Effects of long-term oral administration of levothyroxine sodium on glucose dynamics in healthy adult horses

OBJECTIVE: To determine the effects of long-term oral administration of levothyroxine sodium (L-T(4)) on glucose dynamics in adult euthyroid horses. ANIMALS: 6 healthy adult mares. PROCEDURES: Horses received L-T(4) (48 mg/d) orally for 48 weeks. Frequently sampled IV glucose tolerance test procedures were performed on 3 occasions (24-hour intervals) before and at 16, 32, and 48 weeks during the treatment period. Data were assessed via minimal model analysis. The repeatability of measurements was evaluated. RESULTS: During treatment, body weight decreased significantly from the pretreatment value; mean +/- SD weight was 49 +/- 14 kg, 43 +/- 7 kg, and 25 +/- 18 kg less than the pretreatment value at weeks 16, 32, and 48, respectively. Compared with pretreatment findings, 1.8-, 2.4-, and 1.9-fold increases in mean insulin sensitivity (SI) were detected at weeks 16, 32, and 48, respectively; SI was negatively correlated with body weight (r = -0.42; P < 0.001). During treatment, glucose effectiveness increased and the acute insulin response to glucose decreased. Overall mean within-horse coefficients of variation were 5% and 29% for plasma glucose and serum insulin concentrations, respectively, and 33%, 26%, and 23% for SI, glucose effectiveness, and the acute insulin response to glucose, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Long-term administration of L-T(4) was associated with weight loss and increased SI in adult euthyroid horses, although other factors may have confounded results. Levothyroxine sodium may be useful for the treatment of obesity and insulin resistance in horses, but further studies are required.     

Effect of hypothyroidism on blood lipid concentrations in horses.

OBJECTIVE: To measure and compare concentrations of selected blood lipids before and after thyroidectomy in horses. ANIMALS: 5 healthy adult mares. PROCEDURE: Mares were confirmed to be euthyroid. Thyroidectomy was performed, and hypothyroidism was confirmed. Selected blood lipid variables were measured before hypothyroidism was induced and weekly for 4 weeks after induction. Plasma concentrations of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), serum triglyceride (TG), total cholesterol (TC), and nonesterified fatty acid (NEFA) were measured. The composition of VLDL and LDL also was examined. RESULTS: Mean plasma concentrations of VLDL and LDL increased significantly after thyroidectomy. By 4 weeks after thyroidectomy, a ninefold increase in mean plasma concentration of VLDL and a threefold increase in LDL, compared with baseline values, were detected. After thyroidectomy, mean percentage of TG in VLDL increased significantly, whereas free cholesterol and cholesterol ester content decreased. Mean percentage of TG in LDL also increased by 3 to 4 weeks after thyroidectomy. Serum concentrations of TG and TC increased, whereas serum NEFA concentration decreased. CONCLUSIONS: Hypothyroidism significantly alters blood lipid concentrations of horses. After thyroidectomy, markedly high VLDL concentration, appearance of TG-rich VLDL, increased serum concentrations of TG and TC, and decreased blood concentration of NEFA were evident. CLINICAL RELEVANCE: Examination of blood lipid concentrations of horses may be useful for detecting naturally acquired hypothyroidism.     

Effects of hypothyroidism and withholding of feed on plasma lipid concentrations,concentration and composition of very-low-density lipoprotein,and plasma lipase activity in horses

