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Summary

Pulmonary function measurements were made in control ponies and in ponies with recurrent obstructive pulmonary disease (principals) during clinical remission and during an attack of acute airway obstruction. The ponies were given β-adrenergic antagonists and agonists to determine the role of β receptors in recurrent obstructive pulmonary disease, and to determine the subtypes of β receptors mediating bronchodilation in ponies. Aerosol administration of the β antagonists, propranolol (β1 and β2), atenolol (β1), and butoxamine (β2) decreased dynamic compliance (Cdyn) and increased pulmonary resistance (RL) in the principal ponies during airway obstruction, but were without effect when the ponies were in clinical remission. Intravenous administration of atropine reversed the effect of atenolol on Cdyn and RL, but was without effect on the decrease in Cdyn and increase in RL observed after butoxamine administration. The β antagonists did not affect airway function in the control ponies. The effect of β blockade on Cdyn and RL suggests β-adrenergic activation in the central and peripheral airways of principal ponies, mediated through both β2- and β1-adrenergic receptors. The aerosol β agonists, isoproterenol (β1 and β2), and clenbuterol (β2) attenuated histamine-induced airway obstruction to a similar extent in control ponies that were given histamine iv. In addition, the β1 antagonist, atenolol, did not attenuate the bronchodilation observed with isoproterenol. We concluded that, although β1- and β2-adrenergic receptors exist in pony airways and are activated during acute airway obstruction, bronchodilation in response to β agonists in ponies seems to be mediated primarily by β2-adrenergic receptors.

Free access
in American Journal of Veterinary Research

Summary

Distal airway segments (id, 3 to 4 mm; length, 5 mm) from 2 groups of horses were isolated and suspended in tissue baths filled with Krebs solution, aerated with 5% CO2 in oxygen and maintained at 37 C. Responses to exogenous acetylcholine, isoproterenol, or electrical field stimulation were compared. Control horses (n = 30) had no history of recurrent airway obstruction, whereas principal horses (n = 15) had recurrent airway obstruction and were studied during an acute episode of airway obstruction. Although the distal airways contracted in response to the cumulative half-logarithmic addition of acetylcholine (10-10 M to 10-3 M) in both groups, bronchi obtained from principals were less sensitive to acetylcholine than were bronchi obtained from controls. Tetdrodotoxin-sensitive electrical field stimulation-induced contractions were observed in both groups of airways, but the tension achieved in principal bronchi was less than in controls. All electrical field stimulation-induced contractions were abolished by atropine, indicating that the only excitatory innervation of equine distal airways is through the parasympathetic system. To examine the effect of isoproterenol and determine inhibitory innervation, bronchi were precontracted with histamine. Electrical field stimulation did not cause relaxation of precontracted bronchi in either group, thus indicating that distal airways lack inhibitory innervation. Isoproterenol caused similar, dose-dependent relaxation in both groups.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine the dose of aerosolized albuterol sulfate required to cause bronchodilation in horses with recurrent airway obstruction (RAO) and duration of this effect.

Animals

19 horses with RAO (10 in experiment 1; 9 in experiment 2).

Procedure

Horses were moved from pasture to stables, and airway obstruction was induced. Pulmonary function was measured in 10 horses before and 5, 10, and 30 minutes after administration of vehicle or 120, 240, 360, or 720 µg of the drug. Nine horses received vehicle or 360 or 720 µg of albuterol, and pulmonary function was measured at baseline and 5 minutes and 1, 2, 3, 4, 5, 6, and 7 hours later. Horses were evaluated for adverse drug effects.

Results

360 µg of albuterol was required to cause significant bronchodilatation; 720 µg did not enhance bronchodilatation or increase duration of action. Depending on which pulmonary function parameter was evaluated, bronchodilatation achieved by use of albuterol lasted between 30 minutes and 1 hour. Because there was a significant vehicle effect, the combined effect of vehicle and drug lasted up to 3 hours. Adverse effects were not observed.

Conclusions

Aerosolized albuterol, 360 or 720 µg, is a safe and effective bronchodilator in horses with RAO. Onset of action is rapid (5 minutes), and effects last from 30 minutes to 3 hours.

