OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally administered intermediate-acting glucocorticoids (prednisone) could predispose dogs to progression of heart disease or congestive heart failure. ANIMALS 11 client-owned dogs with allergic dermatitis and 11 matched healthy control dogs. PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO) once daily for 14 consecutive days beginning on day 0 (baseline), followed by a tapering and washout period; control dogs received no treatment. Measurements were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare changes in variables across measurement points and between dog groups. RESULTS Prednisone administration caused no significant changes in serum sodium or potassium concentration, blood glucose concentration, or target echocardiographic variables. The change from baseline in systolic arterial blood pressure at day 7 was significantly greater in prednisone-treated dogs than in control dogs. Expected changes in hematologic and serum biochemical values with prednisone administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline phosphatase and alanine aminotransferase activities) also occurred in the prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that anti-inflammatory doses of orally administered glucocorticoids have the potential to adversely impact cardiac function in dogs by causing an increase in blood pressure and thus increased cardiac afterload.

OBJECTIVE To investigate systemic changes following low-dosage prednisolone administration in dogs. ANIMALS 4 healthy purpose-bred adult male Beagles. PROCEDURES Dogs were administered prednisolone PO at a dosage of 2 mg/kg/d for 2 weeks, 1 mg/kg/d for 4 weeks, and 0.5 mg/kg/d for 3 weeks. Body weight, blood pressure, hepatic size and echogenicity, percentage of vacuolated hepatocytes, serum hepatic enzyme activities and glucose concentration, adrenal gland size, and pancreatic echogenicity were evaluated weekly for 9 weeks. RESULTS The only significant change identified was an increase in hepatic echogenicity, assessed by measuring liver-kidney contrast on ultrasonographic images. Increases in hepatic size and percentage of vacuolated hepatocytes were identified, but values did not differ from baseline values. Similarly, serum hepatic enzyme activities increased, but changes were mild and not significantly different from baseline values. Body weight, pancreatic echogenicity, and serum glucose concentration did not show noticeable changes. Mild systemic hypertension was seen, but blood pressure was not significantly different from the baseline value. Similarly, adrenal gland size steadily decreased during the first 6 weeks and increased again after the prednisolone dosage was decreased to 0.5 mg/kg/d. However, mean adrenal gland size was not significantly different from the baseline value at any time. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in dogs, administration of prednisolone at a low dosage was associated with minimal systemic effects.

Objective-To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Animals-6 healthy adult mares 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 insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations. Results-Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area under the plasma glucose curve following LPS administration was greater for the EMS-affected horses than it was for the healthy horses. Horses with EMS that received LPS or saline solution infusions had decreased insulin sensitivity over time. Conclusions and Clinical Relevance-Glucose and insulin responses to endotoxemia differed between healthy horses and horses with EMS, with greater loss of glycemic control in EMS-affected horses. Horses with EMS also had greater derangements in glucose and insulin homeostasis that were potentially stress induced. It may therefore be helpful to avoid exposure of these horses to stressful situations.

Objective—To evaluate the effect of ovariectomy on insulin sensitivity in horses and determine whether the effects of suppression of the hypothalamo-pituitary-adrenal axis differ before and after ovariectomy. Animals—6 healthy mares. Procedures—The horses underwent an IV glucose tolerance test (IVGTT), an insulin sensitivity test, and a dexamethasone suppression test before and 5 weeks after ovariectomy. Body weight, serum cortisol and plasma ACTH concentrations, serum insulin-to-blood glucose concentration ratios, and changes in blood glucose concentration with time after injection of glucose or insulin were compared before and after ovariectomy. Results—The dexamethasone injection resulted in a decrease in serum cortisol concentration before and after ovariectomy. In all horses, baseline plasma ACTH concentrations were within the reference range before and after ovariectomy. For each mare, results of an IVGTT before and after ovariectomy were considered normal. No significant differences in basal blood glucose concentration or time to reach baseline glucose concentration after an IVGTT were observed. Basal serum insulin concentration and serum insulin-to-blood glucose concentration ratios were not significantly different before or after ovariectomy, nor was the mean time to attain a 50% decrease in blood glucose concentration after insulin injection. Conclusions and Clinical Relevance—Results indicated that ovariectomy does not appear to modify dexamethasone response in horses and that it does not modify short-term measures of insulin sensitivity. Findings suggested that horses undergoing ovariectomy are not at higher risk of developing equine metabolic syndrome or hypothalamo-pituitary-adrenal axis dysfunction and associated morbidity.