OBJECTIVE: To evaluate selected concentrations of blood lipids and lipase activities in euthyroid and hypothyroid horses deprived of feed for 96 hours. ANIMALS: 4 healthy adult mares and 4 thyroidectomized adult mares. PROCEDURE: Horses were deprived of feed for 96 hours. Blood samples were collected at 24-hour intervals and analyzed to determine concentrations of non-esterified fatty acid (NEFA), triglyceride (TG), total cholesterol (TC), and very-low-density lipoprotein (VLDL) as well as composition of VLDL. Plasma lipase activities were measured after feed was withheld for 96 hours and 12 days after resumption of feeding. RESULTS: Time significantly affected plasma NEFA, VLDL, TG, and TC concentrations in both groups of horses. During the 96-hour period, mean plasma concentrations of NEFA and VLDL increased 10-fold in euthyroid horses and increased 5-fold and 9-fold, respectively, in hypothyroid horses. Mean plasma TG concentrations increased 8-fold in both groups, and plasma TC concentrations significantly increased by 33 and 30%, respectively. Composition of VLDL was significantly affected by feed deprivation in euthyroid horses. Activities of lipoprotein lipase and hepatic lipase were significantly higher in feed-deprived horses. Activity of hepatic lipase was significantly lower in hypothyroid horses than in euthyroid horses. CONCLUSIONS AND CLINICAL RELEVANCE: Hypothyroidism did not significantly alter the magnitude of the response of blood lipids to feed deprivation. Thyroid hormones may reduce variability in blood lipid concentrations but do not determine susceptibility to hyperlipemia. Hypothyroidism does not appear to be a factor in the pathogenesis of hyperlipemia in horses.     

Effects of oral administration of levothyroxine sodium on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone in healthy adult mares

OBJECTIVE: To determine the effects of levothyroxine sodium (L-T4) on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone (TRH) in euthyroid horses. ANIMALS: 12 healthy adult mares. PROCEDURE: 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provided for 2 weeks. Four additional horses remained untreated. Serum concentrations of total triiodothyronine (tT3), total thyroxine (tT4), free T3 (fT3), free T4 (fT4), and thyroid-stimulating hormone (TSH) were measured in samples obtained at weeks 0, 2, 4, 6, and 8; 1.2 mg of TRH was then administered i.v., and serum concentrations of thyroid gland hormones were measured 2 and 4 hours after injection. Serum reverseT3 (rT3) concentration was also measured in the samples collected at weeks 0 and 8. RESULTS: Treated horses lost a significant amount of weight (median, 19 kg). Significant treatment-by-time effects were detected for serum tT3, tT4, fT3, fT4, and TSH concentrations, and serum tT4 concentrations were positively correlated (r, 0.95) with time (and therefore dosage) in treated horses. Mean +/- SD serum rT3 concentration significantly increased in treated horses (3.06 +/- 0.51 nmol/L for week 8 vs 0.74 +/- 0.22 nmol/L for week 0). Serum tT3, tT4, fT3, and TSH concentrations in response to TRH injections differed significantly between treated and untreated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of levothyroxine sodium increased serum tT4 concentrations and blunted responses toTRH injection in healthy euthyroid horses.     

Effect of withholding feed on concentration and composition of plasma very low density lipoprotein and serum nonesterified fatty acids in horses

OBJECTIVE: To measure and compare the concentration and composition of very low-density lipoprotein (VLDL) in plasma and selected lipids in serum of horses fed mixed grass hay ad libitum or denied feed for 36 hours. ANIMALS: 4 healthy adult mares. PROCEDURE: Mares were either fed mixed grass hay ad libitum or denied feed for 36 hours beginning at 8:00 AM. Blood samples were collected every 2 hours during the study period and analyzed for nonesterified fatty acid (NEFA), triglyceride (TG), VLDL, and glucose concentrations and composition of VLDL. RESULTS: Withholding feed significantly increased mean serum concentrations of NEFA. By 36 hours, a 16-fold increase in mean serum NEFA concentration and 2-fold increase in mean plasma VLDL concentration, compared with baseline values, were detected. Mean plasma TG concentrations significantly increased with time in feed-deprived horses. Significantly lower overall mean plasma glucose concentrations were detected in feed-deprived horses. Mean percentage of protein in VLDL was significantly lower in feed-deprived horses. Plasma VLDL concentrations varied widely among horses in response to withholding feed. Plasma TG and VLDL concentrations remained unaltered in 2 horses. CONCLUSIONS AND CLINICAL RELEVANCE: Withholding feed significantly increases blood lipid concentrations in horses, but individual horses respond differently. Serum NEFA concentrations were increased in all 4 horses denied feed, indicating mobilization of tissue triglyceride stores. Variation in plasma VLDL concentration in response to withholding feed suggests that its metabolism is strongly influenced by other, as yet undetermined, factors in horses. Differences in the plasma VLDL concentrations among horses in response to withholding feed may be used as an indication of susceptibility to the hyperlipemic syndrome of Equidae.     

