Effect of a single dose of dexamethasone on glucose homeostasis in healthy horses by using the combined intravenous glucose and insulin test

Sustained dexamethasone administration to horses results in insulin resistance, which may predispose them to laminitis. A single dose of dexamethasone is commonly used as a diagnostic aid, yet the effect of a single dose of dexamethasone on glucose homeostasis in horses is not well defined. The objective of this study was to characterize the change in glucose dynamics over time in response to a single dose of dexamethasone. A combined glucose-insulin tolerance test (CGIT) was performed on 6 adult geldings before and at 2, 24, and 72 h postdexamethasone (40 microg/kg of BW, i.v.); a minimum of 1 wk of rest was allowed between treatments. Before any treatment, the CGIT resulted in a hyperglycemic phase followed by a hypoglycemic phase. Dexamethasone affected glucose dynamics in 3 ways: 1) at 2 h, dexamethasone shortened the ascending branch of the negative phase (P < 0.001) of the test, indicating moderate insulin resistance; 2) at 24 h, dexamethasone impaired glucose clearance by extending the positive phase and eliminating the negative phase while insulin was elevated before the CGIT, indicating a decreased response to insulin; and 3) at 72 h, dexamethasone caused a deeper nadir value (P < 0.001) compared with predexamethasone, indicating an increased response to insulin. It was concluded that dexamethasone decreased the response to insulin as early as 2 h and maximally at 24 h. At 72 h, dexamethasone caused an increased response to insulin, which was unexpected.     

Effects of glycopyrrolate on cardiorespiratory function in horses anesthetized with halothane and xylazine

OBJECTIVE: To evaluate cardiopulmonary effects of glycopyrrolate in horses anesthetized with halothane and xylazine. ANIMALS: 6 horses. PROCEDURE: Horses were allocated to 2 treatment groups in a randomized complete block design. Anesthesia was maintained in mechanically ventilated horses by administration of halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, i.v.). Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of glycopyrrolate or saline (0.9% NaCl) solution. Glycopyrrolate (2.5 microg/kg, i.v.) was administered at 10-minute intervals until heart rate (HR) increased at least 30% above baseline or a maximum cumulative dose of 7.5 microg/kg had been injected. Recovery characteristics and intestinal auscultation scores were evaluated for 24 hours after the end of anesthesia. RESULTS: Cumulative dose of glycopyrrolate administered to 5 horses was 5 microg/kg, whereas 1 horse received 7.5 microg/kg. The positive chronotropic effects of glycopyrrolate were accompanied by an increase in cardiac output, arterial blood pressure, and tissue oxygen delivery. Whereas HR increased by 53% above baseline values at 20 minutes after the last glycopyrrolate injection, cardiac output and mean arterial pressure increased by 38% and 31%, respectively. Glycopyrrolate administration was associated with impaction of the large colon in 1 horse and low intestinal auscultation scores lasting 24 hours in 3 horses. CONCLUSIONS AND CLINICAL RELEVANCE: The positive chronotropic effects of glycopyrrolate resulted in improvement of hemodynamic function in horses anesthetized with halothane and xylazine. However, prolonged intestinal stasis and colic may limit its use during anesthesia.     

Clinical assessment of blood glucose homeostasis in horses: comparison of a continuous glucose monitoring system with a combined intravenous glucose and insulin test protocol

Background: The combined glucose‐insulin test (CGIT) is helpful for evaluating insulin sensitivity. A continuous glucose monitoring system (CGMS) reports changes in interstitial glucose concentrations as they occur in the blood. Use of the CGMS minimizes animal contact and may be useful when performing a CGIT. Hypothesis: Results obtained using a CGMS are useful for the evaluation of glucose responses during the evaluation of insulin sensitivity in equids. Animals: Seven mature, obese ponies. Methods: Ponies were equipped with CGMS for determination of interstitial glucose concentrations. Glucose (150 mg/kg, IV) and insulin (0.1 U/kg, IV) were administered and blood glucose concentrations determined at (minutes after time zero) 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 with a hand‐held glucometer. Blood chemistry results were compared with simultaneously obtained results using CGMS. Results: Concordance coefficients determined for comparison of blood glucose concentrations determined by a hand‐held glucometer and those determined by CGMS after the zero time point were 0.623, 0.764, 0.834, 0.854, and 0.818 (for delays of 0, 5, 10, 15, and 20 minutes, respectively). Conclusions and Clinical Importance: Interstitial glucose concentrations obtained by the CGMS compared favorably to blood glucose concentrations. CGMS may be useful for assessment of glucose dynamics in the CGIT.     

