Enrofloxacin and marbofloxacin in horses: comparison of pharmacokinetic parameters, use of urinary and metabolite data to estimate first-pass effect and absorbed fraction.

Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections in horses. A repeated measures study has been designed to compare their pharmacokinetic parameters, to investigate their bioavailability and to estimate their absorbed fraction and first-pass effect by using plasma, urinary and metabolite data collected from five healthy mares. Clearance and V(d(ss)) were greater for enrofloxacin (mean +/- SD = 6.34 +/- 1.5 mL/min/kg and 2.32 +/- 0.32 L/kg, respectively) than for marbofloxacin (4.62 +/- 0.67 mL/min/kg and 1.6 +/- 0.25 L/kg, respectively). Variance of the AUC(0-inf) of marbofloxacin was lower than that for enrofloxacin, with, respectively, a CV = 15% and 26% intravenously and a CV = 31% and 55% after oral administration. Mean oral bioavailability was not significantly different between marbofloxacin (59%) and enrofloxacin (55%). The mean percentage of the dose eliminated unchanged in urine was significantly higher for marbofloxacin (39.7%) than that for enrofloxacin (3.4%). Absorbed fraction and first-pass effect were only determinable for enrofloxacin, whereas the percentage of the dose absorbed in the portal circulation was estimated to be 78% and the fraction not extracted during the first pass through the liver was 65%. Consequently, the moderate observed bioavailability of enrofloxacin appears to be mainly caused by hepatic first-pass effect.

Respiratory and metabolic effects of massive administration of isotonic saline solution in heaves-affected and control horses.

REASONS FOR PERFORMING STUDY: It has been suggested that rapid administration of isotonic saline solution relieves airway obstruction in heaves-affected horses, but the efficacy and tolerability of this treatment is poorly documented. OBJECTIVES: To determine the respiratory and metabolic effects of a rapid administration of isotonic saline solution in control horses and those with heaves. METHODS: Thirty litres isotonic saline solution were administered i.v. to 5 control (Group C) and 9 heaves-affected horses (Group H). Pulmonary function testing and arterial blood gas analysis were performed prior to saline infusion, at 90 and 180 mins after starting the infusion, and 1, 3, 6 and 10 days later. PCV, plasma total solids, plasma electrolytes (Na+, Cl- and K+) and venous blood gas analysis were performed prior, during and after saline infusion. RESULTS: Rapid saline administration was shown to have no beneficial effects on lung function during infusion in Group H. On the contrary, they had significantly increased pulmonary resistance (RL) at 180 mins following the initiation of saline administration compared to baseline. In Group C, saline administration resulted in a significant increase in RL at 180 mins and a significant decrease in PaO2 at 90 mins. These results suggest a transient decrement in lung function caused by rapid saline administration. Group H had a metabolic alkalosis with hypochloraemia at baseline compared to control horses. This resolved following i.v. saline administration and returned to baseline within 6 h after treatment had been discontinued. CONCLUSION: The administration of saline to Group H did not improve airway function significantly, but resulted in mild and transient side effects. POTENTIAL RELEVANCE: Rapid administration of isotonic saline alone is not an effective therapy for heaves in horses.

Population pharmacokinetics of marbofloxacin in horses: preliminary analysis.

Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance for diseased horses than healthy horses, with respectively a mean of 0.209 and 0.284 L/h/kg and a coefficient of variation of 52 and 15%. Consequently, variability of AUC was greater in diseased horses. Considering an AUC/MIC ratio below 60 h as a prediction of poor efficacy, a dosage regimen of 2 mg/kg intravenous was deemed to be inadequate for 19% of diseased horses if the MIC of the bacteria was 0.1 microg/mL. However 93% of diseased horses could achieve a ratio above 125 h, predicting a very good efficacy, for the MIC(90) of Enterobacteriacae (0.027 microg/mL).