Effects of rice bran oil on plasma lipid concentrations, lipoprotein composition, and glucose dynamics in mares

Plasma lipid concentrations, lipoprotein composition, and glucose dynamics were measured and compared between mares fed diets containing added water, corn oil (CO), refined rice bran oil (RR), or crude rice bran oil (CR) to test the hypothesis that rice bran oil lowers plasma lipid concentrations, alters lipoprotein composition, and improves insulin sensitivity in mares. Eight healthy adult mares received a basal diet fed at 1.5 times the DE requirement for maintenance and each of the four treatments according to a repeated 4 x 4 Latin square design consisting of four 5-wk feeding periods. Blood samples were collected for lipid analysis after mares were deprived of feed overnight at 0 and 5 wk. Glucose dynamics were assessed at 0 and 4 wk in fed mares by combined intravenous glucose-insulin tolerance tests. Plasma glucose and insulin concentrations were measured, and estimated values of insulin sensitivity (SI), glucose effectiveness, and net insulin response were obtained using the minimal model. Mean BW increased (P = 0.014) by 29 kg (range = 10 to 50 kg) over 5 wk. Mean plasma concentrations of NEFA, triglyceride (TG), and very low-density lipoprotein (VLDL) decreased (P < 0.001) by 55, 30, and 39%, respectively, and plasma high-density lipoprotein and total cholesterol (TC) concentrations increased (P < 0.001) by 15 and 12%, respectively, over 5 wk. Changes in plasma NEFA (r = 0.58; P < 0.001) and TC (r = 0.44; P = 0.013) concentrations were positively correlated with weight gain over 5 wk. Lipid components of VLDL decreased (P < 0.001) in abundance over 5 wk, whereas the relative protein content of VLDL increased by 39% (P < 0.001). Addition of oil to the basal diet instead of water lowered plasma NEFA and TG concentrations further (P = 0.002 and 0.020, respectively) and increased plasma TC concentrations by a greater magnitude (P = 0.072). However, only plasma TG concentrations and VLDL free cholesterol content were affected (P = 0.024 and 0.009, respectively) by the type of oil added to the diet. Mean plasma TG concentration decreased by 14.2 mg/dL over 5 wk in the CR group, which was a larger (P < 0.05) decrease than the one (-5.3 mg/dL) detected in mares that received water. Consumption of experimental diets lowered S(I), but glucose dynamics were not affected by oil supplementation. Addition of oil to the diet altered blood lipid concentrations, and supplementation with CR instead of water specifically affected plasma TG concentrations and VLDL free cholesterol content.     

Effects of long-term oral administration of levothyroxine sodium on serum thyroid hormone concentrations, clinicopathologic variables, and echocardiographic measurements in healthy adult horses

OBJECTIVE: To determine the effects of long-term oral levothyroxine sodium (L-T(4)) administration on serum thyroid hormone concentrations, thyroid gland function, clinicopathologic variables, and echocardiographic examination measurements in adult euthyroid horses. ANIMALS: 6 healthy adult mares. PROCEDURES: Horses received L-T(4) (48 mg/d) orally for 48 weeks. Every 4 weeks, physical examinations were performed; blood samples were collected for CBC, plasma biochemical analyses, and assessments of serum total triiodothyronine (tT(3)) and thyroxine (tT(4)) concentrations. Plasma creatine kinase MB activity and cardiac troponin I concentration were also measured. Echocardiographic examinations were performed before and at 16, 32, and 48 weeks during the treatment period. RESULTS: During the treatment period, mean body weight decreased significantly; heart rate varied significantly, but the pattern of variation was not consistent. Significant time effects were detected for certain clinicopathologic variables, but mean values remained within reference ranges. Cardiac troponin I was only detectable in 8 of 24 plasma samples (concentration range, 0.01 to 0.03 ng/mL). Serum creatine kinase MB activity did not change significantly over time. Compared with the pretreatment value, 5.4-, 4.0-, and 3.7-fold increases in mean serum tT(4) concentrations were detected at 16, 32, and 48 weeks, respectively. Some cardiac measurements changed significantly over time, but mean values remained within published reference ranges. Mean fractional shortening was lower than the pretreatment mean value at 16 and 32 weeks. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, long-term oral administration of 48 mg of L-T(4)/d significantly increased serum tT(4) concentrations and did not appear to adversely affect health.     

