Effects of low doses of the neuroleptic drugs droperidol and zuclopenthixol, combined with a subanalgesic dose of the opioid mu-agonist, fentanyl, on mechanical nociceptive thresholds were evaluated in sheep. Intravenously administered droperidol (5 micrograms/kg of body weight) did not induce any change in the nociceptive thresholds when administered alone, but caused marked increase in threshold responses when combined with a subanalgesic dose of fentanyl (5 micrograms/ kg). Similarly, a combination of iv administered zuclopenthixol (100 micrograms/kg) and fentanyl induced significant (P < 0.05) antinociceptive effects, whereas zuclopenthixol administered iv alone had no effect on the threshold responses. Intrathecal administration of a low dose of droperidol (5-microgram total dose) combined with iv administered fentanyl also increased mechanical thresholds significantly (P < 0.05). These results indicate that interactions exist between dopaminergic and opioid systems in the processing of nociceptive information and that these effects may, at least partially, be mediated spinally.

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.

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.

In 6 cats, mean +/- SEM baseline plasma concentrations of cortisol, corticotropin, and alpha-melanocyte-stimulating hormone (alpha-MSH) were 87 +/- 16 nmol/L, 73 +/- 14 ng/L, and 129 +/- 12 ng/L, respectively. The cats were subjected to: handling and subsequent skin testing without anesthesia; anesthesia with 50 mg of ketamine HCl and 2.5 mg of diazepam given IV, immediately followed by handling and skin testing; and anesthesia and handling as previously described, but without skin testing. Significant (P < 0.05; multivariate analysis for repeated measures) increase in plasma cortisol, corticotropin, and alpha-MSH concentrations was observed until 20 minutes after the start of the experiments in cats undergoing physical restraint and subsequent skin testing with or without preceding anesthesia. These responses were largely abolished when anesthesia with ketamine and diazepam was only followed by handling. We conclude that, during stress in cats (in contrast to dogs), the pituitary intermediate lobe is activated to secrete alpha-MSH. In addition, the cortisol response after skin testing of cats under anesthesia may be a reasonable explanation for the reported weak skin test reactivity in cats.

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.

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.

Undifferentiated distal respiratory tract disease (nasal discharge, cough, pneumonia) in foals (1 to 8 months old) is a burdensome economic problem on breeding farms yet, the infective agents associated with these episodes have not been well described. Possible causes of these episodes of illness were investigated by culturing specimens of proximal and distal airways of clinically diseased foals (n = 101), prior to any treatment, for aerobic and anaerobic bacteria and viruses (rhinoviruses, equine arteritis virus, equine herpesvirus subtype 1 [EHV-1], influenza virus, and adenovirus). Pairs of sera (n = 47) were examined for antibodies to influenza A virus, equine subtypes 1 and 2, EHV-1, and adenovirus antigens, and sera obtained from foals during acute infection were examined for antibodies (by agar gel immunodiffusion [AGID]) to equi factor antigens of Rhodococcus equi. Viruses were not isolated from the proximal (swab) or distal (bronchial lavage) airway specimens in foals, and only 2 of 47 randomly selected foals seroconverted to EHV-1. Serotiters to the other viruses were low and frequently decreasing between samples, which was compatible with maternally derived antibody. Streptococcus zooepidemicus was the predominant isolate from bronchial lavage specimens (88/101 cases), accompanied by alpha-hemolytic streptococci (8 cases), Bordetella bronchiseptica (13 cases), Staphylococcus epidermidis (9 cases), and other organisms in lesser frequency. Only Str zooepidemicus was recovered significantly (P < 0.05) more often in cases than in controls. The AGID test was found useful to detect 1/26 with presumed exposure to R equi, but positive tests results did not correspond well with bacterial culture results; positive AGID results were recorded in 34% of culture-negative foals. However, foals from which R equi was isolated were distinctive from the other foals on the basis of fever (> 39 C), lack of nasal discharge, blood neutrophilia and decreased percentage of neutrophils in bronchial lavage fluid samples. Isolation of Str zooepidemicus was significantly (P < 0.01) associated with increasing neutrophil percentage in bronchial lavage fluid. In conclusion, the pathogenic roles of Str zooepidemicus and R equi were established in this group of foals with distal respiratory tract infections by use of clinical, endoscopic, hematologic, and cytologic methods. There was no evidence of a viral cause for these infections, indicating that manifestations of distal respiratory tract infection are attributable to bacterial infection causing inflammation of the airways. Further studies are warranted to pursue more-sensitive methods for detection of viral antigen or antibody in undifferentiated distal respiratory tract disease episodes in foals.