Determination of reference values for glucose tolerance, insulin tolerance, and insulin sensitivity tests in clinically normal cats

OBJECTIVE: To determine reference values and test variability for glucose tolerance tests (GTT), insulin tolerance tests (ITT), and insulin sensitivity tests (IST) in cats. ANIMALS: 32 clinically normal cats. PROCEDURE: GTT, ITT, and IST were performed on consecutive days. Tolerance intervals (ie, reference values) were calculated as means +/- 2.397 SD for plasma glucose and insulin concentrations, half-life of glucose (T1/2 glucose), rate constants for glucose disappearance (Kglucose and Kitt), and insulin sensitivity index (Si). Tests were repeated after 6 weeks in 8 cats to determine test variability. RESULTS: Reference values for T1/2glucose, Kglucose, and fasting plasma glucose and insulin concentrations during GTT were 45 to 74 minutes, 0.93 to 1.54 %/min, 37 to 104 mg/dl, and 2.8 to 20.6 microU/ml, respectively. Mean values did not differ between the 2 tests. Coefficients of variation for T1/2glucose, Kglucose, and fasting plasma glucose and insulin concentrations were 20, 20, 11, and 23%, respectively. Reference values for Kitt were 1.14 to 7.3%/min, and for SI were 0.57 to 10.99 x 10(4) min/microU/ml. Mean values did not differ between the 2 tests performed 6 weeks apart. Coefficients of variation for Kitt and SI were 60 and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: GTT, ITT, and IST can be performed in cats, using standard protocols. Knowledge of reference values and test variability will enable researchers to better interpret test results for assessment of glucose tolerance, pancreatic beta-cell function, and insulin sensitivity in cats.     

Cardiopulmonary and sedative effects of intravenous administration of low doses of medetomidine and xylazine to adult horses

OBJECTIVE: To determine the cardiopulmonary and sedative effects of medetomidine hydrochloride in adult horses and to compare those effects with effects of an equipotent dose of xylazine hydrochloride. ANIMALS: 10 healthy adult female horses. PROCEDURE: 5 horses were given medetomidine (4 microg/kg of body weight, i.v.), and the other 5 were given xylazine (0.4 mg/kg, i.v.). Heart rate, respiratory rate, arterial blood pressures, pulmonary arterial blood pressures, and cardiac output were recorded, and sedation and ataxia scores were assigned before and every 5 minutes after drug administration for 60 minutes. Rectal temperature and blood gas partial pressures were measured every 15 minutes after drug administration. RESULTS: Arterial blood pressure was significantly decreased throughout the study among horses given medetomidine and was significantly decreased for 40 minutes among horses given xylazine. Compared with baseline values, cardiac output was significantly decreased 10, 20, and 40 minutes after administration of medetomidine and significantly increased 40 and 60 minutes after administration of xylazine. Despite the significant decrease in respiratory rate in both groups, results of blood gas analyses were not significantly changed over time. Ataxia and sedation scores were of similar magnitude for the 2 groups, but ataxia persisted slightly longer among horses given medetomidine. Horses resumed eating hay 10 to 55 minutes after drug administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that equipotent low doses of medetomidine and xylazine induce comparable levels of ataxia and sedation and similar cardiopulmonary changes in adult horses.     

Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance

OBJECTIVE: To compare obese horses with insulin resistance (IR) with nonobese horses and determine whether blood resting glucose, insulin, leptin, and lipid concentrations differed between groups and were correlated with combined glucose-insulin test (CGIT) results. ANIMALS: 7 obese adult horses with IR (OB-IR group) and 5 nonobese mares. PROCEDURES: Physical measurements were taken, and blood samples were collected after horses had acclimated to the hospital for 3 days. Response to insulin was assessed by use of the CGIT, and maintenance of plasma glucose concentrations greater than the preinjection value for > or = 45 minutes was used to define IR. Area under the curve values for glucose (AUC(g)) and insulin (AUC(i)) concentrations were calculated. RESULTS: Morgan, Paso Fino, Quarter Horse, and Tennessee Walking Horse breeds were represented in the OB-IR group. Mean neck circumference and BCS differed significantly between groups and were positively correlated with AUC values. Resting insulin and leptin concentrations were 6 and 14 times as high, respectively, in the OB-IR group, compared with the nonobese group, and were significantly correlated with AUC(g) and AUC(i). Plasma nonesterified fatty acid, very low-density lipoprotein, and high-density lipoprotein-cholesterol (HDL-C) concentrations were significantly higher (86%, 104%, and 29%, respectively) in OB-IR horses, and HDL-C concentrations were positively correlated with AUC values. CONCLUSIONS AND CLINICAL RELEVANCE: Measurements of neck circumference and resting insulin and leptin concentrations can be used to screen obese horses for IR. Dyslipidemia is associated with IR in obese horses.     

Evaluation of glucose tolerance and insulin sensitivity in Ilama crias

OBJECTIVE: To investigate glucose tolerance and insulin sensitivity in llama crias. ANIMALS: 7 llamas (age range, 14 to 30 days). PROCEDURE: On each of 2 sequential days, crias were administered glucose (0.5 g/kg) via rapid i.v. injection. On 1 day (randomly determined for each cria), regular insulin (0.2 U/kg) or 0.9% NaCl solution (0.002 mL/kg) was administered i.v. 15 minutes after glucose administration. Blood samples were collected before (baseline) and at 5, 15, 30, 45, 60, 90, 120, 180, and 240 minutes after glucose administration for determination of plasma glucose and insulin concentrations; fractional turnover rates and plasma half-life of glucose were calculated. The data were compared over time and between days (ie, between glucose treatments with and without insulin administration). RESULTS: A peak plasma glucose concentration of 342 +/- 47 mg/dL was detected at 5 minutes after glucose administration and llamas cleared glucose from plasma within 60 minutes; at 15 minutes, plasma insulin concentration attained a peak value of 33 +/- 13 microU/mL (ie, triple the baseline value). During the 15- to 45-minute interval, fractional turnover rate of glucose was 1.10 +/- 0.24%/min and plasma half-life was 65.7 +/- 13.4 minutes. Insulin significantly increased glucose turnover and resulted in hypoglycemia within 75 minutes of administration. CONCLUSIONS AND CLINICAL RELEVANCE: Healthy immature llamas have glucose tolerance and insulin sensitivity superior to that of adults. However, whether sick crias retain the pancreatic sufficiency and tissue responsiveness that are likely responsible for the rapid glucose clearance in healthy individuals is not known.     

Effects of a muscarinic type-2 antagonist on cardiorespiratory function and intestinal transit in horses anesthetized with halothane and xylazine

OBJECTIVE: To evaluate the cardiorespiratory and intestinal effects of the muscarinic type-2 (M2) antagonist, methoctramine, in anesthetized horses. ANIMALS: 6 horses. PROCEDURE: Horses were allocated to 2 treatments in a randomized complete block design. Anesthesia was maintained with halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, i.v.) and mechanical ventilation. Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of methoctramine or saline (0.9% NaCl) solution (control treatment). Methoctramine was given at 10-minute intervals (10 microg/kg, i.v.) until heart rate (HR) increased at least 30% above baseline values or until a maximum cumulative dose of 30 microg/kg had been administered. Recovery characteristics, intestinal auscultation scores, and intestinal transit determined by use of chromium oxide were assessed during the postanesthetic period. RESULTS: Methoctramine was given at a total cumulative dose of 30 microg/kg to 4 horses, whereas 2 horses received 10 microg/kg. Administration of methoctramine resulted in increases in HR, cardiac output, arterial blood pressure, and tissue oxygen delivery. Intestinal auscultation scores and intestinal transit time (interval to first and last detection of chromium oxide in the feces) did not differ between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Methoctramine improved hemodynamic function in horses anesthetized by use of halothane and xylazine without causing a clinically detectable delay in the return to normal intestinal motility during the postanesthetic period. Because of their selective positive chronotropic effects, M2 antagonists may represent a safe alternative for treatment of horses with intraoperative bradycardia.     

