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Abstract

Objective—To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics.

Animals—24 horses.

Procedures—Horses were randomly allocated to 3 treatment groups and received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone plus oats, or oats alone (control) for 15 days, followed by IV infusion of lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently sampled IV glucose tolerance tests were performed prior to pretreatment, after pretreatment, and 20 hours after lipopolysaccharide administration. Area under the curve for plasma glucose and serum insulin concentrations was calculated, and minimal model analyses were performed.

Results—Significant treatment-by-time effects were detected for insulin sensitivity (SI) and area under the curve for glucose and insulin in the 15-day pretreatment period. Insulin sensitivity significantly decreased over time in all treatment groups, with the largest decrease detected in the dexamethasone group. Administration of lipopolysaccharide further decreased mean SI by 71% and 63% in the dexamethasone and control groups, respectively, but did not affect horses in the levothyroxine group. Mean SI was the lowest in the dexamethasone group, but percentage reduction was the same for dexamethasone and control groups.

Conclusions and Clinical Relevance—Insulin sensitivity decreased during the pretreatment period in all 3 groups, indicating that hospitalization affected glucose and insulin dynamics. Dexamethasone significantly lowered SI, and endotoxemia further exacerbated insulin resistance. In contrast, there was no additional effect of endotoxemia on SI in horses pretreated with levothyroxine, suggesting that this treatment prevented endotoxemia-induced insulin resistance.

Full access
in American Journal of Veterinary Research

Abstract

Objective

To determine whether furosemide treatment altered the blood flow properties and serum and RBC electrolyte concentrations of Thoroughbreds during submaximal treadmill exercise.

Design

Thoroughbreds were subjected to submaximal treadmill exercise with and without treatment with furosemide (1 mg/kg of body weight, IV).

Animals

5 healthy Thoroughbreds that had raced within the past year and had no history of exercise-induced pulmonary hemorrhage.

Procedure

Venous blood samples were obtained before exercise, at treadmill speeds of 9 and 13 m/s, and 10 minutes after exercise, and hemorheologic and electrolyte test results were determined.

Results

Hemorheologic changes 60 minutes after furosemide administration included increased PCV, plasma total protein concentration, whole blood viscosity, mean RBC volume, and RBC potassium concentration, and decreased serum potassium concentration, serum chloride concentration, and RBC chloride concentration. Furosemide treatment attenuated the exercise-associated changes in RBC size, serum sodium concentration, serum potassium concentration, RBC potassium and chloride concentrations, and RBC density; exacerbated exercise-associated increases in whole blood viscosity; and had no effect on RBC filterability.

Conclusions

The hemorheologic effects of furosemide probably occurred secondary to total body and transmembrane fluid and electrolyte fluxes and would not improve blood flow properties.

Clinical Relevance

The beneficial effects of furosemide treatment in reducing the severity of bleeding in horses with exercise-induced pulmonary hemorrhage cannot be explained by improved blood flow properties. (Am J Vet Res 1996;57:891–895)

Free access
in American Journal of Veterinary Research

Abstract

Objectives

To determine whether pentoxifylline treatment altered hematologic, rheologic, electrolyte, or blood gas test results of Thoroughbreds during submaximal treadmill exercise.

Animals

5 healthy Thoroughbreds that had raced within the past year and had no history of exercise-induced pulmonary hemorrhage.

Procedure

Mixed venous blood samples were obtained before exercise, at treadmill speeds of 9 and 13 m/s, and 20 minutes after exercise; hematologic, rheologic, electrolyte, and blood gas test results were determined.

Results

Pentoxifylline treatment resulted in a 45% reduction in RBC filtration pressures for horses at rest. The improved RBC filterability persisted during treadmill exercise. Horses treated with pentoxifylline had a greater decrease in Po2 values and a lesser increase in plasma lactate concentration during treadmill exercise.

Conclusion

Administration of pentoxifylline improved RBC deformability of horses at rest and during treadmill exercise.

Clinical Relevance

Improved RBC deformability resulting from pentoxifylline treatment may reduce exercise-associated shear stress in pulmonary capillaries, thereby attenuating exercise-induced pulmonary hemorrhage. (Am J Vet Res 1996;57:1364-1368)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of dexamethasone treatment on selected components of insulin signaling and glucose metabolism in skeletal muscle obtained from horses before and after administration of a euglycemic-hyperinsulinemic clamp (EHC).

