The effects of 2 drugs, xylazine and propofol, on the urethral pressure profile were compared. Seven female dogs were sedated by administration of one drug, then the other, and urethral variables were measured. In the dogs sedated with propofol, the mean +/- SD, maximal urethral closure pressure (51 +/- 7.4 cm of H2O) was significantly (P < 0.05) higher than the value when dogs were sedated with xylazine (23.3 +/- 7.6 cm of H2O). Results were compared with those obtained by various authors, in particular for nonsedated dogs. It is concluded that propofol is a good drug for investigation of the urethral pressure profile, whatever its effect on maximal urethral closure pressure.

Effects of a change from a diet composed primarily of forage to a diet composed primarily of concentrate on abomasal antral and duodenal motility were assessed in 5 lactating Holstein cows. Antroduodenal motility was measured by use of 8 silver electrodes sutured to ther abomasum and duodenum, and abomasal emptying was assesssed by continuous measurement of intraduodenal pH. Both diets were fed to achieve a daily dry matter intake of 2.7 kg/100 kg of body weight. The abrupt change in diet did not alter antoduodenal myoelectric activity or abomasal emptying. Initiation of phase III of the migrating myoelectric complex in the proximal portion of the duodenum corresponded with a decrease in abomasal antral spiking activity and an increase in intraduodenal pH. Results suggest that a high concentrate diet alone does not adversely affect antroduodenal motility in adult dairy cattle.

The objectives of this experiment were to determine serum concentrations of triiodothyronine (T3), thyroxine (T4), and free thyroxine (fT4) at rest, following thyroid-stimulating hormone (TSH) administration, and following phenylbutazone administration in healthy horses. This was done to determine which available laboratory test can best be used for diagnosis of hypothyroid conditions in horses. Serum T3, T4, and fT4 concentrations in serum samples obtained before and after TSH stimulation and following phenylbutazone administration for 7 days were determined. Baseline values ranged from 0.21 to 0.80 ng of T3/ml, 6.2 to 25.1 ng of T4/ml, and 0.07 to 0.47 ng of fT3/dl. After 5 IU of TSH was administered IV, serum T3 values increased to 6 times baseline values in 2 hours. Thyroxine values increased to 3 times baseline values at 4 hours and remained high at 6 hours. Free T4 values increased to 4 times baseline values at 4 hours and remained high at 6 hours. Administration of 4.4 mg of phenylbutazone/kg, every 12 hours for 7 days significantly decreased T4 and fT4 values, but did not significantly affect serum T3 concentrations, It was concluded that a TSH stimulation test should be performed when hypothyroidism is suspected. Measurement of serum fT4 concentrations, by the single-stage radioimmunoassay, does not provide any additional information about thyroid gland function over that gained by measuring T4 concentrations. Phenylbutazone given at a dosage of 4.4 mg/kg every 24 hours, for 7 days did significantly decrease resting T4 and fT4 concentrations, but did not significantly affect T3 concentrations in horses.

Brain capillary function was assessed in 4- to 6-week-old calves given lead acetate (15 mg/kg of body weight) orally for 7 to 8 days. Neurologic signs of lead poisoning included CNS depression, blindness, and hyperesthesia. Brain capillaries were isolated from cerebral cortex of control and lead-treated calves and evaluated for metabolic indicators, ion transport, and prolyl hydroxylase activity. In lead-treated calves, the rate of glucose metabolism was less than half that in controls. Ion efflux of 45Ca or 36Cl from endothelial cell suspensions was not affected by lead treatment. Prolyl hydroxylase activity in endothelium and proline-to-hydroxyproline ratio in endothelial basement membranes were similar in control and lead-poisoned calves. Results indicate that lead may inhibit energy metabolism, but not ion transport or collagen biosynthesis in brain capillaries of calves and, compared with suckling rats, damage to the blood-brain barrier is less important. In calves, neuronal tissue may be the primary target for the CNS effects of lead.

The potential of a gonadotropin-releasing hormone (GnRH) agonist (goserelin acetate), delivered constantly for 28 days via a subcutaneous depot, to induce ovulation in seasonally anestrous mares, was investigated. Two experiments were conducted, in which a range of doses (30 to 240 micrograms/mare/d) was examined. Mares were selected on the basis of lack of substantial follicular development (follicle diameter < 20 mm determined ultrasonically) and low serum concentrations of luteinizing hormone (LH) and progesterone. Constant administration of the GnRH agonist-induced ovulation in anestrous mares, but a dose-response relation was not observed. Furthermore, with identical doses tested in consecutive or alternate years, considerable variation was observed in the ovulatory response. In general, ovulation in all treated mares was accompanied by increased circulating concentrations of LH and a decrease in follicle-stimulating hormone values. Ovulation was preceded by an increase in estradiol and LH concentrations. In mares in which ovulation did not occur, concentration of LH increased during agonist treatment, whereas that of follicle-stimulating hormone either increased or did not change. It was concluded that constant administration of GnRH agonists may induce ovulation in mares during seasonal anestrus; however, percentage of mares ovulating and the lack of reproducibility of effect indicate that this approach is inappropriate for use as a reliable method to manipulate breeding activity in commercial broodmares.