Monthly, daily, and circadian variations of measurements of pulmonary mechanics in horses with chronic obstructive pulmonary disease.

OBJECTIVES: To determine temporal variations of pulmonary function in horses without respiratory tract disease (controls) and horses with chronic obstructive pulmonary disease (COPD) and determine whether reversibility of airway obstruction after environmental control can be predicted by response to atropine administration. ANIMALS: 7 COPD-affected and 5 control horses. PROCEDURES: Pulmonary function testing was performed monthly during 3 consecutive months, daily for 5 consecutive days, and at 6-hour intervals for 24 hours before and after administration of atropine (0.02 mg/kg of body weight, i.v.) and after 5 consecutive months at pasture. Respiratory rate, tidal volume (VT), minute ventilation (VE), maximal change in transpulmonary pressure (deltaP(L)), pulmonary resistance (R(L)), and pulmonary elastance (E(L)) were calculated. RESULTS: COPD-affected horses had a significantly higher expiratory to inspiratory time ratio (T(E)/T(I)) and deltaP(L), E(L), and R(L) than horses without respiratory tract diseases during all periods and higher V(E) during monthly and daily evaluations. Daily variation in VT and monthly and circadian variation in E(L) were significant in COPD-affected horses. In control horses, significant changes were apparent only in T(E)/T(I) during daily recordings. In COPD-affected horses, reduction in deltaP(L), R(L), and E(L) was significant after atropine administration and after maintenance on pasture. CONCLUSIONS AND CLINICAL RELEVANCE: Despite variations in measurements of respiratory mechanics in both groups of horses, values remained significantly different between groups over time. Despite individual variation, measurements were repeatable during short and long periods. Response to administration of atropine to COPD-affected horses underestimated improvement in respiratory tract function that resulted from maintenance on pasture.

Effects of inhaled beclomethasone dipropionate on respiratory function in horses with chronic obstructive pulmonary disease (COPD).

The effects of beclomethasone dipropionate on pulmonary function and arterial blood gas values were investigated in horses with chronic obstructive pulmonary disease (COPD). Six mature mares, diagnosed as having COPD based on clinical signs, cytological examination of bronchoalveolar lavage and pulmonary function testing, were used. Beclomethasone dipropionate (3750 microg) was administered b.i.d. for a 2 week period with a metered dose inhaler using a mask. Pulmonary function tests and arterial blood gas analyses were performed at weekly intervals, starting before beclomethasone administration and for 4 weeks thereafter. Upper airway endoscopy and nasopharyngeal fungal cultures were performed before and after treatment. Maximal variations in transpulmonary pressure (deltaPL) were elevated in all horses at baseline. Beclomethasone administration resulted in a significant decrease in deltaPL in 5 horses, and deltaPL fell to within the normal range in 4 horses. Two weeks after the end of treatment, deltaPL was at or above baseline values in all horses. Total pulmonary resistance and elastance decreased significantly during treatment and returned to or above baseline values after the administration of beclomethasone was discontinued. At baseline, PaO2 range was 53-90 mmHg. In 4 horses with pronounced laboured breathing, PaO2 increased with treatment. One horse became reluctant to inhale the beclomethasone after one week, and only a transient improvement in respiratory function was noted in this animal. One horse developed a mild lower airway infection 24 h after the beginning of treatment, but no other possible side effects were noticed. Pharyngeal fungal cultures were negative before and after treatment. It can be concluded from the results of this study that inhaled beclomethasone dipropionate causes a marked improvement of respiratory function in horses with COPD.

A survey of exercise-induced pulmonary haemorrhage in Quebec standardbred racehorses.