Effects of a supplement containing chromium and magnesium on morphometric measurements, resting glucose, insulin concentrations and insulin sensitivity in laminitic obese horses

Reasons for performing study: Obesity and insulin resistance are risk factors for laminitis in equids and supplements containing chromium and magnesium might improve insulin sensitivity. Hypothesis: A supplement containing chromium, magnesium and other nutraceuticals would alter morphometric measurements, blood variables, and insulin sensitivity in laminitic obese horses. Methods: Twelve previously laminitic obese (body condition score ≥ 7/9) horses were randomly allocated to treatment (n = 6) and control (n = 6) groups and 2 obese horses with clinical laminitis were included in the treatment group. Treated animals received 56 g supplement with 0.25 kg oats once daily for 16 weeks. The supplement contained chromium (5 mg/day as yeast), magnesium (8.8 g/day as oxide/proteinate), and other nutraceuticals. Insulin‐modified frequently sampled i.v. glucose tolerance tests were performed with hay provided at 0, 8 and 16 weeks, and insulin sensitivity was estimated by minimal model analysis. Physical measurements were collected at the same points. Horses were not exercised. Results: Hyperinsulinaemia (>30 µu/ml) was detected in 12 of 14 horses prior to treatment. Glucose and insulin data from one mare with clinical laminitis were excluded because of persistent pain. Mean ± s.d. insulin sensitivity was 0.64 ± 0.62 × 10^?4 l/min/mu prior to treatment for the remaining 13 horses. Time and treatment × time effects were not significant for any of the variables examined, with the exception of resting insulin concentrations, which significantly increased over time (P = 0.018). Health status remained the same. Conclusions: The supplement containing chromium and magnesium evaluated in this study did not alter morphometric measurements, blood variables, resting insulin concentrations or insulin sensitivity in laminitic obese horses. Potential relevance: Additional research is required to determine the appropriate use of chromium and magnesium supplements in horses.     

Comparison of Three Methods for Evaluation of Equine Insulin Regulation in Horses of Varied Body Condition Score

Multiple dynamic field tests are used for assessment of equine insulin resistance or altered insulin regulation. However, the relationship between markers of glucose homeostasis and insulin disposal obtained by different testing protocols is unknown. We hypothesized that two recently developed field tests for evaluation of equine insulin dysregulation, the insulin response to dexamethasone test (IRDT) and oral sugar test (OST), would yield comparable results to the hyperinsulinemic euglycemic clamp (HEC). Fifteen light breed horses with body condition scores (BCS) 3 of 9 to 8 of 9 were used in this study. Eight horses (BCS, 5 of 9 to 7 of 9) underwent an OST under two different housing conditions, pasture, and stall (experiment 1). These eight horses also underwent an HEC and IRDT over a 4-week period (experiment 2), and results were compared with the OST stall. Finally, eight horses (BCS, 3 of 9 to 8 of 9), including one horse from experiments 1 and 2, underwent an OST on pasture three times over a 14–16-week period during the summer and the fall (experiment 3). The HEC did not correlate with either the OST or IRDT. The OST was not different when performed in the pasture compared within a stall but did change significantly over time on pasture. These results suggest that in insulin-sensitive horses, the OST and IRDT results are not primarily determined by tissue insulin sensitivity in horses of varying BCS. Furthermore, OST results may vary depending on pasture composition or season.     