Clinical Relevance

Aerosolized albuterol is useful for treatment of bronchospasm in horses with RAO. (Am J Vet Res 1999;60:689–693)

Free access
in American Journal of Veterinary Research

SUMMARY

We defined methods for use of luminol-dependent chemiluminescence (ldcl) and superoxide anion (O2 -) production as parameters of the oxidative metabolism of neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how variations in blood sample handling, agonist preparation, individual variability, and age of calves influenced the ldcl and O2 - responses to certain agonists, and defined concentrations of soluble and particulate agonists that maximally stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses, particularly ldcl, were characterized by marked day-to-day variability, differed greatly within and between calves, were partially age-dependent, and were partially dependent on the individual agonist. Superoxide anion production had substantially less variability.

We compared the in vitro oxidative (ldcl and O2 -) responses of neutrophils isolated from neonatal calves stimulated by defined concentrations of the agonists–latex, phorbol myristate acetate, calcium ionophore, and opsonized zymosan–with responses to formylated oligopeptides and zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or nonpathogenic, enhanced the ldcl and O2 - responses of stimulated neutrophils although P haemolytica was a less potent stimulant of oxidative functions than were nonbiological agonists.

We conclude that the generation of reactive oxygen species by bovine neutrophils in response to P haemolytica is highly dependent on the presence of opsonins and is greatly enhanced in live vs killed bacteria. Furthermore, the in vitro generation of reactive oxygen species, including O2 - by stimulated neutrophils, may be of biologic importance if similar events occur in vivo, and could have a major role in the pathogenesis of the acute lung injury associated with pneumonic pasteurellosis.

Free access
in American Journal of Veterinary Research

SUMMARY

Release of enzymes from cytoplasmic granules has been postulated to have a major role in neutrophil-mediated tissue injury. Secretion or release of primary granules, specific granules, and cytosolic enzymes by bovine neutrophils was examined by quantifying the release of β-glucuronidase, B12-binding protein, and lactate dehydrogenase, respectively, in response to predetermined amounts of phorbol myristate acetate, calcium ionophore, and opsonized zymosan. These responses were compared with the enzyme release induced by exposure to live or dead, unopsonized or opsonized Pasteurella haemolytica. The greatest release of β-glucuronidase, B12-binding protein, and lactate dehydrogenase was observed in neutrophils exposed to live organisms partially because of neutrophil lysis. Bovine neutrophils respond markedly to particulate agonists, live or dead, pathogenic or nonpathogenic, by a selective release of specific granules, an effect enhanced by opsonization. Particulate agonists induce minimal primary granule release other than that induced by cell death. Because bovine neutrophils contain quantitatively high numbers of specific granules, the high rate of secretion/release in response to P haemolytica organisms could have a major role in the tissue responses that characterize the lesions of pneumonic pasteurellosis.

Free access
in American Journal of Veterinary Research

SUMMARY

Large colon torsion frequently is a fatal condition in horses. The purpose of the study reported here was to determine systemic arterial pressure, plasma eicosanoid concentrations, colonic blood flow, vascular resistance, tissue pH, and morphologic features associated with large colon torsion and detorsion, and to evaluate the effects of sodium heparin (80 IU/kg of body weight, iv) treatment on these values. Values were determined in 20 anesthetized ponies that were randomly assigned into 4 equal groups: control; control/heparin; torsion; torsion/heparin. Torsions were created by a 720° rotation of the cecum and colon around their long axes at the sternal and diaphragmatic flexures. After 1 hour of torsion, the torsion was corrected and the colon was allowed to reperfuse for 1 hour. Heparin was administered 30 minutes into the experiment. Parametric data were analyzed (P ≤ 0.05), using split-plot analysis of variance, with differences between means evaluated with a modified Bonferroni t test; histopathologic data were analyzed (P ≤ 0.05) with a Kruskal-Wallis one-way analysis of variance by ranks. Heparin prevented colonic detorsion-induced hypotension and increases in vascular resistance and thromboxane concentration, and it significantly increased colonic blood flow for 40 minutes during reperfusion. Heparin did not alter prostacyclin concentration or the histologic appearance of the large colon.