Optimisation of the frequently sampled intravenous glucose tolerance test to reduce urinary glucose spilling in horses

Reasons for performing study: The frequently sampled i.v. glucose tolerance test (FSIGTT) is used to evaluate glucose and insulin dynamics in horses, but it has not been determined whether urinary glucose spilling (UGS) affects results. Hypothesis: UGS occurs in horses during the FSIGTT and this problem can be minimised by adjusting the dextrose and insulin dosages used. Methods: Six mature mares were included in this study. In the first phase, 6 FSIGTT procedures were performed in each horse to evaluate 6 different dextrose dosages. Six different insulin dosages were evaluated during the second phase of the study after administration of 300 mg/kg bwt dextrose. Area under the glucose (AUCg) and insulin (AUCi) curves were calculated and minimal model analyses performed. UGS was measured in the third and fourth phases of the study during the combined glucose insulin test and established FSIGTT. A new FSIGTT was developed and evaluated. Results: Positive linear effects of dextrose dosage on AUCg, AUCi and acute insulin response to glucose were detected, with AUCg reaching a plateau at doses 200 mg/kg bwt. Insulin dosage had an inverse linear effect on AUCg, but other values remained unaffected. UGS occurred during all 3 tests and was the highest for the established FSIGTT and the lowest for the new FSIGTT. The type of FSIGTT performed did not affect minimal model results. Conclusions: Results indicate that the dextrose dosage of 300 mg/kg bwt used in the established FSIGTT is too high. UGS can be reduced by lowering the dextrose dosage to 100 mg/kg bwt. Potential relevance: A new FSIGTT involving the administration of 100 mg/kg bwt dextrose followed by 20 mu/kg bwt insulin 20 min later is recommended for use in horses because this test provides adequate data for minimal model analysis while minimising UGS.     

Comparison of Insulin and Glucose Metabolism in Horses with Pituitary Pars Intermedia Dysfunction Treated Versus Not Treated with Pergolide

Equine pituitary pars intermedia dysfunction (PPID) is known to alter glucose/insulin metabolism. This study evaluated changes in parameters relating to glucose/insulin metabolism and determined whether there is a difference between pergolide-treated and untreated animals. We hypothesized that glucose/insulin dynamics in PPID horses receiving pergolide would be different than those in untreated horses. A total of 38 horses with diagnoses of PPID were included in the study (average age: 24 years). A total of 25 horses were untreated; 13 horses were treated with pergolide (>3 months). Parameters relating to glucose/insulin metabolism were determined in all horses, as follows: adrenocorticotropin-releasing hormone (ACTH), insulin, fructosamine, triglyceride, glucose, modified insulin-to-glucose ratio (MIRG), and reciprocal of the square root of insulin (RISQI). A combined glucose-insulin test (CGIT) was performed in 23 horses as not all owners agreed to the testing. Treated animals showed a tendency to have lower ACTH, but results were not significant. All animals had fructosamine levels exceeding reference values (mean value 314 ± 32 μmol/L; reference range: <280 μmol/L). There were no statistically significant differences between insulin, glucose, ACTH, triglycerides concentrations, RISQI/MIRG calculations, and CGIT results of pergolide-treated PPID and those of untreated horses. Five horses (13.2%) had combined hyperglycemia/hyperinsulinemia, whereas 7 horses (18.4%) displayed hyperglycemia, and 3 horses (7.9%) showed hyperinsulinemia alone. Forty percent of the horses with altered glucose/insulin metabolism were treated with pergolide. Based on RISQI and MIRG calculations, 19 animals displayed changes in glucose/insulin metabolism. Fourteen of twenty-three horses (61%) showed signs of insulin resistance in CGIT results. In conclusion, PPID horses frequently show alterations in glucose/insulin metabolism, but no significant differences were found between treated and untreated animals. Changes in insulin/glucose dynamics may not be a useful indicator of response to pergolide treatment.     