Objective-To compare β-hydroxybutyrate (BHB) and glucose concentrations measured with a dual-purpose point-of-care (POC) meter designed for use in humans and a laboratory biochemical analyzer (LBA) to determine whether the POC meter would be reliable for on-farm measurement of blood glucose and BHB concentrations in sheep in various environmental conditions and nutritional states. Animals-36 pregnant mixed-breed ewes involved in a maternal feed restriction study. Procedures-Blood samples were collected from each sheep at multiple points throughout gestation and lactation to allow for tracking of gradually increasing metabolic hardship. Whole blood glucose and BHB concentrations were measured with the POC meter and compared with serum results obtained with an LBA. Results-464 samples were collected. Whole blood BHB concentrations measured with the POC meter compared well with LBA results, and error grid analysis showed the POC values were acceptable. Whole blood glucose concentrations measured with the POC meter had more variation, compared with LBA values, over the glucose ranges evaluated. Results of error grid analysis of POC-measured glucose concentrations were not acceptable, indicating errors likely to result in needless treatment with glucose or other supplemental energy sources in normoglycemic sheep. Conclusions and Clinical Relevance-The POC meter was user-friendly and performed well across a wide range of conditions. The meter was adequate for detection of pregnancy toxemia in sheep via whole blood BHB concentration. Results should be interpreted with caution when the POC meter is used to measure blood glucose concentrations.

Objective: To establish a safe anesthetic protocol with little effect on blood biochemical values and IV glucose tolerance test (IVGTT) results in Japanese black bears (Ursus thibetanus japonicus). Animals: 16 captive female Japanese black bears (5 to 17 years of age). Procedures: Bears were randomly assigned to 4 treatment groups (4 bears/group) in which various treatment combinations were administered via blow dart: tiletamine HCl and zolazepam HCl (9 mg/kg) alone (TZ), TZ (6 mg/kg) and acepromazine maleate (0.1 mg/kg), TZ (6 mg/kg) and butorphanol tartrate (0.3 mg/kg), or TZ (3 mg/kg) and medetomidine HCl (40 μg/kg). Glucose injection for the IVGTT was started 130 minutes after TZ administration. Blood samples were obtained before, at, and intermittently after glucose injection for measurement of biochemical variables as well as plasma glucose and serum insulin concentrations during the IVGTT. Rectal temperature, pulse rate, and respiratory rate were assessed every 15 minutes during the experiment. Results: Induction and maintenance of anesthesia were safely achieved with little adverse effect on cardiopulmonary function when each of the 4 anesthetic regimens was used, although mild hypothermia was induced. No difference was evident between treatment groups in blood biochemical values. Blood glucose and insulin concentration profiles during the IVGTT were similar among the bears given TZ, with or without acepromazine or butorphanol, but hyperglycemia and hypoinsulinemia developed in bears given TZ with medetomidine. Conclusions and Clinical Relevance: All 4 anesthetic regimens yielded chemical restraint without affecting clinical and biochemical values in bears, but medetomidine appeared to affect IVGTT results. For this reason, medetomidine should not be used when anesthetizing bears for IVGTTs.

Objective: To determine whether repeated oral administration of glucose and leucine during the period immediately after intense exercise would increase the release of insulin and thereby enhance glycogen synthesis in horses. Animals: 12 Standardbred horses. Procedures: In a crossover study design, after glycogen-depleting exercise, horses received oral boluses of glucose (1 g/kg at 0, 2, and 4 hours) and leucine (0.1 g/kg at 0 and 4 hours) or boluses of water (10 mL/kg at 0, 2, and 4 hours; control treatment). Blood samples for determination of glucose, insulin, and leucine concentrations were collected prior to and during a 6-hour period immediately after exercise. Biopsy specimens of a gluteus muscle were obtained before and immediately after exercise and at 3, 6, and 24 hours after exercise for measurement of glycogen concentration. Results: When glucose and leucine were administered to the horses, plasma insulin concentration was significantly higher during the 6 hours immediately after exercise than it was when water was administered to the horses. Serum glucose concentration during the 4 hours immediately after exercise was significantly higher when glucose and leucine were administered than the serum glucose concentration when water was administered. Muscle glycogen concentrations did not differ between the 2 treatments during the 24 hours after exercise. Conclusions and Clinical Relevance: Synthesis of muscle glycogen after intense intermittent exercise was not enhanced by oral boluses of glucose and leucine after exercise despite pronounced increases in plasma insulin and serum glucose concentrations.

