After IV administration of 0.5 mg of glucagon/cat, glucose tolerance and insulin secretory response were evaluated in 10 lean cats, 10 obese cats, and 30 cats with diabetes mellitus. Blood samples for glucose and insulin determinations were collected immediately before and at 5, 10, 15, 30, 45, and 60 minutes after IV administration of glucagon. Baseline serum insulin concentration and insulin secretory response were used to classify diabetes mellitus in the 30 cats as type I or type II. Mean (+/- SEM) baseline and 30-minute serum glucose concentrations in obese cats were significantly (P < 0.05) decreased, compared with values in lean cats, but were similar at all other blood sample collection times. Serum glucose concentration in diabetic cats was significantly (P < 0.05) greater than values in obese and lean cats at all blood sample collection times. Two statistically different insulin responses to IV administration of glucagon were seen in diabetic cats. Of the 30 diabetic cats, 23 had minimal insulin secretory response after glucagon administration (ie, serum insulin concentration was at or below sensitivity of the insulin assay). Seven diabetic cats had baseline serum insulin concentration similar to that of obese cats and significantly (P < 0.05) greater than that of lean cats and of the other 23 diabetic cats. In these 7 diabetic cats, serum insulin concentration increased after glucagon administration. Total insulin secretion was not significantly different between these 7 diabetic cats and the lean and obese cats, and was significantly (P < 0.05) greater than total insulin secretion in the other 23 diabetic cats. Results support existence of type-I and type-II diabetes mellitus in cats.

Pharmacokinetic variables of ibuprofen were studied in 6 adult lactating dairy goats after single administration of the drug (14 and 25 mg/kg of body weight, IV, and 50 and 100 mg/kg, PO). Each of the goats was given all doses, with a minimum of 1 week between doses. Ibuprofen concentration in serum was analyzed by use of high-performance liquid chromatography. The lower limit of detection for the ibuprofen assay was 50 ng/ml. Ibuprofen pharmacokinetic variables after IV administration best fit an open two-compartment model. Geometric mean (range) volume of distribution at steady state was 0.16 (0.11 to 0.19) and 0.17 (0.15 to 0.19) lag, and terminal half-life was 1.08 (0.79 to 1.70) and 1.27 (1.03 to 1.88) hours, for ibuprofen dosages of 14 and 25 mg/kg, respectively. After 50 and 100 mg/kg administered orally, bioavailability was 90.8 and 106%, respectively. Area under the curve increased linearly with dose administered. Adverse effects were not observed in goats given ibuprofen.

The pattern of vertical ground reaction force redistribution among limbs during episodes of acute synovitis of the stifle in 12 mixed-breed dogs was investigated as an adjunct to a blinded nonsteroidal anti-inflammatory drug efficacy study. Without regard to drug efficacy groupings, the redistribution of vertical forces before and during the acute synovitis episode was evaluated by analysis of gait, using a force platform. Acute synovitis was induced by intrasynovial injection of sodium urate crystals. Simultaneously, each dog was given 1 of 4 treatment regimens, including IV injection of sterile saline solution (as a negative control), phenylbutazone (as a positive control), or 1 of 2 proprietary nonsteroidal anti-inflammatory drugs. Postinjection analyses took place at 2, 4, 8, 12, 24, and 36 hours. The peak vertical force redistribution in the 3 untreated limbs of the dogs was described. The greatest redistribution sm observed 4 hours after substance injection when the synovitis was clinically at maximum. Thereafter, there was steady improvement and the dogs had a clinically normal gait 24 hours after substance injection. During synovitis, peak vertical force increased in the contralateral hind limb. During the more severe synovitis episodes, force was decreased in both forelimbs. There was good correlation between severity of lameness and peak vertical force response in the contralateral hind limb. Results of the study indicate that the untreated limbs of the same animal should not be used as a control during acute lameness studies.

Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine penicillin G/kg body weight were administered to yearling beef steers by intramuscular injection daily for five consecutive days were investigated. These dosages are in excess of product label recommendations, but are in the range of procaine penicillin G dosages that have been administered for the treatment of some feedlot bacterial diseases. The approved dose in Canada is 7,500 IU/kg body weight intramuscularly, once daily, with a withdrawal period of five days. Based on the tissue residue data from this study, the appropriate withdrawal period is ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg body weight dose when administered intramuscularly to yearling beef steers. In a related study, 18 yearling beef steers received 66,000 IU of procaine penicillin G/kg body weight administered by subcutaneous injection, an extra-label treatment in terms of both dose and route of administration, typical of current practice in some circumstances. Deposits of the drug were visible at subcutaneous injection sites up to ten days after injection, with more inflammation and hemorrhage observed than for intramuscular injections of the same dose. These results suggest that procaine penicillin G should not be administered subcutaneously at high doses; and therefore a withdrawal period was not established for subcutaneous injection.

Flunixin meglumine and phenylbutazone are nonsteroidal anti-inflammatory drugs commonly used for the management of colic, endotoxemia, and musculoskeletal disorders in equids. Although it is not usually recommended, there appears to be an increasing trend to use nonsteroidal anti-inflammatory drugs in combination to enhance or prolong their effects. Therefore, we studied the effect of concurrent administration of flunixin (1.1 mg/kg of body weight, IV) as flunixin meglumine and phenylbutazone (2.2 mg/kg, IV) on the pharmacokinetics of each drug and on in vitro thromboxane B2 production. Pharmacokinetic variables calculated for each drug when given alone and in combination were similar to those reported. Serum thromboxane B2 production was significantly (P = 0.05) suppressed for 12, 8, and 24 hours after administration of flunixin, phenylbutazone, and the drugs in combination, respectively. These results indicate that although concurrent administration of these drugs at the aforementioned dosages does not alter either drug disposition or clearance, it prolongs their pharmacologic effect.

Desoxycorticosterone pivalate was administered IM to juvenile Beagles at 0, 2.2, 6.6, or 11 mg/kg of body weight daily over a consecutive 3-day period every 28 days (equivalent to a cumulative monthly dosage of 0, 6.6, 19.8, or 33 mg/kg) for 6 months. Polyuria, polydipsia, and decreases in serum potassium and BUN concentrations were detected while the dogs were being treated. Transient increases in serum sodium concentrations also were detected. The treated males had significant decreases in body weight gain, resulting in an 18% decrease in body weight in the 11-mg/kg dosage group, compared with the controls. The weights of the adrenal glands, epididymides, and testes also were lower in the treated males. Organ weights for the 2.2, 6.6, and 11-mg/kg dosage groups were: 86, 79, and 69%, respectively, of the controls (adrenal glands); 80, 70, and 68%, respectively, of the controls (epididymides); and, 79, 75, and 67%, respectively, of the controls (testes). When normalized to body weight, these decreases in organ weight were still dosage-dependent, but the differences were less remarkable. In contrast, the relative weight (to body weight) of the kidneys (males and females) and of the thyroid and parathyroid glands (males) were higher dosage-dependently. All of the treatment-related effects, other than organ and body weight changes, appeared to be reversible following the cessation of treatment. On the basis of these results, it was concluded that treatment with desoxycorticosterone pivalate could be tolerated, even when given at dosages 15-fold the therapeutic dosage of 2.2 mg/kg every 25 days.

Ouabain, a cardiac glycoside, binds to the Na+-K+i-adenosine triphosphatase (Na+ pump) and prevents active transport of Na+ and K+ across cell membranes. We used [3H]ouabain to quantify the number and affinity of Na+ pumps in skeletal muscle from Quarter Horses with the muscular disorder hyperkalemic periodic paralysis (HYPP). [3H]Ouabain-binding properties of gluteal muscle from clinically normal and affected horses were used to determine whether altered Na+ pump number or affinity could contribute to the pathologic features of muscle in affected horses. Foals and adult horses with HYPP were compared with age-matched clinically normal horses. The number of [3H]ouabain-binding sites in adult gluteal muscle was not different between the 2 types of horses (85.7 +/- 8.9 pmol of [3H]ouabain-binding sites/g [wet muscle weight] in horses with HYPP vs 100.2 +/- 8.8 pmol/g in clinically normal adult horses). Gluteal muscles in HYPP-affected and clinically normal foals also contained a similar number of [3H]ouabain-binding sites (222.3 +/- 21.0 pmol/g vs 225.3 +/- 24.2 pmol/g, respectively). The affinity of these binding sites for ouabain was not different, between adults or foals, in clinically normal or affected horses. Our results indicate that membrane events underlying the periodic episodes of paralysis in horses with HYPP are not attributable to quantitative changes in Na+ pump number or affinity. Our data cannot exclude the possibility that the specific activity of the Na+ pump is altered in muscle from HYPP-affected horses.

