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.

The popular urodynamic technique of stressed urethral pressure profilometry used for investigation of genuine stress incontinence in women was adapted and applied to bitches. The aim was to assess the suitability and reproducibility of the technique in the canine species, and to determine whether differences seen in continent and incontinent women were found in bitches. Resting and stressed simultaneous urethral pressure profiles were obtained for 25 continent and 25 incontinent bitches, the latter diagnosed as having urethral sphincter mechanism incompetence. The stressed urethral pressure profiles were produced by ballottement of the abdomen during catheter withdrawal. The degree of stress induced was consistent and had got short-term reproducibility. Highly significant (P < 0.001) differences in the percentage of negative spikes extending below the resting intravesical pressure were found between continent and incontinent bitches. Significant differences were not observed in the pressure transmission profiles between continent and incontinent bitches; both groups had a gradual decrease in pressure transmission from the bladder neck to the external urethral orifice. The distance from the start of the urethral pressure profile to the first negative peak (attributable to respiration or ballottement) on the subtracted profile was compared with the radiographic distance that the bladder neck was positioned with respect to the cranial pubic brim, taking body weight and continence status into account. Body weight and continence status did not have significant effect on the relation in either instance. The distance between the start of the urethral pressure profile and the first negative peak induced by respiration was significantly (P < 0.05) related to the bladder neck position with respect to the cranial pubic brim, although it accounted for little of the total variance. Relation between the same variables during stressed urethral pressure profilometry, induced by abdominal ballottement, was not significant.

Clinical findings indicate that canine eyes tolerate implantation of polymethylmethacrylate (PMMA) intraocular lenses (IOL) well, although inflammation and ocular damage attributable to the implants is not known. The use of silicone or polyhydroxyethylmethacrylate (HEMA) IOL has not been reported in dogs. In this study, 15 conditioned, mixed-breed dogs were allotted to 3 groups: 5 received PMMA IOL; 5 received silicone IOL; and 5 received HEMA IOL. The IOL optic was inserted into the anterior chamber of the right eye and anchored to the cornea. An identical surgical procedure was done on the left eye, except that no lens optic was inserted. Clinical examination and measurement of corneal thickness were done immediately prior to and after surgery. Aqueous humor samples were collected at the time of surgery and 28 days after surgery. Only mild and transient inflammation was observed in IOL-implanted eyes. On several postoperative days, it was found that PMMA IOL induced significantly greater corneal thickness, aqueous flare, anterior uveal irritation, and corneal edema than did other IOL. Significantly more anterior uveal irritation and increased aqueous humor protein concentration was observed with HEMA IOL than with PMMA or silicone IOL. Silicone IOL induced significantly less fibrin deposition than did PMMA or HEMA IOL.

Ground reaction force (GRF) patterns from 20 clinically sound Dutch Warmbloods were recorded at the right fore-leading canter, and a standard horse was composed. These GRF data for the standard can be used for evaluation of jumping horses. The GRF patterns were asymmetric for all 4 limbs. The leading right forelimb decelerated the body. The trailing left forelimb propelled the body and decelerated it slightly. The trailing left hind limb propelled, and the leading right hind limb contributed to deceleration and propulsion. Referred to the maximal vertical load of the leading right forelimb, the load of the trailing left forelimb was 25% more; the load of the right hind limb was slightly less, whereas the load of the left hind limb was about 80% of that value.

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.

Changes in lateral cecal arterial blood flow, mean internal carotid arterial pressure, and heart rate caused by nasogastric administration of fenoldopam (3, 6, and 9 mg/kg of body weight), a selective agonist of dopaminergic receptors, were recorded in 7 healthy horses. Cecal arterial blood flow was significantly increased within 30 minutes after administration of fenoldopam at all 3 dosages, with the peak increases from baseline (67.8 +/- 17.5 ml/min) being 125 +/- 28, 120 +/- 22, and 153 +/- 32 ml/min for 3, 6, and 9 mg/kg, respectively. Although carotid arterial pressure did not change significantly after administration of fenoldopam at the dosage of 3 mg/kg, administration of fenoldopam at the dosages of 6 and 9 mg/kg significantly reduced carotid arterial pressure from 113 +/- 10 to 88 +/- 3 and 81 +/- 5 mm of Hg, respectively. Intravenous infusion of metoclopramide, a dopaminergic receptor antagonist, at the rate of 0.125 mg/kg/h, blocked the effect of fenoldopam on cecal arterial blood flow and carotid arterial pressure. It was concluded that dopaminergic receptors mediate alterations in local blood flow and systemic pressure in horses.

