Michael S. Davis

Repeated peripheral airway hyperpnea causes inflammation and remodeling in dogs.

INTRODUCTION/PURPOSE Elite winter athletes have an increased incidence of asthma, the cause of which is unknown. Strenuous exercise, particularly while breathing cold air, results in airway cooling and desiccation. We used a canine model of hyperpnea with cold, dry air to test the hypothesis that repeated cooling and desiccation of peripheral airways can cause asthma-like pathology. METHODS Canine sublobar airways were challenged with room temperature, dry air insufflated though a bronchoscope to simulate the mucosal cooling and desiccation that occurs in human peripheral airways during strenuous cold weather exercise. Airways were challenged once daily on four consecutive days, and control and challenged airways were harvested 24 h after the last challenge for histological analyses. RESULTS Repeated challenge caused airway obstruction and remodeling that persisted for at least 24 h. The percentage of mucosal squamous epithelium increased with a corresponding decrease in ciliated epithelium. Challenged airways had thicker lamina propria that contained greater concentrations of eosinophils, neutrophils, and mast cells when compared with control airways. The severity of airway obstruction was correlated with mucosal condition, airway thickness, and eosinophil infiltration. With the exception of mast cell infiltration, all changes were reversed within 1 wk of cessation of challenges. CONCLUSIONS We conclude that repeated cooling and desiccation of peripheral airways can cause airway remodeling similar to that seen in asthma. These findings, in concert with other reports using this model, support the hypothesis that asthma-like symptoms found in winter athletes may be the result of repeated hyperpnea with cold air.

Efficacy of omeprazole versus high-dose famotidine for prevention of exercise-induced gastritis in racing Alaskan sled dogs.

BACKGROUND Omeprazole and famotidine both reduce severity of exercise-induced gastritis, but administering famotidine is easier than administering omeprazole during racing competition. HYPOTHESIS 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. ANIMALS Experiment 1: Randomized placebo-controlled study, 36 sled dogs (3-8 years); Experiment 2: Randomized positive-control study, 52 sled dogs (2-8 years). METHODS 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. RESULTS 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. CONCLUSIONS AND CLINICAL RELEVANCE 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.

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

OBJECTIVE To assess changes in muscle glycogen (MG) and triglyceride (MT) concentrations in aerobically conditioned sled dogs during prolonged exercise. ANIMALS 54 Alaskan sled dogs fed a high-fat diet. PROCEDURES 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. RESULTS 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. CONCLUSIONS AND CLINICAL RELEVANCE 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

OBJECTIVE To determine the effects of training and sustained submaximal exercise on hematologic values in racing sled dogs. DESIGN Cohort study. ANIMALS 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. RESULTS 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. CONCLUSIONS AND CLINICAL RELEVANCE 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.

Participation in a 1,000-mile race increases the oxidation of carbohydrate in Alaskan sled dogs

The Alaskan Husky has been specifically bred for endurance performance and is capable of extreme endurance performance. We examined sled dogs in the trained state at the beginning of the race season and after a 1,600-km race (Iditarod). Our hypothesis was that lipids would be the predominant substrate during submaximal exercise in long-distance racing sled dogs, and a 1,600-km race would increase the reliance on lipids during an exercise bout at the same absolute exercise intensity. The experiments were completed over three testing periods, which were completed in January of two different years before participation in a 1,600-km race, or in March shortly after completion of a 1,600-km race. After determination of H(13)CO3 (-) recovery, the dogs were tested with primed continuous infusions of [1,1,2,3,3-(2)H]glycerol, [3-(13)C]lactate, or [6,6-(2)H2]glucose. During exercise, respiratory exchange ratio was significantly higher in raced (0.92 ± 0.01) compared with nonraced (0.87 ± 0.01) dogs. During exercise, glucose rate of appearance was potentially sustained by a large glycerol rate of disappearance with an increase in lactate rates of oxidation after a 1,600-km race. Therefore, contrary to our hypothesis, the sled dogs were dependent on carbohydrate energy sources, a reliance that increased further after participation in a 1,600-km race.

Bioelectrical impedance analysis determination of water content and distribution in the horse.

