this pilot study, we evaluate sled dogs as a surrogate model for human PM exposure and associations with an epigenetic measure of global methylation. Methods: Kennels (n=3) were strategically recruited to provide a wide PM2.5 exposure gradient for the Fairbanks area. Continuous monitoring of ambient PM2.5 was conducted at each kennel during the winter of 2012/13 using a DustTrak 8530. Dogs received a physical evaluation and assessment of standard hematology and clinical chemistries. Global methylation was determined using the LUminometric Methylation Assay (LUMA). Results: Three sled dog kennels (n= ~30 dogs/kennel) were evaluated and sampled. The average PM2.5 concentrations measured for each kennel were 16 µg/m3, 48 µg/m3, 90 µg/m3 (p< 0.0001). The average (standard deviation) global methylation percentage for each kennel was 76.15 (1.80), 76.42 (1.92), and 76.73 (2.26), respectively. There was no statistical difference between the three kennels and their average global methylation percentage (p= 0.61). Conclusions: This is the first use of sled dogs as a surrogate for environmental exposure- related epigenetic effects. Average global methylation among dogs at each kennel had a monotonic relationship with average ambient PM2.5 concentrations, but differences were not statistically significant. Future studies could focus on repetitive elements and specific genes, which have human homologues.

Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia

BackgroundAchromatopsia is an autosomal recessive disease characterized by the loss of cone photoreceptor function that results in day-blindness, total colorblindness, and decreased central visual acuity. The most common causes for the disease are mutations in the CNGB3 gene, coding for the beta subunit of the cyclic nucleotide-gated channels in cones. CNGB3-achromatopsia, or cone degeneration (cd), is also known to occur in two canine breeds, the Alaskan malamute (AM) and the German shorthaired pointer.ResultsHere we report an in-depth characterization of the achromatopsia phenotype in a new canine breed, the miniature Australian shepherd (MAS). Genotyping revealed that the dog was homozygous for a complete genomic deletion of the CNGB3 gene, as has been previously observed in the AM. Identical breakpoints on chromosome 29 were identified in both the affected AM and MAS with a resulting deletion of 404,820 bp. Pooled DNA samples of unrelated purebred Australian shepherd, MAS, Siberian husky, Samoyed and Alaskan sled dogs were screened for the presence of the affected allele; one Siberian husky and three Alaskan sled dogs were identified as carriers. The affected chromosomes from the AM, MAS, and Siberian husky were genotyped for 147 SNPs in a 3.93 Mb interval within the cd locus. An identical shared affected haplotype, 0.5 Mb long, was observed in all three breeds and defined the minimal linkage disequilibrium (LD) across breeds. This supports the idea that the mutated allele was identical by descent (IBD).ConclusionWe report the occurrence of CNGB3-achromatopsia in a new canine breed, the MAS. The CNGB3-deletion allele previously described in the AM was also observed in a homozygous state in the affected MAS, as well as in a heterozygous carrier state in a Siberian husky and Alaskan sled dogs. All affected alleles were shown to be IBD, strongly suggesting an affected founder effect. Since the MAS is not known to be genetically related to the AM, other breeds may potentially carry the same cd-allele and be affected by achromatopsia.

An SNP within the Angiotensin-Converting Enzyme Distinguishes between Sprint and Distance Performing Alaskan Sled Dogs in a Candidate Gene Analysis

The Alaskan sled dog offers a unique mechanism for studying the genetics of elite athletic performance. They are a group of mixed breed dogs, comprised of multiple common breeds, and a unique breed entity seen only as a part of the sled dog mix. Alaskan sled dogs are divided into 2 primary groups as determined by their racing skills. Distance dogs are capable of running over 1000 miles in 10 days, whereas sprint dogs run much shorter distances, approximately 30 miles, but in faster times, that is, 18-25 mph. Finding the genes that distinguish these 2 types of performers is likely to illuminate genetic contributors to human athletic performance. In this study, we tested for association between polymorphisms in 2 candidate genes; angiotensin-converting enzyme (ACE) and myostatin (MSTN) and enhanced speed and endurance performance in 174 Alaskan sled dogs. We observed 81 novel genetic variants within the ACE gene and 4 within the MSTN gene, including a polymorphism within the ACE gene that significantly (P value 2.38 × 10(-5)) distinguished the sprint versus distance populations.

