Effects of multiple intramuscular injections and doses of dexamethasone on plasma cortisol concentrations and adrenal responses to ACTH in horses

Adrenocortical function was assessed in horses given multiple IM doses of dexamethasone to determine the duration of adrenocortical suppression and insufficiency caused by 2 commonly used dosages of dexamethasone (0.044 and 0.088 mg/kg of body weight). Dexamethasone was administered at 5-day intervals for a total of 6 injections. Daily blood samples were collected. The plasma was frozen and later assayed for cortisol. An ACTH response test was determined 2 days before the first injection of dexamethasone and again 8 days after the last dexamethasone injection. Maximum suppression of plasma cortisol was observed in horses given both dosages of dexamethasone (0.044 and 0.088 mg/kg). Plasma cortisol concentrations returned to base-line values in all horses by 4 days after dexamethasone injection. Normal ACTH responses observed after 6 dexamethasone injections given at 5-day intervals indicated that measurable adrenal atrophy did not develop under the conditions of this study.     

Effects of dexamethasone infusion on the plasma cortisol response to cosyntropin (synthetic ACTH) injection in normal dogs

Graded dosages of cosyntropin (synthetic corticotropin) were injected into groups of normal dogs on consecutive days. On the first day, cosyntropin was administered alone and, on the second, dogs were infused with dexamethasone three hours before cosyntropin injection. Adrenocortical function was assessed by sequential measurement of plasma cortisol (hydrocortisone) concentration. While no response differences were noted to the various amounts of cosyntropin injected with or without dexamethasone pretreatment, the magnitude of adrenocortical response was significantly greater in dogs infused with dexamethasone. It is concluded that dexamethasone pretreatment renders the canine adrenal cortex more responsive to a subsequent injection of cosyntropin. The combined dexamethasone infusion-cosyntropin injection test produces consistent adrenocortical responses in normal dogs, and has potential value in evaluation of adrenopathic dogs.     

Effects of low dosages of intravenous dexamethasone on serum cortisol concentrations in the normal cat

The suppressive effects of three different low dosages of dexamethasone (5, 10 and 15 micrograms kg-1) on serum cortisol concentrations were evaluated in 10 normal cats. On four different days, serum was collected before and at two, four, six and eight hours after the intravenous administration of saline or dexamethasone. Following the administration of saline, no significant difference in mean serum cortisol concentrations was noted between the basal or postinjection values. In contrast, mean serum cortisol concentrations decreased significantly (P less than 0.05) by two hours and remained significantly below mean basal values eight hours after injection of all three dosages of dexamethasone. The degree of cortisol suppression became progressively greater as the dosages of dexamethasone were increased. After administration of the highest dose of dexamethasone (15 micrograms kg-1), serum cortisol decreased to below 5 ng ml-1 by two to four hours and remained suppressed (under 5 ng ml-1) eight hours after injection in all cats. In contrast, two of the 10 cats showed a slight escape from cortisol suppression by eight hours after injection of dexamethasone at the dosage of 10 micrograms kg-1, whereas a dosage of 5 micrograms kg-1 failed to suppress cortisol concentrations below 10 ng ml-1 at any of the sampling times in one cat and was associated with increasing serum cortisol concentrations at eight hours after injection in three cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of single intravenous doses of dexamethasone on baseline plasma cortisol concentrations and responses to synthetic ACTH in healthy dogs