Objective: To determine whether feeding-induced activation of translation initiation factors, specifically protein kinase B, ribosomal protein S6 kinase (S6K1), ribosomal protein S6 (rpS6), and eukaryotic initiation factor 4E binding protein 1, in horses is affected by age. Animals: 6 yearlings, six 2-year-old horses, and 6 mature horses. Procedures: After an 18-hour period of feed withholding, horses consumed a high-protein meal (2 g/kg) at time 0 and 30 minutes (postprandial state) or continued to have feed withheld (postabsorptive state). Blood samples were collected for the duration of the experimental procedures and used to determine plasma concentrations of glucose, insulin, and amino acids. At 90 minutes, biopsy specimens were collected from a gluteal muscle and used to measure phosphorylation of translation initiation factors. Results: Plasma glucose, insulin, and amino acid concentrations were elevated for the postprandial state, compared with results for the postabsorptive state, regardless of age. Phosphorylation of protein kinase B, S6K1, rpS6, and eukaryotic initation factor 4E binding protein 1 was increased for the postprandial state. There was an effect of age with increased phosphorylation of S6K1 at Thr389 and rpS6 at Ser235/236 in the yearlings and mature horses, compared with results for the 2-year-old horses. Conclusions and Clinical Relevance: Food consumption resulted in an increase in the activation of translation initiation factors, with the highest degree of responsiveness in the yearlings. This indicated that increased muscle accretion seen during growth could be a result of increased rates of muscle protein synthesis in response to a meal stimulus.

Objective: To determine the effectiveness of preinduction hyperbaric oxygen treatment (HBOT) in ameliorating signs of experimentally induced endotoxemia in horses. Animals: 18 healthy adult horses. Procedures: Horses were randomly assigned to 1 of 3 equal-sized treatment groups to receive normobaric ambient air and lipopolysaccharide (LPS), HBOT and LPS, or HBOT and physiologic saline (0.9% NaCl) solution. Horses were physically examined, and blood was obtained for a CBC and to determine concentration or activity of plasma tissue necrosis factor-α, blood lactate, and blood glucose before the horses were treated with HBOT and then intermittently for 6 hours after administration of LPS or physiologic saline solution. Results: All LPS-treated horses developed signs and biochemical and hematologic changes consistent with endotoxemia. Treatment with HBOT significantly ameliorated the effect of LPS on clinical endotoxemia score but did not significantly improve other abnormalities associated with endotoxemia. Conclusions and Clinical Relevance: The protective effect of HBOT was minimal, and results did not support its use as a treatment for horses prior to development of endotoxemia.

Objective--To measure arterial and venous blood gas, coagulation, and fibrinolysis variables in blood from isolated segments of control and ischemic large colons for the purpose of identifying variables for rapid, indirect assessment of colonic mucosal injury. Design--Variables were determined at specific intervals during the 4-hour study (3 hours of ischemia and 1 hour of reperfusion). Animals--Seven clinically normal horses between 2 and 15 years old. Procedure--Horses underwent laparotomy and occlusion of the lumen and vasculature of the mid-portion of the pelvic flexure of the large colon. During ischemia of 1 randomly-chosen colonic segment, variables were measured to determine colonic mucosal damage and were compared with histologic scores of colonic biopsy specimens. Results--Significant (P < 0.05) differences from control values were observed over time for venous pH, Pco2, PO2, oxygen saturation, oxygen content, arteriovenous oxygen difference, and lactate and glucose concentrations. Mean histologic scores of biopsy specimens obtained from ischemic colons were significantly (P < 0.05) greater (indicating greater damage) than those from control colons, and increased significantly (P < 0.05) with duration of ischemia. Conclusions--Venous lactate, oxygen saturation, and PO2 values were the most significant predictors of the severity of histologic damage within the ischemic colons (R2 = 0.661). Clinical Relevance-Venous blood gas and lactate values in the large colon are good predictors of the amount of intestinal damage incurred during 3 hours of ischemia, and may be clinically useful for the rapid determination of colonic viability.