Epidemiologic relations were evaluated between plasma concentrations of nutrients and cardiovascular diseases. A total of 220 cats were assessed: 144 cats with noninduced acquired heart disease and 76 clinically normal cats. Plasma was assayed for taurine, alpha-tocopherol, selenium, retinol, and total cholesterol and triglycerides concentrations. Cardiovascular disease groups included dilated cardiomyopathy (n = 53), left ventricular hypertrophy (n = 28), hyperthyroidism (n = 11), and uncertain classification (n = 52). In cats with dilated cardiomyopathy, mean plasma taurine concentration was the lowest of that in cats of any group, being only 38% of the value in healthy cats; females had less than half the mean value of males. Tocopherol concentration was 20% lower than normal, and retinol concentration was 40% higher than normal. Total cholesterol concentration was 36% lower than normal. Triglycerides concentration was higher in these cats than in any other group-twice the value recorded in healthy cats and 67% higher than that in hyperthyroid cats. In cats with hypertrophic cardiomyopathy, almost 15% had mean plasma taurine concentration < 30 micromol/L. Retinol concentration was 15% higher, and triglycerides concentration was 54% higher than normal. Approximately 27% of hyperthyroid cats had mildly decreased plasma taurine concentration. Hyperthyroid cats had the lowest tocopherol and cholesterol values; both were at least 30% lower than normal. Retinol concentration was 30% higher than Approximately 14% of cats with uncertain classification had mildly decreased plasma taurine concentration. Plasma retinol and triglycerides concentrations were higher than normal in 25 and 38% of these cats, respectively. Plasma selenium concentration, compared between healthy cats and cats with cardiac disease, was not significantly different. This observation may not be meaningful, however, in light of the limited number of cats in which selenium was assessed. Although significant correlation was not observed between plasma taurine and plasma retinol, tocopherol, or cholesterol concentrations in cats with cardiac disease, plasma tocopherol and cholesterol values were highly associated (P < 0.01). Also, the molar ratio of cholesterol to tocopherol was significantly (P < 0.05) lower in cats with dilated cardiomyopathy, compared with healthy cats.

Female Sprague-Dawley rats were treated IM with 0, 2.5, 25, and 50 micrograms of clenbuterol HCl/kg of body weight/d for 21 days. In all treated rats, significant increase in body weight gain (P < 0.05) and improvement in feed conversion ratio (P < 0.05) were recorded. Hydrometra was observed in the uterus of treated rats, and histologically, it was possible to see dilatation of luminal glands and ovarian alterations. Clenbuterol treatment induced significant (P < 0.05) increase in uterine estrogen receptor concentration of rats treated with the 2 higher doses. Treatment apparently failed to enhance the rate of oxidative and conjugative biotransformations, except for glucuronidation of p-nitrophenol (P < 0.05). On the basis of the data obtained, we could affirm that high doses of clenbuterol affect the female reproductive system of rats inducing, almost in part, estrogen-like modifications, but probably by a different mechanism of action correlated to intense adrenergic stimulation.

Clinically normal dogs were evaluated in states of dehydration, euhydration, and after fluid administration to determine effects of hydration state on renal clearance values. Endogenous creatinine, exogenous creatinine, and [(14)C]inulin clearances, were determined to measure glomerular filtration rate (GFR); in some experiments p-aminohippurate clearance was determined to measure renal plasma flow. Dehydration caused significant (P < 0.05) decrease in clearance values, compared with euhydration, and clearance values during euhydration were significantly (P < 0.05) less than values obtained after a single gavage with water (30 ml/kg of body weight). Sustained administration of 3 fluid regimens was evaluated for effects on clearance values (treatment A = 30 ml of lactated Ringer's solution/kg/h; treatment B = 30 ml of water/kg by gavage hourly; treatment C = 10 ml of glucose:lactated Ringer's solution/ kg/h). All regimens of fluid therapy caused significant P < 0.05), progressive increases in GFR, but treatment C resulted in the most stable GFR values. Increases in clearance values were associated with positive fluid balance; the rate of fluid administration was greater than the rate of urine formation. Data from 285 GFR determinations on 85 dogs were evaluated retrospectively. For each determination, three 20-minute urine collections were made beginning 40 minutes after 30 mi of water/kg was given by gavage. Values between collections were significantly (P < 0.05) different, but varied by < 3%. Comparison of methods for measurement of GFR indicated that endogenous creatinine clearance and [14)C]inulin clearance were highly correlated (R(2) = 0.82), but mean clearance values were markedly different (mean +/- SEM, 28.70 +/- 0.01 and 37.07 +/- 1.29 ml/min, respectively). Exogenous creatinine clearance and [(14)C]inulin clearance were highly correlated (R(2) = 0.95), and mean values were 40.54 +/- 0.70 and 41.02 +/- 0.70 ml/min respectively. We conclude that: state of hydration has a marked effect on GFR; rate of fluid administration that exceeds rate of urine production results in progressive increases in GFR; a single water gavage of 30 ml/kg gives stable GFR values for three 20-minute collection periods, may avoid subclinical states of dehydration, and facilitates accurate urine collections; and endogenous creatinine clearance, as conducted in this study, does not accurately measure GFR.