Influence of morphine sulfate on the halothane sparing effect of xylazine hydrochloride in horses

OBJECTIVE: To quantitate the dose and time-related effects of morphine sulfate on the anesthetic sparing effect of xylazine hydrochloride in halothane-anesthetized horses and determine the associated plasma xylazine and morphine concentration-time profiles. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of halothane in O2 and characterize the anesthetic sparing effect (ie, decrease in MAC of halothane) by xylazine (0.5 mg/kg, i.v.) administration followed immediately by i.v. administration of saline (0.9% NaCI) solution, low-dose morphine (0.1 mg/kg), or high-dose morphine (0.2 mg/kg). Selected parameters of cardiopulmonary function were also determined over time to verify consistency of conditions. RESULTS: Mean (+/- SEM) MAC of halothane was 1.05 +/- 0.02% and was decreased by 20.1 +/- 6.6% at 49 +/- 2 minutes following xylazine administration. The amount of MAC reduction in response to xylazine was time dependent. Addition of morphine to xylazine administration did not contribute further to the xylazine-induced decrease in MAC (reductions of 21.9 +/- 1.2 and 20.7 +/- 1.5% at 43 +/- 4 and 40 +/- 4 minutes following xylazine-morphine treatments for low- and high-dose morphine, respectively). Overall, cardiovascular and respiratory values varied little among treatments. Kinetic parameters describing plasma concentration-time curves for xylazine were not altered by the concurrent administration of morphine. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine decreases the anesthetic requirement for halothane in horses. Concurrent morphine administration to anesthetized horses does not alter the anesthetic sparing effect of xylazine or its plasma concentration-time profile.     

Evaluation of xylazine and ketamine for total intravenous anesthesia in horses

OBJECTIVE: To evaluate the use of xylazine and ketamine for total i.v. anesthesia in horses. ANIMALS: 8 horses. PROCEDURE: Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, i.v.), guaifenesin (75 mg/kg, i.v.), and ketamine (2 mg/kg, i.v.). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (microg/kg/min) and X and K represent xylazine and ketamine, respectively: X35 + K90 with 100% inspired oxygen (O2), X35 + K120-(O2), X35 + K150-(O2), X70 + K90-(O2), K150-(O2), and X35 + K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated. RESULTS: Heart rate and cardiac index were higher and total peripheral resistance lower in K150-(O2) and X35 + K120-air groups. The mean arterial pressure was highest in the X35 + K120-air group and lowest in the K150-(O2) group (125 +/- 6 vs 85 +/- 8 at 20 minutes, respectively). Mean Pa(O2) was lowest in the X35 + K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-(O2) (23 +/- 6 minutes and 33 +/- 8 minutes, respectively) and longest for those receiving X70 + K90-(O2) (58 +/- 28 minutes and 69 +/- 27 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses.     

The effect of xylazine and xylazine followed by insulin on blood glucose and insulin in the dairy cow

The effect of xylazine and xylazine followed 20 minutes later by insulin upon glucose metabolism and plasma insulin concentrations was examined in three cows. After doses of 0.18 mg per kg xylazine given intramuscularly (IM) or 0.15 mg per kg given intravenously (IV) hepatic glucose production increased, plasma insulin concentrations decreased to 25 to 33 per cent of control values, and there was a prolonged hyperglycaemia. When 200 units of soluble insulin were given 20 minutes after similar doses of xylazine there was a rapid fall in blood glucose and a reduction in the rate of glucose production by the liver. Xylazine-induced hyperglycaemia arose from a combination of increased hepatic glucose production and reduced plasma insulin concentrations. Peripheral tissues were still responsive to insulin and when adequate insulin was available blood glucose concentrations rapidly decreased.     

Determination of serum insulin concentration during intravenous glucose tolerance testing of healthy bulls

OBJECTIVE: To determine the insulin response curve during IV glucose tolerance testing of mature Holstein bulls. ANIMALS: 8 Holstein bulls between 5 and 8 years old and weighing between 911.5 and 1035.5 kg. PROCEDURE: A 50% glucose solution was rapidly administered IV so that each bull received a mean dose of 258 mg of glucose/kg of body weight. Serum glucose and insulin concentrations were determined before and 30, 60, 120, and 240 minutes after glucose infusion. RESULTS: Serum glucose concentrations 30 and 60 minutes after infusion were significantly greater than baseline concentration. Concentrations returned to baseline values 120 minutes after infusion. Serum insulin concentration was significantly greater 30 minutes after glucose administration, compared with baseline and 240-minute concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous glucose tolerance testing of mature Holstein bulls resulted in a characteristic insulin response curve. Baseline and peak insulin concentrations were higher in these bulls, compared with values reported for mature Norwegian Red cows.     