A horses hydration status is critical to its health. The accurate and quantitative determination of it has been problematic because of size, length and density of hair, and uneven topography. The objective of this study was to validate a bioelectrical impedance analysis (BIA) method for objectively quantifying hydration status. Monofrequency BIA values and simple biometric measurements were used to construct predictive equations for total body water, plasma, extracellular, and intra-cellular fluid volumes. These predictive equations were correlated with standard body fluid dilution reference methods. The result was an accuracy of ±0.64% for total body water, ±0.17% for plasma volume, ±1.91% for extra-cellular fluid, and ±0.57% for intra-cellular fluid compartments. Less than 5 min was required for all of the measurements and determinations. Therefore, it appears that an accurate measurement of body fluid distribution can be performed on horses using a fast, easy, non-invasive, inexpensive BIA method.

Gastritis in Alaskan racing sled dogs.

Alaskan racing sled dogs are a well-established model of exercise-induced gastric disease. The aim of this study was to define the temporal development of microscopical gastric lesions during long distance racing. Two groups of dogs were examined: group I comprised conditioned dogs that were exercising and group II were conditioned dogs not exercising. The gastric mucosa was examined endoscopically and sampled for routine histopathology and microscopical scoring, immunohistochemistry (IHC) and detection of apoptotic epithelial cells. Overall, group I dogs exhibited more significant epithelial lesions, including ulcers, compared with dogs in group II. Group II dogs exhibited the most severe mucosal inflammatory infiltrates. Although the intensity of inflammation differed, the nature of the inflammation was similar between groups, consisting of diffuse lymphocytic infiltration and a unique interface-type infiltrate that obscured the basement membrane zone and was accompanied by intraepithelial infiltration of lymphocytes. IHC confirmed the presence of CD3(+) T and CD79(+) B lymphocytes within the mucosal infiltrates; however, most of the intraepithelial and interface infiltrates were CD3(+) T cells. Spiral-shaped bacterial organisms were seen in the gastric tissues; however, their presence did not correlate with either the severity of epithelial lesions, inflammation or the pattern of interface inflammation. The number of apoptotic epithelial cells was widely variable and not significantly different between groups. These findings confirm previous observations that gastric ulcers develop in conditioned dogs under racing stress. The unique nature of the interface-type gastric inflammation is similar to that of human lymphocytic gastritis and may suggest an immune-mediated mechanism for the changes seen in Alaskan racing sled dogs.

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

Rationale Respiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions. Methods Newborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 107 FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses. Results Lambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and hyperplasia, peribronchial lymphocyte infiltration, and syncytial cells, were consistent with those described previously for lambs and infants. Conclusion This work demonstrates that M37 hRSV replication in the lower airways of newborn lambs is robust with peak replication on day 3 and sustained until day 6. These findings, along with the similarities of lamb lung to those of infants in terms of alveolar development, airway branching and epithelium, susceptibility to human RSV strains, lesion characteristics (bronchiolitis), lung size, clinical parameters, and immunity, further establish the neonatal lamb as a model with key features that mimic RSV infection in infants.

Principles and Applications of Therapeutic Exercises for Small Animals

Therapeutic exercises are the cornerstone of the rehabilitation programs of companion animals. Therapeutic exercises are used to improve active joint range of motion, to improve weight bearing and limb use, to build strength and muscle mass, and to increase conditioning (eg, endurance, speed). Each case is unique as chronicity, type of injury, patient signalment and temperament, owner compliance, and level of required functional recovery vary widely. Therapeutic exercises are also essential for partial return to work or performance and to learn to perform activities of daily living after injury or surgery.

Lack of microalbuminuria in sled dogs following exercise

Humans undergoing intense exercise exhibit transient microalbuminuria. Previous studies have shown that swimming, but not running, induces microalbuminuria in dogs. In this study, urine samples were collected from nineteen well-conditioned Alaskan sled dogs and analysed by the Heska ERD-Screen Test for microalbuminuria. None of the dogs has microalbuminuria, indicated that well-trained dogs do not develop microalbuminuria after running. Further studies are needed to determine if these dogs do develop microalbuminuria after competition or longer-distane runs.