Sixty Standardbred horses, aged 3 to 10 years, were examined endoscopically for exercise-induced pulmonary haemorrhage (EIPH) 1 h after racing, on at least 3 occasions. Racing time, finishing position and post exercise venous lactate concentrations were also recorded. Horses positive for tracheal blood on endoscopy were classified as having either grade 1 EIPH (one or a few spots of blood in the trachea), or grade 2 (stream of blood). Air temperature, relative humidity and air pollutant levels were recorded on each examination day. Of the 60 horses, 52 (87%) were EIPH-positive on at least one evaluation out of 3 and 40 of the 52 (77%) showed grade 2 EIPH on at least one occasion. Of the 52 EIPH-positive horses, 52% bled 3 times out of 3, 21% 2 out of 3 and 27% once. When only the first examination was considered, 37 of the 60 horses (62%) were EIPH-positive. There was no significant relation detected between either presence or frequency of EIPH and age, sex, or gait. Horses that showed grade 2 EIPH bled significantly (P = < 0.001) more frequently (mean: 83% of examinations) than horses having shown no more than grade 1 EIPH (47% of examinations). No significant differences could be detected between EIPH-positive and EIPH-negative races in the average racing times, finishing positions and blood lactate concentrations of the 29 horses which showed intermittent EIPH. The proportion of horses showing EIPH on each day where at least 5 horses were examined was correlated with air temperature, relative humidity, and the levels of several air pollutants on those days.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of centrifugation and specimen preparation technique on bronchoalveolar lavage analysis in horses.

Bronchoalveolar lavages (BAL) were performed for 6 healthy horses and 8 horses with lower airway diseases (LAD). Total cell and differential counts were performed before and after centrifugation and resuspension of the BAL cells in a small volume of fluid; there was no difference in the total cell counts, but mast cell percentages were significantly (P < 0.05) lower, after centrifugation, in the LAD group. The two specimen preparation techniques compared were cytocentrifugation and centrifugation on microscope glass covers. For both groups of horses, lymphocyte percentages were significantly lower on cytocentrifuged specimens; there was also an increase in the other predominant cell type, i.e. macrophages in healthy horses and neutrophils in horses with LAD. Lymphocyte percentages in healthy horses were higher than those reported in previous studies, possibly because of a long-standing exposure to a high-dust environment. This study suggests that one centrifugation of the BAL fluid does not affect total cell counts, but may cause a decrease in mast cell percentage; cytocentrifugation is associated with a consistent decrease in lymphocyte percentage.

Effects of triamcinolone acetonide on pulmonary function and bronchoalveolar lavage cytologic features in horses with chronic obstructive pulmonary disease.

Effects of triamcinolone acetonide (TA) on pulmonary function, bronchoalveolar lavage cytologic features and serum cortisol concentration, were studied in 5 control horses and 5 horses with chronic obstructive pulmonary disease (COPD). In experiment 1, horses were brought in from pasture 3 weeks before administration of 1 injection of TA (0.09 mg/kg of body weight, IM), and were stabled in dusty conditions throughout the experimental period. Measurements of respiratory rate (f), tidal volume, minute ventilation, expiratory-to-inspiratory time ratio, maximal change in transpulmonary pressure (delta PL), pulmonary resistance (RL), and dynamic compliance (Cdyn) were obtained during quiet breathing, immediately before (baseline) and 1, 2, 3, 5, and 9 weeks after administration of TA. Pulmonary airway cells were collected by bronchoalveolar lavage while horses were at pasture, at baseline, and 2, 5, and 9 weeks after TA administration. Serum cortisol concentration was measured before and after adrenocortical stimulation with 100 IU of adrenocorticotropic hormone, 1 week prior to TA administration, and 4 and 8 weeks thereafter. In experiment 2, 4 months after TA injection, pulmonary function measurements were repeated in all horses immediately before and 30 minutes after administration of atropine (0.015 mg/kg, IV), to evaluate the reversibility of airway obstruction. In experiment 1 at baseline, COPD-affected horses had significantly (P < 0.05) higher values than did controls for f, delta PL, RL, and percentage of neutrophils, and had lower values for Cdyn and percentage of lymphocytes and macrophages. There was significant reductions in delta PL and RL, and increase in macrophage percentage after TA administration in COPD-affected horses only.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of stabling on bronchoalveolar cells obtained from normal and COPD horses.