Efficacy of Omeprazole versus High-Dose Famotidine for Prevention of Exercise-Induced Gastritis in Racing Alaskan Sled Dogs

Omeprazole and famotidine both reduce severity of exercise-induced gastritis, but administering famotidine is easier than administering omeprazole during racing competition. Famotidine is more efficacious than no treatment in reducing severity of exercise-induced gastritis; and high-dose famotidine is more efficacious than omeprazole in reducing severity of exercise-induced gastritis. Experiment 1: Randomized placebo-controlled study, 36 sled dogs (3-8 years); Experiment 2: Randomized positive-control study, 52 sled dogs (2-8 years). Experiment 1: Equal numbers of dogs randomly assigned to famotidine (20 mg q24h) or no treatment groups. Gastroscopy was performed 24 hours after the dogs ran 330 miles. Mucosal appearance was blindly scored by previously described scoring system. Experiment 2: Equal numbers of dogs randomly assigned to omeprazole (20 mg q24h) or high-dose famotidine (40 mg q12h) groups. Gastroscopy was performed 48 hours before and 24 hours after the dogs ran 300 miles. Mucosal appearance was blindly scored by previously described scoring system. Famotidine reduced the prevalence of clinically relevant, exercise-induced gastric lesions compared with no treatment (7/16 versus 11/16, P = .031). Compared with high-dose famotidine, omeprazole significantly decreased the severity (0.4 versus 1.2, P = .0002) and prevalence (2/23 versus 7/21, P = .049) of gastric lesions. Although famotidine provides some benefit in the prevention of exercise-induced gastric lesions, omeprazole is superior to famotidine in preventing gastritis in dogs running 300 miles. Routine administration of omeprazole is recommended to prevent stress-associated gastric disease in exercising and racing Alaskan sled dogs.

Temporal pattern of skeletal muscle gene expression following endurance exercise in Alaskan sled dogs

Muscle responses to exercise are complex and include acute responses to exercise-induced injury, as well as longer term adaptive training responses. Using Alaskan sled dogs as an experimental model, changes in muscle gene expression were analyzed to test the hypotheses that important regulatory elements of the muscle's adaptation to exercise could be identified based on the temporal pattern of gene expression. Dogs were randomly assigned to undertake a 160-km run (n=9), or to remain at rest (n=4). Biceps femoris muscle was obtained from the unexercised dogs and two dogs at each of 2, 6, and 12 h after the exercise, and from three dogs 24 h after exercise. RNA was extracted and microarray analysis used to define gene transcriptional changes. The changes in gene expression after exercise occurred in a temporal pattern. Overall, 569, 469, 316, and 223 transcripts were differentially expressed at 2, 6, 12, and 24 h postexercise, respectively, compared with unexercised dogs (based on P<or=0.01 and an absolute fold change of >or=1.5). Increases in a number of known transcriptional regulators, including peroxisome proliferator-activated receptor-alpha, cAMP-responsive element modulator, and CCAAT enhancer binding protein-delta, and potential signaling molecules, including brain-derived neurotrophic factor, dermokine, and suprabasin, were observed 2 h after exercise. Biological functional analysis suggested changes in expression of genes with known functional relationships, including genes involved in muscle remodeling and growth, intermediary metabolism, and immune regulation. Sustained endurance exercise by Alaskan sled dogs induces coordinated changes in gene expression with a clear temporal pattern. RNA expression profiling has the potential to identify novel regulatory mechanisms and responses to exercise stimuli.