Animals—6 adult Standardbreds.

Procedures—In a balanced crossover study, horses received either dexamethasone (0.08 mg/kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution, IV, for 21 days. A 2-hour EHC was administered for measurement of insulin sensitivity 1 day after treatment. Muscle biopsy specimens obtained before and after the EHC were analyzed for glucose transporter 4, protein kinase B (PKB), glycogen synthase kinase (GSK)-3α/β protein abundance and phosphorylation state (PKB Ser473 and GSK-3α/β Ser21/9), glycogen synthase and hexokinase enzyme activities, and muscle glycogen concentration.

Results—Dexamethasone treatment resulted in resting hyperinsulinemia and a significant decrease (70%) in glucose infusion rate during the EHC. In the dexamethasone group, increased hexokinase activity, abrogation of the insulin-stimulated increase in glycogen synthase fractional velocity, and decreased phosphorylation of GSK-3α Ser21 and GSK-3B Ser9 were detected, but there was no effect of dexamethasone treatment on glucose transporter 4 content and glycogen concentration or on PKB abundance and phosphorylation state.

Conclusions and Clinical Relevance—In horses, 21 days of dexamethasone treatment resulted in substantial insulin resistance and impaired GSK-3 phosphorylation in skeletal muscle, which may have contributed to the decreased glycogen synthase activity seen after insulin stimulation.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare effects of low and high intensity warm-up exercise on oxygen consumption (O2) and carbon dioxide production (CO2 ) in horses. Animals—6 moderately conditioned adult Standardbreds.

Procedures—Horses ran for 2 minutes at 115% of maximum oxygen consumption (O2max), 5 minutes after each of the following periods: no warm-up (NoWU); 10 minutes at 50% of O2max (LoWU); or 7 minutes at 50% O2max followed by 45-second intervals at 80, 90, and 100% O2max (HiWU). Oxygen consumption and CO2 were measured during exercise, and kinetics of O2 and CO2 were calculated. Accumulated O2 deficit was also calculated.

Results—For both warm-up trials, the time constant for the rapid exponential increase in O2 was 30% lower than for NoWU. Similarly, the rate of increase in CO2 was 23% faster in LoWU and HiWU than in NoWU. Peak values for O2 achieved during the highspeed test were not significantly different among trials (LoWU, 150.2 ± 3.2 ml/kg/min; HiWU, 151.2 ± 4.2 ml/kg/min; NoWU, 145.1 ± 4.1 ml/kg/min). However, accumulated O2 deficit (ml of O2 equivalents/kg) was significantly lower during LoWU (65.3 ± 5.1) and HiWU (63.4 ± 3.9) than during NoWU (82.1 ± 7.3).

Conclusions and Clinical Relevance—Both the lowand high-intensity warm-up, completed 5 minutes before the start of high-intensity exercise, accelerated the kinetics of O2 and CO2 and decreased accumulated O2 deficit during 2 minutes of intense exertion in horses that were moderately conditioned. (Am J Vet Res 2000;61:638–645)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate the effects of a continuous rate infusion (CRI) of dextrose solution or dextrose solution and insulin on glucose and insulin concentrations in healthy and endotoxin-exposed horses.

Animals—9 adult mares.

Procedures—During phase 1, treatments consisted of saline (0.9% NaCl) solution (control group; n = 4) or 20% dextrose solution (group 1; 4) administered IV as a 360-minute CRI. During phase 2, treatments consisted of 360-minute CRIs of 20% dextrose solution and insulin administered simultaneously at 367.6 mg/kg/h (30 kcal/kg/d) and 0.07 U/kg/h, respectively, in healthy horses (group 2; n = 4) or horses administered 35 ng of lipopolysaccharide/kg, IV, 24 hours before starting the dextrose solution and insulin CRIs (group 3; 4). A balanced crossover study design was used in both phases. Blood samples were collected for measurement of plasma glucose and insulin concentrations.

Results—Infusion of dextrose solution alone resulted in hyperglycemia for most of the 360-minute CRI. Insulin concentration increased significantly in group 1, compared with that in the control group. Mean insulin concentration of group 2 was significantly higher throughout most of the infusion period, compared with concentrations of the control group and group 1. Mean glucose concentration did not differ significantly between groups 2 and 3.