Cardiorespiratory and metabolic effects of xylazine, detomidine, and a combination of xylazine and acepromazine administered after exercise in horses

OBJECTIVE: To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered i.v. at twice the standard doses in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated i.v. with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race. RESULTS: All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise.     

Effects of an intravenous endotoxin challenge on glucose and insulin dynamics in horses

OBJECTIVE: To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses. ANIMALS: 16 healthy adult mares. PROCEDURES: Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via minimal model analysis. RESULTS: 13 of 16 horses had a clinical response to LPS, which was characterized by mild colic and leukopenia. Before treatment, mean +/- SD insulin sensitivity was 2.9 +/- 1.9 x 10(4) L x min(1) x mU(1); this significantly decreased to 0.9 +/- 0.9 x 10(4) L x min(1) x mU(1) 24 hours after treatment (69% reduction) and was 1.5 +/- 0.9 x 10(4) L x min(1) x mU(1) 48 hours after treatment. At baseline, mean +/- SD acute insulin response to glucose was 520 +/- 196 mU x min x L(1); this significantly increased to 938 +/- 620 mU x min x L(1) (80% increase) and 755 +/- 400 mU x min x L(1) (45% increase) at 24 and 48 hours after LPS treatment, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with baseline values, insulin sensitivity was decreased for 24 hours after IV injection of LPS, and affected horses had a compensatory pancreatic response. These disturbances in glucose and insulin dynamics may contribute to development of laminitis in horses.     

Measurement of C‐peptide concentrations and responses to somatostatin,glucose infusion,and insulin resistance in horses

Reasons for performing study: Hyperinsulinaemia is detected in horses with insulin resistance (IR) and has previously been attributed to increased pancreatic insulin secretion. Connecting peptide (C‐peptide) can be measured to assess pancreatic function because it is secreted in equimolar amounts with insulin and does not undergo hepatic clearance. Hypothesis: A human double antibody radioimmunoassay (RIA) detects C‐peptide in equine serum and concentrations would reflect responses to different stimuli and conditions. Methods: A validation procedure was performed to assess the RIA. Six mature mares were selected and somatostatin administered i.v. as a primed continuous rate infusion, followed by 50 nmol human C‐peptide i.v. Insulin and C‐peptide concentrations were measured in horses (n = 6) undergoing an insulin‐modified frequently sampled i.v. glucose tolerance test, and in horses with insulin resistance (n = 10) or normal insulin sensitivity (n = 20). Results: A human RIA was validated for use with equine sera. Endogenous C‐peptide secretion was suppressed by somatostatin and median (range) clearance rate was 0.83 (0.15–1.61) ml/min/kg bwt. Mean ± s.d. C‐peptide‐to‐insulin ratio significantly (P = 0.004) decreased during the glucose tolerance test from 3.60 ± 1.95 prior to infusion to 1.03 ± 0.18 during the first 20 min following dextrose administration. Median C‐peptide and insulin concentrations were 1.5‐ and 9.5‐fold higher, respectively in horses with IR, compared with healthy horses. Conclusions: Endogenous C‐peptide secretion decreases in response to somatostatin and increases after dextrose infusion. Results suggest that relative insulin clearance decreases as pancreatic secretion increases in response to dextrose infusion. Hyperinsulinaemia in insulin resistant horses may be associated with both increased insulin secretion and decreased insulin clearance. Potential relevance: Both C‐peptide and insulin concentrations should be measured to assess pancreatic secretion and insulin clearance in horses.     