Assessment of alterations in triglyceride and glycogen concentrations in muscle tissue of Alaskan sled dogs during repetitive prolonged exercise

To assess changes in muscle glycogen (MG) and triglyceride (MT) concentrations in aerobically conditioned sled dogs during prolonged exercise. 54 Alaskan sled dogs fed a high-fat diet. 48 dogs ran 140-km distances on 4 consecutive days (cumulative distance, up to 560 km); 6 dogs remained as nonexercising control animals. Muscle biopsies were performed immediately after running 140, 420, or 560 km (6 dogs each) and subsequently after feeding and 7 hours of rest. Single muscle biopsies were performed during recovery at 28 hours in 7 dogs that completed 560 km and at 50 and 98 hours in 7 and 6 dogs that completed 510 km, respectively. Tissue samples were analyzed for MG and MT concentrations. In control dogs, mean +/- SD MG and MT concentrations were 375 +/- 37 mmol/kg of dry weight (kgDW) and 25.9 +/- 10.3 mmol/kgDW, respectively. Compared with control values, MG concentration was lower after dogs completed 140 and 420 km (137 +/- 36 mmol/kgDW and 203 +/- 30 mmol/kgDW, respectively); MT concentration was lower after dogs completed 140, 420, and 560 km (7.4 +/- 5.4 mmol/kgDW; 9.6 +/- 6.9 mmol/kgDW, and 6.3 +/- 4.9 mmol/kgDW, respectively). Depletion rates during the first run exceeded rates during the final run. Replenishment rates during recovery periods were not different, regardless of distance; only MG concentration at 50 hours was significantly greater than the control value. Concentration of MG progressively increased in sled dogs undergoing prolonged exercise as a result of attenuated depletion.

Effects of training and strenuous exercise on hematologic values and peripheral blood leukocyte subsets in racing sled dogs

To determine the effects of training and sustained submaximal exercise on hematologic values in racing sled dogs. Cohort study. 39 Alaskan sled dogs bred for endurance racing. Procedures-Blood samples were collected prior to initiation of a 7-month training regimen (n=39), after completion of the training regimen (19), and after completion of an 1,100-mile race (9), and a CBC, differential cell count, and flow cytometry for leukocyte surface antigens were performed. Both training and exercise caused significant decreases in PCV and hemoglobin concentration and significant increases in total WBC count. In contrast, training and exercise were not found to have significant effects on absolute numbers or fractions of CD4+ or CD8+ lymphocytes, other than a significant increase in the fraction of CD8+ lymphocytes associated with training. Results suggested that training and exercise induced changes in several hematologic values in racing sled dogs. Extracellular fluid volume expansion was the likely explanation for the training-induced decrease in PCV, and acute blood loss secondary to gastrointestinal tract bleeding was likely responsible for the decrease in PCV associated with acute exercise.

Efficacy of Famotidine for the Prevention of Exercise‐Induced Gastritis in Racing Alaskan Sled Dogs

Background: Omeprazole reduces the severity of exercise‐induced gastritis but not the prevalence of gastric lesions in sled dogs. The frequent feeding of sled dogs during competition likely results in decreased absorption of omeprazole and, thereby, decreased efficacy. Hypothesis: Famotidine, a histamine‐2 blocker with good bioavailability in the presence of food, would reduce the incidence and severity of exercise‐induced gastric disease in sled dogs. Animals: Sixteen fit Alaskan sled dogs (4 female, 12 male, all intact, age 2–6 years). Methods: Dogs were randomly assigned to treatment (22 mg famotidine PO q24h) or control groups (n = 8 per group). Famotidine was administered with a meal to the treatment group once daily for 7 days before a challenge and once during exercise. Control dogs were fed an identical diet as the principal group. The 16 dog team completed a 100‐mile exercise challenge in 18 hours. A gastroscopy was performed 24 hours after the challenge. The appearance of the mucosa was scored by an individual by using a scoring system. Results: Treatment with famotidine significantly reduced the severity score compared with control (P= .0004). No adverse effects of treatment were reported. Conclusions and Clinical Relevance: Famotidine is effective in reducing the severity of exercise‐induced gastric disease in racing Alaskan sled dogs, with minimal to no adverse effects, and may be recommended for prophylactic use in short distance races.