Use of proxies and reference quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses

OBJECTIVE: To develop proxies calculated from basal plasma glucose and insulin concentrations that predict insulin sensitivity (SI; L.min(-1) x mU(-1)) and beta-cell responsiveness (ie, acute insulin response to glucose [AIRg]; mU/L x min(-1)) and to determine reference quintiles for these and minimal model variables. ANIMALS: 1 laminitic pony and 46 healthy horses. PROCEDURE: Basal plasma glucose (mg/dL) and insulin (mU/L) concentrations were determined from blood samples obtained between 8:00 AM and 9:00 AM. Minimal model results for 46 horses were compared by equivalence testing with proxies for screening SI and pancreatic beta-cell responsiveness in humans and with 2 new proxies for screening in horses (ie, reciprocal of the square root of insulin [RISQI] and modified insulin-to-glucose ratio [MIRG]). RESULTS: Best predictors of SI and AIRg were RISQI (r = 0.77) and MIRG (r = 0.75) as follows: SI = 7.93(RISQI) - 1.03 and AIRg = 70.1(MIRG) - 13.8, where RISQI equals plasma insulin concentration(-0.5) and MIRG equals [800 - 0.30(plasma insulin concentration 50)(2)]/(plasma glucose concentration - 30). Total predictive powers were 78% and 80% for RISQI and MIRG, respectively. Reference ranges and quintiles for a population of healthy horses were calculated nonparametrically. CONCLUSIONS AND CLINICAL RELEVANCE: Proxies for screening SI and pancreatic beta-cell responsiveness in horses from this study compared favorably with proxies used effectively for humans. Combined use of RISQI and MIRG will enable differentiation between compensated and uncompensated insulin resistance. The sample size of our study allowed for determination of sound reference range values and quintiles for healthy horses.     

Changes in lipoprotein composition in horses fed a fat-supplemented diet

This study was designed to compare the effects of a fat-supplemented diet versus a traditional diet on the lipoprotein (LP) content in horses. In the first of two trials, eight two-year old horses were fed a basal diet, in which 80% of the digestible energy was supplied as chopped alfalfa hay. One group of four horses (fat-supplemented group, FS) was fed the remaining 20% of the digestible energy as corn oil, while the other group of four horses (control) was fed rolled corn to complete their diet. Blood samples were collected at the start of the experiment and every 2.5 weeks thereafter for 10 weeks. Total serum lipids were measured in both groups of horses and the lipoproteins were fractionated into very low density LP (VLDL), low density LP (LDL), and high density LP (HDL) using ultracentrifugation and agarose-column chromatography. Each LP fraction was measured for protein, cholesterol (CH) and triglyceride TG) content. Total serum lipids were increased in the FS group above the control (9.16 vs. 4.65 mg/ml, week 5). Serum cholesterol and triglyceride concentrations were elevated in the FS group, but were highly variable. Variations in lipid concentrations may have been due to variation in time of sampling during the day. In the second trial, four of the eight horses were used and divided into the same two groups; FS vs. control. After an initial sample, postprandial serial blood samples (1 hour intervals for 8 hours) were drawn at 2, 4 and 6 weeks. Upon examination of the data, Hour 3 post-feeding was chosen to represent postprandial LP values. In both trials, the horses were able to adapt to the added dietary fat. Maintenance of body weight and increased speed of lipid clearance from the blood by the end of each trial in the FS group support this statement. In the FS group, there was an increase in VLDL TG concentration, but not in LDL. This indicates an increase in VLDL TG clearance from the circulation, presumably by increased lipoprotein lipase (LPL) activity. Cholesterol concentrations were also increased in the FS horses in the LDL and HDL. The rise in cholesterol may be attributed to endogenous recycling of liver products such as bile salts, which aid in digestion and absorption and are cholesterol based. In addition, there were greater quantities of LDL and HOL produced in the FS horses as supported by the increased protein concentrations as well as larger peaks for the eluate from the gel filtration column.     

Clinical Evaluation of a Novel Liquid Formulation of L-Thyroxine for Once Daily Treatment of Dogs with Hypothyroidism