We determined whether administration of cisplatin in hypertonic saline solution would prevent significant decrease in renal function, as measured by exogenous creatinine clearance, in healthy dogs. A single dose of cisplatin (70 mg/m2 of body surface) was mixed in 3% saline solution and was infused IV (6.5 ml/kg of body weight) over a 20-minute period to 6 healthy dogs. Exogenous creatinine clearance was determined prior to treatment of dogs with cisplatin and again on days 3 and 21 after administration of cisplatin. All 6 dogs vomited at least once within 12 hours of treatment with cisplatin; however, clinically important changes in appetite, body weight, or hydration status were not apparent during the 21-day study. Although mean values for exogenous creatinine clearance decreased from baseline on days 3 and 21, changes were not significantly different. Renal histologic lesions included mild, chronic, lymphoplasmacytic interstitial nephritis in 5 dogs, and presumably, were unrelated to treatment with cisplatin. Mild renal tubular atrophy (n = 2) and tubular necrosis (n = 1) may have developed secondary to treatment with cisplatin. Results of this study indicated that administration of a single dose of cisplatin in 3% saline solution to healthy dogs was not associated with significant decrease in glomerular filtration rate. This is a convenient protocol for administering cisplatin; however, additional study is required before it can be recommended for clinical patients, especially those with preexisting renal disease or those receiving multiple doses of cisplatin.

The role of platelet-activating factor in mediating the cardiovascular and peripheral cellular responses to large-colon ischemia and reperfusion, was explored in anesthetized ponies. A specific platelet. activating factor (PAF) antagonist (WEB 2086) was administered to a group of 6 ponies, and another 6 ponies (controls) were given an equivalent volume of saline solution, prior to 1 hour of large-colon torsion. After correction of the torsion, ponies were monitored during the reperfusion period. Significant (P < 0.05) hypotension and metabolic acidosis developed in afl ponies after correction of colonic torsion, cardiac index increased initially, but then decreased significantly (P < 0.05) over the study period. Mean times between correction of torsion and onset of cardiac failure and death were not different between groups. Significant (P < 0.05) thrombocytopenia developed during the reperfusion period in control ponies, but not in WEB-treated ponies. Blood leukocyte concentration in control ponies was more variable and significantly (P < 0.05) decreased immediately upon reperfusion, compared with that in WEB-treated ponies. We conclude that although the cardiovascular responses to colonic ischemia and reperfusion are not prevented by use of a specific PAF-antagonist, specific peripheral cellular responses are mediated by PAF.

Ibuprofen treatment was compared with saline solution treatment in an endotoxin-induced experimental model of bovine mastitis. Acute mastitis was induced in healthy lactating Holstein cows (n = 12) by intrammamary inoculation of 1 mg of Escbericbia coli 026:B6 lipopolysaccharide in a single quarter per cow. Cows were assigned at random to ibuprofen (25 mg/kg of body weight, IV, n = 6) or 0.9% sodium chloride solution control (1.25 ml/kg, IV, n = 6) treatment groups. Ibuprofen or saline solution was administered once, 2 hours after endotoxin administration. The clinical course of endotoxin-induced mastitis and hematologic, clinical biochemical, and plasma mineral changes were monitored and compared between ibuprofen-treated and control cows. Clinical monitoring and blood sample collection were performed at 0, 2, 4, 6, 8, 12, 24, 48, 96, and 192 hours after endotoxin challenge. Rectal temperature and heart and respiratory rates were significantly (P < 0.05) increased in saline treated cows, compared with cows treated with ibuprofen, Blood eosinophil count and serum phosphorus, sodium, and total carbon dioxide concentrations were significantly (P < 0.05) decreased in saline-treated cows, compared with cows treated with ibuprofen. Ibuprofen treatment did not significantly change ruminations per minute, electrical conductivity of milk, quarter size, or quarter inflammation. The remaining hematologic, serum biochemical, plasma mineral, and coagulation values also were not changed significantly in response to ibuprofen treatment. Untoward effects attributed to ibuprofen administration were not observed. These results indicate that ibuprofen may provide empiric relief of clinical signs of coliform-induced mastitis.

Age and species reportedly affect the pharmacokinetic variables of nonsteroidal anti-inflammatory drugs. We determined the effect of age on flunixin pharmacokinetic variables in foals during the first month of life. We also estimated the physiologic activity of the drug in neonatal foals by determining the effect of flunixin on thromboxane production during clotting of blood taken from the foals. Flunixin disposition and clearance were determined after IV administration of 1.1 mg of drug/kg of body weight to 5 healthy foals when they were 24 to 28 hours, 10 to 11 days, and 27 to 28 days old. The area under the curve (2,471 micrograms.min/ml), mean residence time (477 minutes), and zero-time intercept of the elimination phase (4,853 ng/ml) were significantly (P = 0.05) greater, the elimination half-life (339 minutes) and slope of the elimination phase (0.002 L/min) were significantly (P = 0.05) longer, and total body clearance (0.482 ml/min/kg) and zero-time intercept for the distribution phase (2,092 ng/ml) were significantly (P = 0.05) lower at 24 to 28 hours. At each age, a biexponential equation was best fitted to the plasma flunixin concentration from each foal. Thromboxane B2 production during clotting of blood was significantly (P = 0.05) suppressed for 12 hours after flunixin meglumine administration at all ages. Therefore, it appears that although age does alter the disposition and elimination of flunixin in neonatal foals, this effect may be of little consequence because the drug's physiologic activity in foals appears similar to that in mature horses.