Efficacy of Famotidine for the Prevention of Exercise-Induced Gastritis in Racing Alaskan Sled Dogs

Omeprazole reduces the severity of exercise-induced gastritis but not the prevalence of gastric lesions in sled dogs. The frequent feeding of sled dogs during competition likely results in decreased absorption of omeprazole and, thereby, decreased efficacy. Famotidine, a histamine-2 blocker with good bioavailability in the presence of food, would reduce the incidence and severity of exercise-induced gastric disease in sled dogs. Sixteen fit Alaskan sled dogs (4 female, 12 male, all intact, age 2-6 years). Dogs were randomly assigned to treatment (22 mg famotidine PO q24h) or control groups (n = 8 per group). Famotidine was administered with a meal to the treatment group once daily for 7 days before a challenge and once during exercise. Control dogs were fed an identical diet as the principal group. The 16 dog team completed a 100-mile exercise challenge in 18 hours. A gastroscopy was performed 24 hours after the challenge. The appearance of the mucosa was scored by an individual by using a scoring system. Treatment with famotidine significantly reduced the severity score compared with control (P = .0004). No adverse effects of treatment were reported. Famotidine is effective in reducing the severity of exercise-induced gastric disease in racing Alaskan sled dogs, with minimal to no adverse effects, and may be recommended for prophylactic use in short distance races.

Temporal Relationship between Gastrointestinal Protein Loss, Gastric Ulceration or Erosion, and Strenuous Exercise in Racing Alaskan Sled Dogs

Background: Alterations in the appearance and function of gastrointestinal mucosa are common after strenuous exercise. However, the duration of exercise required to alter the gastrointestinal mucosa has not been reported. Hypothesis: We used 42 sled dogs to test the hypothesis that the magnitude of exercise‐induced gastrointestinal mucosal dysfunction is related to exercise duration. Animals: Six dogs served as conditioned controls, and the remaining dogs were randomly chosen for examination after 1–5 consecutive days of running at 100 miles/d. Methods: Gastroduodenoscopy and measurement of gastric permeability were performed 24 hours after cessation of exercise. Intestinal protein loss (represented by fecal alpha‐1 protease inhibitor concentration) was measured within 6 hours of cessation of exercise. Twelve of the 42 dogs were examined again after 5 months of detraining to determine the effect of training on gastrointestinal mucosal function. Results: Exercise increased gastric permeability (P= .04) and endoscopic severity of gastric lesions (P &lt; .0001), but neither variable was significantly affected by distance traveled. Acute exercise had no effect on intestinal protein loss. Untrained dogs had significantly lower fecal alpha‐1 protease inhibitor concentrations compared with trained, unexercised dogs. Training had no effect on gastric permeability to sucrose or the endoscopic appearance of the stomach. Conclusions and Clinical Importance: These data suggest that relatively modest exercise is required to increase intestinal protein loss, but more substantial exercise is required to cause alterations in the proximal gastrointestinal tract. However, none of these alterations appear to progress with increasing exercise duration.

Temporal Relationship between Gastrointestinal Protein Loss, Gastric Ulceration or Erosion, and Strenuous Exercise in Racing Alaskan Sled Dogs

Alterations in the appearance and function of gastrointestinal mucosa are common after strenuous exercise. However, the duration of exercise required to alter the gastrointestinal mucosa has not been reported. We used 42 sled dogs to test the hypothesis that the magnitude of exercise-induced gastrointestinal mucosal dysfunction is related to exercise duration. Six dogs served as conditioned controls, and the remaining dogs were randomly chosen for examination after 1-5 consecutive days of running at 100 miles/d. Gastroduodenoscopy and measurement of gastric permeability were performed 24 hours after cessation of exercise. Intestinal protein loss (represented by fecal alpha-1 protease inhibitor concentration) was measured within 6 hours of cessation of exercise. Twelve of the 42 dogs were examined again after 5 months of detraining to determine the effect of training on gastrointestinal mucosal function. Exercise increased gastric permeability (P = .04) and endoscopic severity of gastric lesions (P < .0001), but neither variable was significantly affected by distance traveled. Acute exercise had no effect on intestinal protein loss. Untrained dogs had significantly lower fecal alpha-1 protease inhibitor concentrations compared with trained, unexercised dogs. Training had no effect on gastric permeability to sucrose or the endoscopic appearance of the stomach. These data suggest that relatively modest exercise is required to increase intestinal protein loss, but more substantial exercise is required to cause alterations in the proximal gastrointestinal tract. However, none of these alterations appear to progress with increasing exercise duration.

