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- Author or Editor: Nicholas Frank x
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Abstract
Objective—To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis.
Animals—12 healthy adult horses (10 mares and 2 geldings).
Procedures—Horses were randomly assigned to receive LPS (total dose, 80 μg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 μg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammatory cytokine gene expression was determined for blood samples obtained every 8 hours, and IV glucose tolerance tests were performed.
Results—All LPS-treated horses had signs of depression and mild colic; those signs abated as the study progressed. Administration of LPS increased expression of interleukin-1β, interleukin-6, and interleukin-8, but results were not significantly different between LPS treatment groups. Cytokine expression was significantly higher on the first day versus the second day of LPS treatment. Interleukin-1β expression was positively correlated with rectal temperature and expression of other cytokines. Glucose and insulin dynamics for both LPS groups combined did not differ significantly from those of the saline solution group. Signs of laminitis were not detected in any of the horses.
Conclusions and Clinical Relevance—Horses developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses.
Abstract
Objective—To assess antiulcerogenic properties of 3 dietary oils.
Animals—8 healthy adult mares.
Procedure—A protocol to induce gastric ulcers was used and included 240 mL of water plus corn oil, refined rice bran oil, or crude rice bran oil administered each day for 6 weeks according to a 4 × 4 Latin square randomized crossover design with 5-week washout intervals. A 7-day alternating feed deprivation period was included between weeks 5 and 6. Omeprazole was administered daily for the last 14 days of each washout interval. Endoscopic examinations of the stomach were performed at 0, 5, and 6 weeks, and the number (0 to 4 scale) and severity (0 to 5 scale) of ulcers were scored. Gastric fluid was collected at 0 and 5 weeks.
Results—Median body weight significantly increased by 29 kg (range, 10 to 50 kg). Mean ± SE gastric fluid pH significantly decreased from 4.9 ± 0.4 to 3.1 ± 0.3 over 5 weeks, and total volatile fatty acid concentration significantly decreased over time. Mean ± SE severity of nonglandular ulcers significantly increased from 0.4 ± 0.1 to 1.2 ± 0.2 over 5 weeks. Nonglandular ulcers significantly increased in number (mean ± SE, 1.3 ± 0.2 to 3.0 ± 0.2) and severity (mean ± SE, 1.2 ± 0.2 to 2.6 ± 0.2) during the 7-day alternating feed deprivation period. No effects of treatment were detected.
Conclusions and Clinical Relevance—In this model dietary oils did not prevent gastric ulcers from forming in the nonglandular portion of the stomach of horses. (Am J Vet Res 2005;66:2006–2011)
Abstract
Objective—To determine the effects of long-term oral levothyroxine sodium (L-T4) 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-T4 (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 (tT3) and thyroxine (tT4) 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 tT4 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-T4/d significantly increased serum tT4 concentrations and did not appear to adversely affect health.
Abstract
Objective—To determine the effects of long-term oral administration of levothyroxine sodium (L-T4) on glucose dynamics in adult euthyroid horses.
Animals—6 healthy adult mares.
Procedures—Horses received L-T4 (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-T4 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.
Abstract
OBJECTIVE To determine whether plasma ACTH concentrations vary following administration of a thyrotropin-releasing hormone (TRH) solution prepared for research purposes and stored at −20°C (rTRH) or prepared by a compounding pharmacy and stored at room temperature (approx 22°C; cTRH).
ANIMALS 34 adult horses.
PROCEDURES The study consisted of 2 experiments. In experiment 1, each horse underwent 2 TRH stimulation tests separated by 24 hours; 10 horses were administered cTRH for the first test and rTRH for the second test (group 1), 10 horses were administered rTRH for the first test and cTRH for the second test (group 2), and 10 horses were administered rTRH for both tests (group 3). Plasma ACTH concentrations were measured at 0 (baseline) and 30 minutes after TRH administration and the delta ACTH responses (change in ACTH concentration after TRH administration) were calculated. In experiment 2, the design was the same as that for experiment 1 except there were 14 days between tests, ACTH was measured at 0 and 10 minutes after TRH administration, and 11, 9, and 10 horses were assigned to groups 1, 2, and 3, respectively.
RESULTS Adverse effects associated with TRH administration included transient coughing and yawning. In experiment 1, the median delta ACTH response for the second test was significantly lower than that for the first test for all groups. In experiment 2, the median delta ACTH response did not differ significantly between the first and second tests for any group, ACTH concentrations after rTRH administration were positively correlated (r s = 0.95) with those after cTRH administration, and the mean ± SD bias in post-TRH ACTH concentration between rTRH and cTRH was 2.9 ± 12.4 pg/mL.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the TRH stimulation test should not be repeated within 24 hours, and cTRH solution stored at room temperature could be used to effectively perform TRH stimulation testing in horses.
Abstract
Objective—To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS).
Animals—6 healthy horses and 6 horses with EMS.
Procedures—Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion.
Results—Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The magnitude of blood cytokine responses did not differ between groups, but increased expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α persisted for longer periods in EMS-affected horses. Lipopolysaccharide infusion increased liver tissue gene expressions of IL-6 in healthy horses and IL-8 in both healthy and EMS-affected horses, but these gene expressions did not differ between groups.
Conclusions and Clinical Relevance—Results supported the hypothesis that EMS affects horses’ inflammatory responses to endotoxin by prolonging cytokine expression in circulating leukocytes. These findings are relevant to the association between obesity and laminitis in horses with EMS.
Abstract
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. (Am J Vet Res 2002;63:1018–1021)
Abstract
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 nonesterified 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. (Am J Vet Res 2003;64:823–828)
Abstract
Objective—To ascertain whether laminitis can be induced via administration of oligofructose (OF) at doses of 5.0 and 7.5 g/kg in horses and to assess glucose and insulin dynamics before and after treatment.
Animals—19 adult horses.
Procedures—Horses were fed OF (1.0 g/kg) mixed with oats for 6 days. Oligofructose at doses of 5.0 and 7.5 g/kg was then mixed with 4 L of water and administered (0 hours) to 8 (group A) and 4 (group B) horses, respectively, via nasogastric intubation; 8 horses received water alone. One horse in group A that did not develop laminitis was subsequently treated again and included in group B. Before and at intervals after treatment, resting plasma glucose and serum insulin concentrations were measured and frequently sampled IV glucose tolerance tests were performed. Area under the glucose curve (AUCg) and area under the insulin curve (AUCi) were calculated, and minimal model analyses were performed.
Results—3 of 8 horses in group A and all 4 horses in group B developed laminitis. Significant treatment-time effects were detected for resting plasma glucose concentrations and AUCg. Among horses in group A, mean AUCg values at 24 and 48 hours were 34% and 32% higher, respectively, than the mean value at 24 hours. Treatment groups did not differ significantly with respect to resting serum insulin concentration, AUCi, or minimal model analysis results.
Conclusions and Clinical Relevance—In horses, laminitis can be induced and glucose dynamics altered via nasogastric administration of 5.0 g of OF/kg. An alteration in insulin dynamics was not detected following treatment with OF.
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.