Background: A liquid solution of levothyroxine (L-T4) is available for treatment of canine hypothyroidism.
Hypothesis: Once daily oral administration of a liquid L-T4 solution is effective and safe for controlling hypothyroidism in dogs.
Animals: Thirty-five dogs with naturally occurring hypothyroidism.
Methods: Dogs received L-T4 solution PO once daily at a starting dosage of 20 μg/kg body weight (BW). The dose was adjusted every 4 weeks, based on clinical signs and peak serum total T4 (tT4) concentrations. Target peak serum tT4 and thyroid stimulating hormone (TSH) concentrations, 4–6 hours posttreatment, were 35–95 nmol/L and < 0.68 ng/mL, respectively. Dogs were followed for up to 22 weeks after establishment of the maintenance dose.
Results: Clinical signs of hypothyroidism improved or resolved in 91% of dogs after 4 weeks of L-T4 treatment at 20 μg/kg once daily. The maintenance dose was established in 76, 94, and 100% of dogs after 4, 8, and 12 weeks of treatment, respectively. This was 20 μg L-T4/kg BW for 79% of the dogs, 30 μg/kg BW for 15%, and 10–15 μg/kg BW in the remaining 6%, once daily. Thereafter, median peak tT4 and TSH concentrations were 51 nmol/L and 0.18 ng/mL, respectively, and remained stable during the 22-week follow-up; clinical signs did not recur.
Conclusions and Clinical Importance: All of the hypothyroid dogs had rapid clinical and hormonal responses to supplementation with the PO-administered L-T4 solution. The starting dosage of 20 μg L-T4/kg BW once daily was suitable for 79% of dogs.     

Randomized, controlled study of inhaled fluticasone propionate, oral administration of prednisone, and environmental management of horses with recurrent airway obstruction

OBJECTIVE: To determine whether administration of glucocorticoids provides additional benefits to environmental management of horses with recurrent airway obstruction (RAO). ANIMALS: 28 horses with RAO. PROCEDURE: Horses were classified as having mild, moderate, or severe RAO. Within each category, horses were randomly assigned to receive inhaled fluticasone propionate, inhaled control substance, or oral administration of prednisone. During the 4-week study, horses were maintained outdoors and fed a pelleted feed. Clinical scores, pulmonary function, results of cytologic examination of bronchoalveolar lavage fluid (BALF), and adrenal gland function were determined before and 2 and 4 weeks after initiation of treatment. RESULTS: Clinical score and pulmonary function of all RAO-affected horses improved during the treatment period. After 4 weeks, clinical scores and pulmonary function of horses treated with a glucocorticoid were not different from those for the control treatment. In horses with severe RAO, treatment with fluticasone for 2 weeks resulted in significantly greater improvement in pulmonary function, compared with pulmonary function after treatment with prednisone or the control substance. Treatment with a glucocorticoid for 4 weeks and a low-dust environment did not have any effect on cellular content of BALF Treatment with prednisone for 2 weeks resulted in a significant decrease in serum cortisol concentration, compared with concentrations after administration of fluticasone or the control substance. CONCLUSIONS AND CLINICAL RELEVANCE: Environmental management is the most important factor in the treatment of horses with RAO. Early treatment with inhaled fluticasone can help accelerate recovery of horses with severe RAO.     

Effects of short- and long-term recombinant equine growth hormone and short-term hydrocortisone administration on tissue sensitivity to insulin in horses

OBJECTIVE: To determine the effects of short-term IV administration of hydrocortisone or equine growth hormone (eGH) or long-term IM administration of eGH to horses on tissue sensitivity to exogenous insulin. ANIMALS: 5 Standardbreds and 4 Dutch Warmblood horses. PROCEDURE: The euglycemic-hyperinsulinemic clamp technique was used to examine sensitivity of peripheral tissues to exogenous insulin 24 hours after administration of a single dose of hydrocortisone (0.06 mg/kg), eGH (20 microg/kg), or saline (0.9% NaCl) solution and after long-term administration (11 to 15 days) of eGH to horses. The amounts of metabolized glucose (M) and plasma insulin concentration (I) were determined. RESULTS: Values for M and the M-to-I ratio were significantly higher 24 hours after administration of a single dose of hydrocortisone than after single-dose administration of eGH or saline solution. After long-term administration of eGH, basal I concentration was increased and the mean M-to-I ratio was 22% lower, compared with values for horses treated with saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Increases in M and the M-to-I ratio after a single dose of hydrocortisone imply that short-term hydrocortisone treatment increases glucose use by, and insulin sensitivity of, peripheral tissues. Assuming a single dose of hydrocortisone improves sensitivity of peripheral tissues to insulin, it may be an interesting candidate for use in reducing insulin resistance in peripheral tissues of horses with several disease states. In contrast, long-term administration of eGH decreased tissue sensitivity to exogenous insulin associated with hyperinsulinemia. Therefore, increased concentrations of growth hormone may contribute to insulin resistance in horses with various disease states.     