Gender Differences in Baseline Levels of Vascular Endothelial Growth Factor in the Plasma of Alaskan Sled Dogs

Angiogenesis and vasculogenesis are two very important processes in the development and maintenance of mammalian health. In sled dogs, the angiogenic role is to supply and support tissue with ample vasculature, thus providing a route of access for the transportation of essential nutrients, including oxygen and the removal of waste in a sustained fashion. VEGF has been shown to be a key mediating factor in the underlying cascade of chemical events leading to angiogenesis, which makes it a very important precursor molecule for both muscle development and early neoplasia detection. The overall purpose of this study was to establish circulatory baseline VEGF levels in healthy dogs to develop an alternative mammalian model. Mean VEGF levels were 19 pg mL‾1 in sled dogs (n=20) and 5 pg mL‾1 in beagles (n=4). There were significant baseline VEGF-ir differences between male and female dogs and exercising males and exercising females. In addition preliminary data on beagles suggest that breed may play a role in baseline VEGF-ir levels. This study is the first step in the biotechnological development of a diagnostic VEGF assay in dogs.

Sustained Strenuous Exercise Increases Intestinal Permeability in Racing Alaskan Sled Dogs

We assessed gastric and intestinal permeability and performed gastroscopy to evaluate the effects of sustained strenuous exercise on the gastrointestinal tract in racing sled dogs. Three teams of racing Alaskan sled dogs were examined approximately 1 week before and 24 hours after the 2003 Iditarod sled dog race (1,100 miles in 10 days). Each examination consisted of the administration of a solution of sucrose, lactulose, and rhamnose to evaluate gastric and intestinal permeability, as well as gastroscopy to visually inspect the gastric mucosa. Of the 54 dogs examined before the race, 16 completed the course and contributed data to the analysis. Sustained strenuous exercise was associated with an increased frequency of gastric erosions or ulcerations seen endoscopically (0% prerace versus 61% postrace). A significant postrace increase occurred in the median lactulose to rhamnose ratio in both serum and urine (0.11 versus 0.165, P= .0363; 0.11 versus 0.165, P= .0090, respectively). No significant differences were found in median serum or urinary sucrose concentrations when pre‐ and postrace values were compared. No correlation was found between visible gastric lesions and the concentration of sucrose in serum or urine samples obtained 4–5 hours after administration of the sugar solutions. We conclude that sustained strenuous exercise is associated with increased intestinal permeability, but the sucrose permeability test as we performed it did not correlate with visible gastric lesions.

Sustained Strenuous Exercise Increases Intestinal Permeability in Racing Alaskan Sled Dogs

We assessed gastric and intestinal permeability and performed gastroscopy to evaluate the effects of sustained strenuous exercise on the gastrointestinal tract in racing sled dogs. Three teams of racing Alaskan sled dogs were examined approximately 1 week before and 24 hours after the 2003 Iditarod sled dog race (1,100 miles in 10 days). Each examination consisted of the administration of a solution of sucrose, lactulose, and rhamnose to evaluate gastric and intestinal permeability, as well as gastroscopy to visually inspect the gastric mucosa. Of the 54 dogs examined before the race, 16 completed the course and contributed data to the analysis. Sustained strenuous exercise was associated with an increased frequency of gastric erosions or ulcerations seen endoscopically (0% prerace versus 61% postrace). A significant postrace increase occurred in the median lactulose to rhamnose ratio in both serum and urine (0.11 versus 0.165, P = .0363; 0.11 versus 0.165, P = .0090, respectively). No significant differences were found in median serum or urinary sucrose concentrations when pre- and postrace values were compared. No correlation was found between visible gastric lesions and the concentration of sucrose in serum or urine samples obtained 4-5 hours after administration of the sugar solutions. We conclude that sustained strenuous exercise is associated with increased intestinal permeability, but the sucrose permeability test as we performed it did not correlate with visible gastric lesions.