Right dorsal colon fistulas, 2.5 cm in diameter, were created in 2 healthy ponies, using a 2-stage surgical procedure. The first stage consisted of resection of portions of the 16th and 17th ribs on the right side, followed by surgical creation of a 6- to 8-cm-diameter adhesion between the right dorsal colon and the body wall. Fistulas were created approximately 2 weeks after the first surgery by sharp dissection through the adhesion into the lumen of the colon. The fistulas have been satisfactorily maintained for > 2 years by de Pezzer catheters (45 F). Ponies with fistulas have been used for gastrointestinal experiments.

Characteristic alterations in the serum and urine biochemical profiles of Doberman Pinschers with congestive heart failure (CHF) resulting from idiopathic dilated cardiomyopathy were determined. We compared these alterations with those observed in 2 other models of CHF: rate overload induced by rapid ventricular pacing in dogs, and biventricular hypertrophy and dilatation induced in turkey poults by furazolidone toxicosis. Serum and urine biochemical changes in both models of CHF in dogs were mild to moderate in degree, and were moderately consistent, They could be attributed to secondary neurohumoral, hepatic, and renal effects of heart failure. The most marked and consistent changes observed were mildly decreased anion gap that developed, in part, because of decreased serum sodium concentration, moderately increased catecholamine concentrations, moderate lactaciduria, hyposthenuria, and mildly increased urea concentrations and liver enzyme activities. In birds with furazolidone cardiomyopathy, we observed mild increases in serum urate concentration, liver and muscle enzyme activities, but moderately increased sodium concentration with decreased chloride concentration. In the pacing and furazolidone models, in which CHF was rapidly induced, moderate to marked hypoproteinemia was attributable to decreases in albumin and globulin concentrations. Using the avian model we found that the hypoproteinemia could be largely attributed to blood volume expansion, and to a lesser extent, inanition. Development of hypoalbuminemia during rapid ventricular pacing and furazolidone treatment may contribute to the effects of rate overload or drug toxicity in the pathogenesis of CHF, because hypoalbuminemia may contribute to altered hemodynamics and neuroendocrine system activation. Our data indicate that clinical biochemical analysis of serum and urine may be useful for assessing progression of CHF.

Plasma cortisol and corticosterone responses of 8 clinically normal adult ferrets to synthetic ACTH (cosyntropin) were evaluated. Cosyntropin was administered iv at 4 dosages (0.5, 1.0, 5.0, and 10 micrograms/kg of body weight) at 2- to 4-week intervals, with blood samples collected 60 and 120 minutes after injection. After completion of the studies, an additional ACTH stimulation test was performed by administering cosyntropin (1.0 micrograms/kg) IM. The baseline plasma cortisol concentrations from all studies ranged from 25.9 to 235 nmol/L (mean +/- SEM = 73.8 +/- 7.0 nmol/L), and plasma corticosterone values ranged from 1.7 to 47 nmol/L (mean +/- SEM = 8.3 +/- 1.1 nmol/L). After iv administration of cosyntropin, plasma concentrations of cortisol and corticosterone increased significantly (P < 0.05) and reached peak values at 60 minutes; however, there were no significant differences between plasma cortisol or corticosterone responses to the 4 dosages of cosyntropin. Intramuscular administration of 1.0 Kg of cosyntropin/kg induced increases in plasma cortisol and corticosterone concentrations that were similar to the responses induced by iv administration of cosyntropin. The mean molar ratio of cortisol to corticosterone, calculated from the resting plasma concentrations, was approximately 9:1, whereas the ACTH-stimulated cortisol to corticosterone ratio was approximately 4:1. Results of this study indicated that administration of cosyntropin to clinically normal ferrets, at dosages ranging from 0.5 to 10 micrograms/kg, increased plasma concentrations of cortisol and corticosterone. Although cosyntropin stimulates the adrenocortical secretion of cortisol and corticosterone, cortisol appears to be the predominate circulating glucocorticoid in ferrets.