Serial alterations in digital hemodynamics and endothelin-1 immunoreactivity, platelet-neutrophil aggregation, and concentrations of nitric oxide, insulin, and glucose in blood obtained from horses following carbohydrate overload

OBJECTIVE: To quantify changes in endothelium-derived factors and relate those changes to various aspects of digital hemodynamics during the prodromal stages of carbohydrate overload (CHO)-induced laminitis in horses. ANIMALS: 20 adult horses without abnormalities of the digit. PROCEDURES: Digital and jugular venous blood samples were collected at 1-hour intervals (for assessment of endothelin-1 [ET-1] immunoreactivity and measurement of glucose, insulin, and nitric oxide [NO] concentrations) or 4-hour intervals (CBC and platelet-neutrophil aggregate assessment) for 8 hours or 16 hours after induction of CHO-associated laminitis in horses treated with an ET-1 antagonist. Effects of treatment, collection site, and time and the random effects of horse on each variable were analyzed by use of a repeated-measures model. Where treatment and collection site had no significant effect, data were combined. RESULTS: Compared with baseline values, CHO resulted in changes in several variables, including a significant increase from baseline in digital blood ET-like immunoreactivity at 11 hours; digital blood ET-like immunoreactivity was significantly greater than that in jugular venous blood at 8, 9, 11, and 12 hours. Digital and jugular venous blood concentrations of glucose increased from baseline significantly at 3, 4, and 5 hours; insulin concentration increased significantly at 5 hours; and the number of platelet-neutrophil aggregates increased significantly at 12 hours. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, concurrent increases in venous blood ET-1 immunoreactivity, insulin and glucose concentrations, and platelet-neutrophil aggregates support a role of endothelial dysfunction in the pathogenesis of CHO-induced laminitis.     

Tissue strength and wound morphology of the equine linea alba after ventral median celiotomy

OBJECTIVE: To evaluate the tensile strength and wound morphology of the equine linea alba at intervals over 6 months after ventral median celiotomy. STUDY DESIGN: Linea alba tensile strength and wound morphology were determined at 2, 4, 8, 16, and 24 weeks postoperatively. Linea alba samples from 3 unoperated horses were used as controls. ANIMALS: Eighteen adult horses, weighing 400 to 500 kg, 4 to 15 years old. METHODS: Tensile strength and thickness of incised linea alba samples collected at 2, 4, 8, 16, and 24 weeks after ventral median celiotomy were compared with control linea alba samples. Additional samples were subjectively evaluated for wound morphology, notably collagen morphology. RESULTS: Control linea alba had a mean (+/-SEM) tensile strength of 484.9 +/- 58.3 N and was significantly (P < or = .05) stronger than at 2 weeks (87.7 +/- 61.4 N) after surgery. The tensile strength of 4-week (305.8 +/- 61.7 N), 8-week (465.4 +/- 56.5 N), and 16-week (477.8 +/- 57.2 N) samples were not significantly different from control linea alba. At 24 weeks, the tensile strength (721.0 +/- 57.9 N) was significantly stronger than control. The 2-, 4-, and 8-week samples were significantly thicker than controls, whereas the 16- and 24-week samples were not different from controls. On microscopy, control samples were characterized by dense mature collagen bundles. At 2 weeks, samples consisted primarily of granulation tissue, whereas at 4 weeks, samples had immature collagen fibers that were not formed into bundles, and at 8, 16, and 24 weeks, all samples had abundant mature collagen fibers formed into bundles. CONCLUSIONS: At 8 weeks, incised and sutured equine linea alba had a tensile strength comparable with non-incised linea alba and was characterized by mature collagen. CLINICAL RELEVANCE: Based on tensile strength and wound morphology, horses that have had an uncomplicated recovery after ventral median celiotomy should be able to return to controlled exercise as early as 60 days after surgery.     