Bronchoalveolar lavages (BAL) were performed before and after 3 weeks of housing in 5 horses suffering from COPD and 5 normal horses. In the two groups, the total number of cells recovered remained unchanged after stabling. The most common cell populations in BAL fluid of control animals were alveolar macrophages (46.4%) and lymphocytes (44.9%). The percentage of neutrophils increased after stabling from 8.7% to 27.6%. In COPD horses, lymphocytes predominated (40.7%) in animals at pasture with neutrophils increasing from 29.4% to 71.6% after stabling. After fractionation by Percoll density gradient, alveolar macrophages and neutrophils from normal and COPD horses had a similar density distribution. After stabling, these cells from normal horses were increased in the low density layers, while those from COPD horses were predominantly in the hyperdense layers. Therefore, BAL cells obtained from COPD animals at pasture and after stabling differ from those of control horses in the same environment, not only in their populations but also in their buoyant densities. These differences could be related to different states of cellular activation and perhaps be responsible for disease activity in the COPD horses.

A retrospective study of bronchoalveolar lavage cytology in horses with clinical findings of small airway disease.

A retrospective of 69 bronchoalveolar lavages (BAL) on horses was done to investigate the relationship between bronchoalveolar cell types and clinical signs in horses with small airway disease. Horses were grouped according to clinical findings. The groups were as follows: I. cough only (n = 14), II. cough with mucopurulent secretions in the trachea (n = 14), III. cough, mucopurulent secretions in the trachea and abnormal lung sounds (n = 24) and IV., all of the above plus dyspnea at rest (n = 17). An asymptomatic group was formed from horses in the same population to serve as control (n = 8). There was a significant difference between cytological profiles of asymptomatic horses and the symptomatic group horses, indicating that BAL findings are different when clinical manifestations of the disease are present. Furthermore, neutrophil counts increased as the severity of clinical signs increased from group I to IV. Some variations of other cell types such as mast cells were also reported. Though a significant increase in neutrophils was predictable in dyspneic horses, there was an absence of typical cytological pictures for the other symptomatic but non-dyspneic groups of horses. This study concludes that BAL is a useful diagnostic tool which allows further characterisation of inflammatory processes when clinical signs if small airway disease are apparent.

Histamine inhalation challenge in normal horses and in horses with small airway disease.

A histamine inhalation challenge (HIC) procedure was developed to assess hyperreactive states in horses. Following clinical evaluation, percutaneous lung biopsies were performed on nine light breed mares aged 6 to 15 years. Five horses, with normal small airways, were classified as group A and four subjects with small airway disease (SAD) lesions formed group B. Pulmonary mechanics parameters were monitored following an aerosol of 0.9% saline and every 5 min for up to 30 min after HIC with 0.5% w/v of histamine diphosphate, administered through a face mask for 2.5 min. Tidal volume (VT) and airflow (V) values were obtained with a pneumotachograph. Transpulmonary pressure (delta Ppl) was measured by the esophageal balloon catheter method. Dynamic compliance (Cdyn), total pulmonary resistance (RL), end expiratory work of breathing (EEW) and respiratory rate (f) were calculated by a pulmonary mechanics computer. Group A horses had increases in RL, and decreases in Cdyn whereas horses in group B were hyperreactive and showed greater changes in EEW, Cdyn, and delta Ppl but with a relatively lower variation of RL. One horse in clinical remission from SAD, but with a high biopsy score (group B), and one clinically normal horse belonging to group A showed marked hyperreactivity as shown by increases in EEW, maximum change in delta Ppl and RL and decreases in Cdyn. These results suggest that the HIC described can be used as a method to investigate airway hyperreactivity and SAD in horses.