Anesthesia by injection of xylazine, ketamine and the benzodiazepine derivative climazolam and the use of the benzodiazepine antagonist Ro 15-3505

25 horses which entered the clinic for minor surgery, received ketamine (2.2 mg/kg i.v.) for induction of anesthesia after previous sedation with xylazine (1.1 mg/kg i.v.). As soon as the horses were in the lateral recumbency, the benzodiazepine derivate climazolam was administered at a dose of 0.1 mg/kg i.v. (10 horses) or 0.2 mg/kg i.v. (15 horses). The anesthesia was maintained with repeated injections of ketamine (1.1 mg/kg i.v. every 9-12 minutes). At the end of the surgery, 20 minutes after the last ketamine injection, Ro 15-3505, a benzodiazepine antagonist, was injected at a dose of 0.01 mg/kg i.v. or 0.02 mg/kg i.v. Climazolam successfully suppressed the adverse reactions of ketamine, such as poor muscle relaxation, hyperacusis and convulsions. The benzodiazepine antagonist Ro 15-3505 allowed good control of the duration of anesthesia and--in most cases--a smooth, predictable recovery period was the result.     

Effect of general anesthesia and minor surgical trauma on urine and serum measurements in horses

OBJECTIVE: To characterize the effect of general anesthesia and minor surgery on renal function in horses. ANIMALS: 9 mares with a mean (+/- SE) age and body weight of 9+/-2 years and 492+/-17 kg, respectively. PROCEDURE: The day before anesthesia, urine was collected (catheterization) for 3 hours to quantitate baseline values, and serum biochemical analysis was performed. The following day, xylazine (1.1 mg/kg, IV) was administered, and general anesthesia was induced 5 minutes later with diazepam (0.04 mg/kg, IV) and ketamine (2.2 mg/kg, IV). During 2 hours of anesthesia with isoflurane, Paco2 was maintained between 48 and 52 mm Hg, and mean arterial blood pressure was between 70 and 80 mm Hg. Blood and urine were collected at 30, 60, and 120 minutes during and at 1 hour after anesthesia. RESULTS: Baseline urine flow was 0.92+/-0.17 ml/kg/h and significantly increased at 30 and 60 minutes after xylazine administration (2.14+/-0.59 and 2.86+/-0.97 ml/kg/h respectively) but returned to baseline values by the end of anesthesia. Serum glucose concentration increased from 12+/-4 to 167+/-8 mg/dl at 30 minutes. Glucosuria was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Transient hyperglycemia and an increase in rine production accompanies a commonly used anesthetic technique for horses. The increase in urine flow is not trivial and should be considered in anesthetic management decisions. With the exception of serum glucose concentration and urine production, the effect of general anesthesia on indices of renal function in clinically normal horses is likely of little consequence in most horses admitted for elective surgical procedures.     

Effects of alpha2-adrenergic receptor agonists on urine production in horses deprived of food and water

OBJECTIVE: To quantitate the dose- and time-related effects of IV administration of xylazine and detomidine on urine characteristics in horses deprived of feed and water. ANIMALS: 6 horses. PROCEDURE: Feed and water were withheld for 24 hours followed by i.v. administration of saline (0.9% NaCI) solution, xylazine (0.5 or 1.0 mg/kg), or detomidine (0.03 mg/kg). Horses were treated 4 times, each time with a different protocol. Following treatment, urine and blood samples were obtained at 15, 30, 60, 120, and 180 minutes. Blood samples were analyzed for PCV and serum concentrations of total plasma solids, sodium, and potassium. Urine samples were analyzed for pH and concentrations of glucose, proteins, sodium, and potassium. RESULTS: Baseline (before treatment) urine flow was 0.30 +/- 0.03 mL/kg/h and did not significantly change after treatment with saline solution and low-dose xylazine but transiently increased by 1 hour after treatment with high-dose xylazine or detomidine. Total urine output at 2 hours following treatment was 312 +/- 101 mL versus 4,845 +/- 272 mL for saline solution and detomidine, respectively. Absolute values of urine concentrations of sodium and potassium also variably increased following xylazine and detomidine administration. CONCLUSIONS AND CLINICAL RELEVANCE: Xylazine and detomidine administration in horses deprived of feed and water causes transient increases in urine volume and loss of sodium and potassium. Increase in urine flow is directly related to dose and type of alpha2-adrenergic receptor agonist. Dehydration in horses may be exacerbated by concurrent administration of alpha2-adrenergic receptor agonists.