Conclusions and Clinical Relevance—Insulin infusion at a rate of 0.07 U/kg/h was found to be effective for the prevention of hyperglycemia when administered concurrently with dextrose solution. This rate was considered to be safe because horses did not become hypoglycemic during infusions of dextrose solution.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of refeeding following an 18-hour period of feed withholding on the phosphorylation of translation initiation factors in the skeletal muscle of mature horses.

Animals—8 adult horses.

Procedures—Following an 18-hour period of feed withholding, horses either continued to have feed withheld (postabsorptive state) or were fed 2 g/kg of a high-protein feed (33% crude protein) at time 0 and 30 minutes (postprandial state). Blood samples were taken throughout the experimental period. At 90 minutes, a biopsy specimen was taken from the middle gluteal muscle to measure the phosphorylation of translation initiation factors and tissue amino acid concentrations. Plasma glucose, insulin, and amino acid concentrations were also measured.

Results—Horses in the postprandial state had significantly higher plasma insulin, glucose, and amino acid concentrations than did those in the postabsorptive state at the time of biopsy. Refeeding significantly increased the phosphorylation state of riboprotein S6 and eukaryotic initiation factor 4E binding protein 1.

Conclusions and Clinical Relevance—In mature horses, feeding resulted in increased mammalian target of rapamycin signaling and the mechanism appeared to be independent of an increase in Akt phosphorylation at Ser473. Results indicate that adult horses may be able to increase rates of muscle protein synthesis in response to feeding and that dietary amino acids appear to be the main mediators of this effect.

Full access
in American Journal of Veterinary Research

Abstract

Objective

To compare dew-point hygrometry, direct sweat collection, and measurement of body water loss as methods for determination of sweating rate (SR) in exercising horses.

Animals

6 exercise-trained Thoroughbreds.

Procedure

SR was measured in 6 horses exercising at 40% of the speed that elicited maximum oxygen consumption for 45 km, with a 15-minute rest at the end of each 15-km phase. Each horse completed 2 exercise trials. Dew-point hygrometry, as a method of local SR determination, was validated in vitro by measurement of rate of evaporative water loss. During exercise, local SR was determined every 10 minutes by the following 2 methods: (1) dew-point hygrometry on the neck and lateral area of the thorax, and (2) on the basis of the volume of sweat collected from a sealed plastic pouch attached to the lateral area of the thorax. Mean whole body SR was calculated from total body water loss incurred during exercise.

Results

Evaporation rate measured by use of dewpoint hygrometry was significantly correlated (r 2 = 0.92) with the actual rate of evaporative water loss. There was a similar pattern of change in SR measured by dew-point hygrometry on the neck and lateral area of the thorax during exercise, with a significantly higher SR on the neck. The SR measured on the thorax by direct sweat collection and by dew-point hygrometry were of similar magnitude. Mean whole body SR calculated from total body water loss was not significantly different from mean whole body SR estimated from direct sweat collection or dew-point hygrometry measurements on the thorax.

Conclusions

Dew-point hygrometry and direct sweat collection are useful methods for determination of local SR in horses during prolonged, steady-state exercise in moderate ambient conditions. Both methods of local SR determination provide an accurate estimate of whole body SR. (Am J Vet Res 1997;58:175–181)

Free access
in American Journal of Veterinary Research

Summary

Hemorheologic alterations induced by incremental treadmill exercise were examined in 5 Thoroughbreds. Blood viscosity; pcv; rbc filterability, density gradient profile, and shape; serum and rbc electrolyte concentrations; and plasma total solids and lactate concentrations were measured before exercise, at treadmill speeds of 9 and 13 m/s, and 10 minutes after exercise. Exercise was associated with significant (P < 0.05) increases in pcv, blood viscosity, and plasma total solids concentration. After adjustment of pcv to 40% by adding or removing each horse's own plasma, blood viscosity remained significantly greater in the sample obtained at 13 m/s, compared with that in samples taken at rest. Filterability of rbc was significantly decreased at 13 m/s, compared with values from other sampling times. During exercise, a significantly greater proportion of the rbc were less dense and were found in the upper layers of the rbc density gradient profile, compared with resting values. This change was associated with a significant increase in rbc mean cell volume. Rapid increases in serum sodium and potassium concentrations during exercise were accompanied by significant increases in rbc potassium and chloride concentrations. This study revealed a consistent pattern of hemorheologic alterations associated with exercise in Thoroughbreds, suggesting that multiple hemorheologic tests are needed to adequately define these complex alterations during exercise in horses.

Free access
in American Journal of Veterinary Research