The duration of adrenocortical suppression resulting from a single IV dose of dexamethasone or dexamethasone sodium phosphate was determined in dogs. At 0800 hours, 5 groups of dogs (n = 4/group) were treated with 0.01 or 0.1 mg of either agent/kg of body weight or saline solution (controls). Plasma cortisol concentrations were significantly (P less than 0.01) depressed in dogs given either dose of dexamethasone or dexamethasone sodium phosphate by posttreatment hour (PTH) 2 and concentrations remained suppressed for at least 16 hours. However, by PTH 24, plasma cortisol concentrations in all dogs, except those given 0.1 mg of dexamethasone/kg, returned to control values. Adrenocortical suppression was evident in dogs given 0.1 mg of dexamethasone/kg for up to 32 hours. The effect of dexamethasone pretreatment on the adrenocortical response to ACTH was studied in the same dogs 2 weeks later. Two groups of dogs (n = 10/group) were tested with 1 microgram of synthetic ACTH/kg given at 1000 hours or 1400 hours. One week later, half of the dogs in each group were given 0.01 mg of dexamethasone/kg at 0600 hours, whereas the remaining dogs were given 0.1 mg of dexamethasone/kg. The ACTH response test was then repeated so that the interval between dexamethasone treatment and ACTH injection was 4 hours (ACTH given at 1000 hours) or 8 hours (ACTH given at 1400 hours). Base-line plasma cortisol concentrations were reduced in all dogs given dexamethasone 4 or 8 hours previously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma endogenous ACTH concentrations and plasma cortisol responses to synthetic ACTH and dexamethasone sodium phosphate in healthy cats

Plasma cortisol responses of 19 healthy cats to synthetic ACTH and dexamethasone sodium phosphate (DSP) were evaluated. After administration of 0.125 mg (n = 5) or 0.25 mg (n = 6) of synthetic ACTH, IM, mean plasma cortisol concentrations increased significantly (P less than 0.05) at 15 minutes, reached a peak at 30 minutes, and decreased progressively to base-line values by 120 minutes. There was no significant difference (P greater than 0.05) between responses resulting from the 2 dosage rates. After administration of 1 mg of DSP/kg of body weight, IV (n = 7), mean plasma cortisol concentrations decreased at postadministration hour (PAH) 1, and were significantly lower than control cortisol concentrations at PAH 4, 6, 8, 10, and 12 (P less than 0.01). Administration of 0.1 mg of DSP/kg, IV (n = 8) or 0.01 mg of DSP/kg, IV (n = 14) induced results that were similar, but less consistent than those after the 1 mg of DSP/kg dosage. Mean plasma cortisol concentrations returned to base-line values by PAH 24. There was not a significant difference between the 3 doses (P greater than 0.05) at most times. Measurement of endogenous ACTH in 16 healthy cats revealed plasma ACTH of less than 20 to 61 pg/ml. Seemingly, administration of synthetic ACTH consistently induced a significant (P less than 0.05) adrenocortical response in healthy cats. On the basis of time-response studies, post-ACTH stimulation cortisol samples should be collected at 30 minutes after ACTH administration to ensure detection of peak adrenocortical response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma levels of ACTH and cortisol in normal and critically-ill neonatal foals

Veterinary Research Communications -     

Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses

OBJECTIVE: To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. ANIMALS: 6 adult Standardbreds. PROCEDURES: In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations. RESULTS: Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21. CONCLUSIONS AND CLINICAL RELEVANCE: The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.     

Systemic dexamethasone concentration in horses after continued topical treatment with an ophthalmic preparation of dexamethasone.

OBJECTIVE: To determine concentrations of dexamethasone in serum and urine of horses treated repeatedly with a topically administered ophthalmic dexamethasone preparation. ANIMALS: 4 clinically normal horses (2 mares, 2 geldings). PROCEDURE: 0.1% dexamethasone ophthalmic ointment was administered to the left eye of each horse every 5 to 9 hours for 8 consecutive days, yielding an estimated cumulative dexamethasone dose of 6.4 microg/kg of body weight. Serum and urine samples were obtained before the first dexamethasone treatment, on days 4 and 8 of treatment, and 24, 48, and 96 hours after cessation of treatment. To detect small concentrations of dexamethasone, serum and urine samples were analyzed by use of a competitive enzyme immunoassay. RESULTS: During the period of continued topical treatment, serum dexamethasone concentrations increased to between 0.10 and 0.49 ng/ml, then decreased below the limit of detection (0.06 ng/ml) within 24 hours after cessation of treatment. Dexamethasone also was detected in urine samples at concentrations of up to 0.98 ng/ml. CONCLUSIONS: Repeated topical administration of dexamethasone ophthalmic ointment generated low, but detectable glucocorticoid concentrations in serum and urine. CLINICAL RELEVANCE: Because treatment of performance horses with dexamethasone is prohibited for most types of competitions and because enhanced glucocorticoid detection methods may result in positive test results, owners and trainers may wish to reconsider entering horses in competitions during periods of treatment with ophthalmic dexamethasone preparations.     