Free access
in American Journal of Veterinary Research

SUMMARY

The effects of exogenous platelet-activating factor (paf) were determined in anesthetized ponies. Administration of paf induced a decrease in cardiac index that resulted in systemic hypotension. This was followed by tachycardia, hypertension, and a return of cardiac index to baseline. Pulmonary aterial pressure increased markedly because of pulmonary vasoconstriction. Exogenous paf also caused leukopenia and thrombocytopenia. The specific PAP receptor antagonist (WEB 2086) blocked all paf-induced changes. Flunixin meglumine, a cyclooxygenase inhibitor, abolished the pulmonary hypertension and tachycardia, and attenuated the systemic hypotension but did not change the paf-induced peripheral cellular changes. The paf antagonist also inhibited platelet aggregation induced by paf in vitro. The paf-induced changes are similar to those reported after endotoxin exposure in horses.

Free access
in American Journal of Veterinary Research

Summary

The efficacy of a nerve muscle pedicle (nmp) graft in restoring upper airway function was evaluated in exercising horses with induced left laryngeal hemiplegia. The nmp graft was created from the first cervical nerve and the omohyoideus muscle and transplanted into the left cricoarytenoideus dorsalis muscle. Seven adult Standardbreds were trained to exercise on a treadmill inclined at 6.38°. With the horses at rest and exercising at 4.2 and 7.0 m/s, the following variables were recorded: peak inspiratory and expiratory transupper airway pressures (defined as the pressure difference between a lateral tracheal catheter and a mask catheter), peak inspiratory and expiratory air flow, inspiratory and expiratory impedance, tidal volume, minute ventilation, heart rate, and respiratory frequency. Measurements were made before left recurrent laryngeal neurectomy (lrln), 28 days after lrln, and 12, 24, and 52 weeks after the nmp graft (n = 5) or sham operation (n = 2). Before lrln, exercise increased inspiratory and expiratory air flow and transupper airway pressure, whereas the impedance was unchanged. After lrln, transupper airway inspiratory pressure and impedance were significantly greater and inspiratory air flow was significantly less than baseline values at 7.0 m/s. The sham operation did not improve airway function. Twelve weeks after insertion of the nmp graft, inspiratory impedance and inspiratory air flow were significantly different (improved) from lrln values. Twenty-four weeks after insertion of the nmp graft, inspiratory impedance was not significantly different from lrln values. Fifty-two weeks after insertion of the nmp graft, inspiratory impedance was not significantly different from the baseline value and was significantly less than the value after lrln. We conclude that the nerve muscle pedicle graft can restore upper airway function within 52 weeks in horses with induced left laryngeal hemiplegia.

Free access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine whether 2- or 3-times-daily application of topical ophthalmic 0.005% latanoprost solution is more effective at lowering intraocular pressure (IOP) in clinically normal dogs.

ANIMALS 9 clinically normal dogs.

PROCEDURES For each dog, I drop of latanoprost 0.005% solution was applied to 1 eye every 8 or 12 hours each day for 5 days; the contralateral eye received topical ophthalmic treatment with 1 drop of saline (0.9% NaCl) solution at the times of latanoprost application. Ocular examinations of both eyes were performed every 6 hours starting 48 hours prior to and ending 42 hours after the treatment period. Following a 5-week washout interval, the procedures were repeated but the previously latanoprost-treated eye of each dog received latanoprost application at the alternate frequency.

RESULTS Mean ± SD IOP reduction in the latanoprost-treated eyes was 31 ± 6.9% with 2-times-daily application and 33 ± 8.2% with 3-times-daily application. A 2-way repeated-measures ANOVA revealed significant differences in IOP with contributions by treatment (2 or 3 times daily), time of day (diurnal variation), and individual dog. The maximum mean daily IOP reduction in latanoprost-treated eyes was detected on day 3 of latanoprost treatment in each group. Eyes treated 3 times daily had significantly smaller pupil diameter and greater conjunctival hyperemia than eyes treated 2 times daily.

CONCLUSIONS AND CLINICAL RELEVANCE The clinical importance of the ocular hypotensive effects of 3-times-daily topical ophthalmic application of 0.005% latanoprost solution in dogs with glaucoma warrants investigation.

Full access
in American Journal of Veterinary Research