Serum creatine kinase response to exercise during dexamethasone-induced insulin resistance in Quarter Horses with polysaccharide storage myopathy

OBJECTIVE: To determine effects of dexamethasone on insulin sensitivity, serum creatine kinase (CK) activity 4 hours after exercise, and muscle glycogen concentration in Quarter Horses with polysaccharide storage myopathy (PSSM). ANIMALS: 4 adult Quarter Horses with PSSM. PROCEDURE: A 2 x 2 crossover design was used with dexamethasone (0.08 mg/kg) or saline (0.9% NaCl) solution administered IV every 48 hours. Horses were exercised on a treadmill daily for 3 wk/treatment with a 2-week washout period between treatments. Serum CK activity was measured daily 4 hours after exercise. At the end of each treatment period, serum cortisol concentrations were measured, a hyperinsulinemic euglycemic clamp (HEC) technique was performed, and muscle glycogen content was determined. RESULTS: Mean +/- SEM serum cortisol concentration was significantly lower after 48 hours for the dexamethasone treatment (0.38 +/- 0.08 mg/dL), compared with the saline treatment (4.15 +/- 0.40 mg/dL). Dexamethasone significantly decreased the rate of glucose infusion necessary to maintain euglycemia during the HEC technique, compared with the saline treatment. Muscle glycogen concentrations and mean CK activity after exercise were not altered by dexamethasone treatment, compared with the saline treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Dexamethasone significantly reduced whole-body insulin-stimulated glucose uptake in Quarter Horses with PSSM after a 3-week period but did not diminish serum CK response to exercise or muscle glycogen concentrations in these 4 horses. Therefore, a decrease in glucose uptake for 3 weeks did not appear to alleviate exertional rhabdomyolysis in these horses. It is possible that long-term treatment may yield other results.     

Effects of trimethoprim-sulfadiazine on tear production and the fluctuations of Schirmer tear test values in horses

The objectives of this study were to observe the effects of trimethoprim-sulfadiazine on equine tear production and to determine normal fluctuations in Schirmer tear test (STT) values in horses. A randomized, placebo-controlled, blinded clinical trial measuring STT values in 15 horses over an 8-week period was performed. The treatment group (eight horses) received 30 mg/kg trimethoprim-sulfadiazine orally once a day and the control group (seven horses) received placebo (flour) at the same time. All horses were housed outdoors throughout the study. Schirmer tear test values were measured at 0, 2, 4, 6 and 8 weeks, and 4 weeks after discontinuation of treatment. There were no significant differences in tear production between the treated and control groups. Fluctuations in STT were observed and may result from individual and environmental variations. Trimethoprim-sulfadiazine did not decrease tear production in the horses in this study. Horses normally experience periodic fluctuations in STT values.     

Glucose uptake in horses with polysaccharide storage myopathy

OBJECTIVE: To determine whether excessive glycogen accumulation in skeletal muscle of Quarter Horses with polysaccharide storage myopathy (PSSM) is a result of enhanced cellular uptake of glucose. ANIMALS: 6 horses with PSSM and 10 healthy (control) horses. PROCEDURE: Intravenous glucose tolerance tests (IVGTT), oral glucose tolerance tests (OGTT), and modified insulin tolerance tests (MITT) were performed. Plasma glucose and insulin concentrations were measured in blood samples collected before and for up to 8 hours after glucose or insulin administration. RESULTS: Peak glucose concentrations during IVGTT were similar for both groups of horses, but rate of glucose clearance was 1.5 times faster in horses with PSSM than in controls. Moreover, circulating concentrations of insulin before and after glucose injection were lower in the PSSM group. Blood glucose concentrations from minute 90 to minute 300 of the OGTT were lower in horses with PSSM than in controls. The MITT resulted in acute decreases in blood glucose concentrations in both groups of horses; however, horses with PSSM sustained low blood glucose concentrations for more than 3 hours after insulin injection, whereas blood glucose concentrations in controls returned to baseline values within 2 hours. CONCLUSIONS: Quarter Horses with PSSM have enhanced cellular uptake of glucose that may be, in part, caused by an increased sensitivity to insulin. CLINICAL RELEVANCE: Horses with PSSM have an increased rate of glucose clearance in response to insulin secretion. Thus, diets low in soluble carbohydrate may be the most effective way to decrease glycogen accumulation in skeletal muscle of these horses.