We investigated the effects of a range of IV administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of IV administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of IV administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administration. In the presence of acid-suppressant treatment, plasma gastrin concentration correlated significantly with gastric pH (Spearman's rank correlation coefficient, p = 0.445, P < 0.01), whereas basal pH and plasma gastrin concentration were not correlated. The effect was not great, and a dose-dependency was not found. Intravenously administered omeprazole was subject to two-compartment pharmacokinetics, and there was evidence for saturable steps in the redistribution and elimination phases. Dosage of 0.25 mg/kg induced approximately half-maximal inhibition of basal gastric pH in these ponies and was associated with area under the concentration vs time curve of 0.7 micromoles.h/L, which corresponds reasonably with results of other species. Omeprazole may represent a useful alternative acid-suppressant agent in horses, but further work is required to relate the dose-dependent effects found in this study to well-defined targets of acid suppression in clinical cases.

Twelve healthy dogs were used to determine the cardiorespiratory effects of IV administered ketamine (10 mg/kg of body weight) and midazolam (0.5 mg/ kg). Half the dogs received a ketamine-midazolam combination (K-M) as a bolus over 30 seconds and the other half received the K-M as an infusion over 15 minutes. Induction of anesthesia by use of K-M was good in all dogs. Ketamine-midazolam combination as a bolus or infusion induced minimal cardiorespiratory effects, except for significant (p < 0.05) increases in mean heart rate and rate-pressure product. The increase in heart rate was greater in dogs of the infusion group. Mild and transient respiratory depression was observed in dogs of both groups immediately after administration of K-M, but was greater in dogs of the bolus group than in dogs of the infusion group. Duration of action of K-M for chemical restraint was short. Salivation and defecation were observed in a few dogs. Extreme muscular tone developed in 1 dog after K-M bolus administration.

Cardiopulmonary and behavioral responses to detomidine, a potent alpha 2-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses (mean +/- SD for age and body weight, 6 +/- 2 years, and 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusion 2), 19.1 +/- 5.1 (infusion 3), and 42.9 +/- 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system. Detomidine caused concentration-dependent sedation and somnolence. These effects were profound during infusions 3 and 4, in which marked head ptosis developed and all horses leaned heavily on the bars of the restraining stocks. Heart rate and cardiac index decreased from baseline measurements (42 +/- 7 beats/min, 65 +/- 11 ml.kg of body weight-1.min-1) in linear relationship with the logarithm of plasma detomidine concentration (ie, heart rate = -4.7 [log(e) detomidine concentration] + 44.3, P < 0.01; cardiac index = -10.5 [log(e) detomidine concentration] + 73.6, P < 0.01). Second-degree atrioventricular block developed in 5 of 7 horses during infusion 3, and in 6 of 7 horses during infusion 4. Mean arterial blood pressure increased significantly from 118 +/- 11 mm of Hg at baseline to 146 +/- 27 mm of Hg at infusion 4. Similar responses were observed for mean pulmonary artery and right atrial pressures. Systemic vascular resistance (baseline, 182 +/- 28 mm of Hg.ml-1.min-1.kg-1) increased significantly during infusions 3 and 4 (to 294 +/- 79 and 380 +/- 58, respectively). Plasma atrial natriuretic peptide concentration was significantly increased with increasing detomidine concentration (20.4 +/- 3.8 pg/ml at baseline to 33.5 +/- 9.1 at infusion 4). There were few significant changes in respiration rate and arterial blood gas and pH values. We conclude that maintenance of steady-state detomidine plasma concentrations resulted in cardiopulmonary changes that were quantitatively similar to those induced by detomidine bolus administration in horses.

Pharmacokinetics and recovery characteristics of propofol in Greyhounds and mixed-breed dogs were compared. In all dogs, disposition of propofol was adequately described by a 2-compartment open model, with a rapid distribution phase followed by a slower elimination phase. When findings in Greyhounds were compared with those in mixed-breed dogs, significant differences were observed in mean concentrations of propofol in blood, recovery characteristics, and estimates for apparent volume of distribution, volume of distribution at steady state, and total body clearance. In addition, Greyhounds recovered from anesthesia at higher concentrations of propofol than did mixed-breed dogs. A secondary peak in blood propofol concentration was observed in 8 of 10 Greyhounds and in 5 of 8 mixed-breed dogs. This peak corresponded to the time of return of the righting reflex.

To clarify the oxidant defense functions of reduced glutathione (GSH) in erythrocytes, the effect of GSH deficiency on in vitro oxidant defense was studied, using GSH-deficient sheep erythrocytes (low-GSH cells). The formation of Heinz bodies in low-GSH cells was higher than that in high-GSH cells when the cells were incubated with an oxidant drug, acetyl-phenylhydrazine (APH). Artificial depletion of GSH by 1-chloro-2,4-dinitrobenzene in high-GSH cells resulted in increased Heinz body formation in these cells incubated with APH. Furthermore, high negative correlation was observed between Heinz body formation and GSH content in sheep erythrocytes exposed to APH. These results clearly indicate that erythrocyte GSH is indispensable for erythrocyte defense against oxidative damage induced by APH, and support the previous observations that sheep with low-GSH erythrocytes were more susceptible to oxidative agents than were sheep with high-GSH erythrocytes.