Effects of a mock ultrasonographic procedure on cortisol concentrations during low-dose dexamethasone suppression testing in clinically normal adult dogs

OBJECTIVE: To determine whether the stress of an ultrasonographic procedure would interfere with the suppressive effect of dexamethasone during a low-dose dexamethasone suppression test (LDDST) in healthy dogs. ANIMALS: 6 clinically normal adult dogs. PROCEDURE: In phase 1, an LDDST was performed 5 times at weekly intervals in each dog. Serum samples were obtained 0, 2, 4, 6, and 8 hours after dexamethasone injection. A mock 20-minute abdominal ultrasonographic examination was performed on all dogs at each time point during the LDDST on weeks 2 through 5. In phase 2, serum cortisol concentrations were measured before and immediately after a 20-minute mock abdominal ultrasonographic examination, as described for phase 1. RESULTS: We did not detect significant differences after dexamethasone injection when comparing median cortisol concentrations for weeks 2 to 5 (mock ultrasonographic procedure) with median concentration for week 1 (no mock ultrasonographic procedure). For 5 of the 6 dogs, cortisol concentrations after dexamethasone injection decreased to < 35.9 nmol/L after each mock ultrasonographic procedure and remained low for the duration of the LDDST. In phase 2, all dogs had significant increases in cortisol concentrations immediately after the mock ultrasonographic procedure. CONCLUSIONS AND CLINICAL RELEVANCE: A 20-minute mock abdominal ultrasonographic examination performed during LDDST did not alter results of the LDDST in most dogs. Cortisol concentrations measured immediately after a mock ultrasonographic examination were significantly increased. Ultrasonographic procedures should be performed a minimum of 2 hours before collection of samples that will be used to measure cortisol concentrations.     

Effects of dietary cation-anion difference on blood cortisol and ACTH levels in reproducing ewes

Formulation of rations to induce a compensated metabolic acidosis in the post-partum cow has proved a useful strategy for prevention of milk fever. Such acidification improves the ability of the animal to maintain calcium homeostasis by promoting the absorption of calcium from the intestine and mobilization of calcium from the bone. In humans, an acidogenic diet results in mild metabolic acidosis in association with a state of cortisol excess and this increase in plasma cortisol may increase bone catabolism. The objective of our experiment was to induce acidification by anionic salt supplementation and to study the effects of anionic supplementation on plasma cortisol and adrenocorticotropic hormone (ACTH) levels in sheep. Twenty-seven twin-bearing sheep were assigned to two experimental groups and a control group, depending on dietary cation-anion difference (DCAD) (+272.6, -88.9 and +164.5 mEq/kg DM respectively). Sheep assigned to each dietary treatment received their respective rations beginning 6 weeks pre-partum and continuing until 12 days post-partum. Anionic diet induced a non-respiratory systemic acidosis in association with a mild increase in plasma cortisol concentration without changes in plasma ACTH levels. Our data suggest that the mild hypercortisolism observed in sheep fed the anionic diet may not be an effector for bone resorption induced by anionic salts. A mild hypercortisolism of this magnitude may lead to osteoporosis but this might require many years of adrenal hypersecretion while anionic salts are only used during the last weeks of pregnancy.     