Use of a protected catheter brush for culture of the lower respiratory tract in horses with small airway disease.

A protected catheter brush introduced by fiberoptic bronchoscopy was used to sample the tracheai and bronchial mucosa in 28 horses with small airway disease. Tracheal and bronchial brushings were examined for the presence of fungi, aerobic and anaerobic bacteria, and a cytoiogical evaluation was also done on fluid collected by the bronchoalveolar lavage (BAL) technique. Microorganisms (bacteria and fungi) were isolated more often in tracheal brushings (53.6%) than in bronchial brushings (10.7%). Anaerobic bacteria were not isolated. Results of this study indicate that fiberoptic bronchoscopy using a protected catheter brush is an easy and practical technique to obtain minimally contaminated samples for isolation of microorganisms from the lower respiratory tract of horses. However, no association was observed between isolation of high numbers of microorganisms from the bronchi and severity of small airway disease.

Radioimmunoassay of serum pepsinogen in relation to gastric (pars oesophagea) ulceration in swine herds.

A radioimmunoassay for the detection of serum swine pepsinogens is described. The sensitivity and reproducibility of the assay were satisfactory for its clinical use. In normal pigs, the serum pepsinogen level was 1.51 +/- 0.56 ng/mL. Cases with parakeratosis, erosions and ulcerations of the pars oesophagea had elevated pepsinogen levels (5.15 +/- 1.98 ng/mL).

A retrospective study of nineteen ataxic horses.

A retrospective study of 19 ataxic horses admitted to the College of Veterinary Medicine of the University of Montreal during the period of January 1985 to December 1988 is presented. There were 11 cases of cervical vertebral malformation, four of equine degenerative myeloencephalopathy, two of equine protozoal myeloencephalitis, one each of vertebral osteomyelitis and intervertebral disc protrusion. The clinical diagnosis of ataxia in horses requires neurological, radiographic, myelographic, and laboratory examinations.

Comparison of the bacterial and fungal flora in the pharynx of normal horses and horses affected with pharyngitis.

A total of 43 horses were used for the study of the pharyngeal bacterial flora. The median value of the number of bacteria in the group of 19 normal horses was 3.8 x 10(4) cfu/g of secretions. This value was 6.4 x 10(4)cfu/g in horses with grade I pharyngitis, 1.3 x 10(5) cfu/g in horses with grade II pharyngitis and 3.5 x 10(6) cfu/g in horses affected with grades III and IV pharyngitis. Corynebacterium spp, coagulase-negative staphylococci, Nocardia spp, Moraxella spp and Enterobacter spp were the most frequently encountered bacteria in the normal animals as well as in horses affected with pharyngitis of grades I or II. Moraxella spp were isolated in 87.5% of the horses with pharyngitis of grades III and IV, followed by Streptococcus zooepidemicus, Pseudomonas aeruginosa, coagulase-negative staphylococci and Enterobacter spp. No fastidious bacteria, nor strict anaerobes were isolated from any of the 43 horses. None of the microorganisms were found in 100% of the animals and the majority of the isolates were opportunistic bacteria. These results demonstrate that the isolation of Moraxella spp and S. zooepidemicus in large numbers is frequent in horses with lymphoid follicular hyperplasia grades III and IV. Fungi were isolated in small numbers from two or three horses in each group.

Diverticulum and fistula of the lower cervical esophagus in a horse.

Esophageal diverticulum and perforation were diagnosed in a horse. The condition was characterized clinically by dysphagia, polypnea, diffuse swelling of the ventral aspect of neck and cutaneous fistula. Endoscopic examination revealed the presence of food material in the guttural pouch. A barium sulfate esophagram was performed to outline the diverticulum.Exploratory surgery confirmed esophageal perforation and entrapment of food material between the muscular planes of the cervical region and the horse was euthanized. At necropsy a food-filled periesophageal tract was found extending from the esophageal rupture to the left guttural pouch.