地塞米松对山羊皮质醇分泌和瘤胃生物钟基因表达的影响

为了研究地塞米松对山羊皮质醇分泌和瘤胃生物钟基因表达的影响,试验选用10只装有永久性瘤胃瘘管的波尔杂交山羊,随机分为对照组(n=5)和地塞米松组(n=5),对照组注射生理盐水,地塞米松组注射地塞米松(0.2 mg/kg),每天注射1次,连续注射21 d。试验结束后,采集血液和瘤胃组织;放射免疫分析法(radioimmunoassay,RIA)检测血浆皮质醇含量;Real-time PCR检测瘤胃生物钟基因表达量。结果显示:与对照组相比,地塞米松组血浆皮质醇浓度显著降低(P0.05),瘤胃液中皮质醇浓度无显著变化(P0.05),瘤胃上皮组织中永恒蛋白基因(Tim)和肌肉芳香烃受体核转运样蛋白1(Bmal1)mRNA表达显著上调(P0.05);相关性分析结果显示:血浆皮质醇浓度与瘤胃上皮组织中Tim(R=-0.64,P=0.08)和Bmal1(R=-0.62,P=0.09)mRNA表达呈负相关趋势,瘤胃中皮质醇浓度与瘤胃上皮组织中Bmal1 mRNA表达呈显著负相关(R=-0.84,P0.05)。结果提示,外源性地塞米松降低山羊体内内源性皮质醇的生成,上调瘤胃上皮组织中生物钟基因的表达,且生物钟基因表达水平与血液、瘤胃液中皮质醇浓度呈高度负相关。     

Effects of misoprostol and omeprazole on basal gastric pH and free acid content in horses

The basal gastric pH and free acid contents from five young adult healthy horses were determined at one hour intervals for eight hours. The basal gastric pH and free acid contents varied from 1.63 +/- 0.06 to 1.97 +/- 0.11 and 26.42 +/- 4.14 to 17.92 +/- 5.28 mmol litre-1, respectively. Misoprostol, a methylester analogue of prostaglandin (5 micrograms kg-1, orally) produced a time-dependent increase in the basal gastric pH to above 3.5 (P less than 0.05) at three, four and five hours after administration with a concomitant reduction of 80 to 90 per cent in the basal gastric free acid contents throughout the eight hour period monitored. Omeprazole, a benzimidazole derivative (0.5 mg kg-1, intravenously) increased the basal gastric pH to above 3.5 at two and three hours after administration with a concomitant reduction of 65 to 90 per cent in the basal gastric free acid contents for seven of the eight hour periods monitored. These results confirm that the horse is a basal acid secretor, and both misoprostol and omeprazole are effective inhibitors of the basal gastric acid secretion, thus establishing that both prostaglandins and H+/K+-ATPase play an important role in controlling parietal cell function of the equine gastric mucosa.     

Hyaluronic acid concentration in synovial fluid from normal and arthritic joints of horses

A method previously described was used to determine the hyaluronic acid concentration in synovia from normal and arthritic horse joints. The concentration of hyaluronic acid in the synovia from arthritic joints was found to be significantly lower than the concentration in fluid from normal joints.     

Effects of dioctyl sodium sulfosuccinate on hematological values in normal horses

In several horses referred for evaluation of colic, we observed marked leukopenia (attributable to neutrophil counts <2,000/μl) which was inconsistent with the mild nature of abdominal pain, absence of fever, or lack of signs of endotoxemia. In all cases, large bowel impaction has been diagnosed via rectal palpation prior to admission and dioctyl sodium sulfosuccinate (DSS) had been one of the medications administered. To investigate the hypothesis that DSS administration may lead to bowel irritation, margination of neutrophils, and development of leukopenia (neutropenia), the effects of DSS administration (20 mg/kg via a nasogastric tube) on clinical and hematologic values were studied in eight clinically normal horses. No changes were detected in any of the clinical values assessed in these horses and neither leukopenia nor neutropenia was observed following DSS administration. A trend for plasma total protein concentration to increase four hours after DSS administration (in comparison to control data) suggested that DSS may enhance secretion of fluid into the bowel in treated horses. In conclusion, the results did not support the hypothesis that the leukopenia observed in horses with colic could be attributed to DSS administration. Whether DSS has more significant effects in horses with altered bowel motility and mucosal integrity during colic episodes is not known.