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- Author or Editor: Lawrence R. Soma x
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Abstract
Objective
To determine the effects of endotracheal intubation on respiratory mechanics during xylazine sedation and xylazine-diazepam-ketamine anesthesia in adult horses.
Animals
5 healthy adult horses.
Procedure
Measurements were derived from recordings of respiratory gas flow, and transpulmonary and transtracheal pressures. Total pulmonary resistance (RT) was partitioned into upper airway resistance (extrathoracic portion of trachea, larynx, pharynx, nasal cavity, nares; RUA) and lower airway resistance (intrathoracic portion of trachea, bronchi, bronchioles). Baseline measurements were obtained in unsedated horses, after xylazine administration, and following nasotracheal intubation (ID, 18 mm). Measurements were obtained following induction of xylazine-diazepam-ketamine anesthesia and subsequent to endotracheal intubations (ID, 22, 20, and 16 mm). During recovery, horses were nasotracheally intubated (ID, 18 mm). Measurements were obtained upon standing, and repeated after extubation. Data were examined by use of ANOVA with repeated measures.
Results
Significant increases in mean work of breathing (W), RT, and RUA observed with xylazine sedation were variably attenuated by nasotracheal intubation. During xylazine-diazepam-ketamine anesthesia, the highest mean values for W, RT, RUA, transpulmonary and transtracheal pressures developed during nonintubation periods. The magnitudes of resistance and pressure values were inversely proportional to the internal diameter of the endotracheal tube. At recovery, values of the W and all measurements of resistances and pressures were significantly increased, compared with presedation values. Extubation resulted in further increases in these measurements.
Conclusions
Work of breathing in horses is substantially increased when RUA is increased during xylazine sedation and xylazine-diazepam-ketamine anesthesia. Endotracheal intubation reduces W by reducing RUA. (Am J Vet Res 1997;58:641–646)
Abstract
Objective—To compare pharmacokinetics of triamcinolone acetonide (TA) following IV, intra-articular (IA), and IM administration and determine its effect on plasma concentrations of hydrocortisone and cortisone.
Animals—6 Thoroughbreds.
Procedures—TA (0.04 mg/kg) was administered IV, IM, or IA, and plasma TA, hydrocortisone, and cortisone concentrations were determined.
Results—IV administration of TA was fitted to a 2-compartment model. Median distribution half-life was 0.50 hours (range, 0.24 to 0.67 hours); elimination half-life was 6.1 hours (range, 5.0 to 6.4 hours). Transfer half-life of TA from joint to plasma was 5.2 hours (range, 0.49 to 73 hours); elimination half-life was 23.8 hours (range, 18.9 to 32.2 hours). Maximum plasma concentration following IA administration was 2.0 ng/mL (range, 0.94 to 2.5 ng/mL), and was attained at 10 hours (range, 8 to 12 hours). Maximum plasma concentration following IM administration was 0.34 ng/mL (range, 0.20 to 0.48 ng/mL) and was attained at 13.0 hours (range, 12 to 16 hours); concentration was still quantifiable at 360 hours. Hydrocortisone plasma concentrations were significantly different from baseline within 0.75, 2, and 1 hours after IV, IA, and IM administration, respectively, and remained significantly different from baseline at 96 and 264 hours for IV and IA administration. Following IM administration of TA, plasma concentrations of hydrocortisone did not recover to baseline concentrations by 360 hours.
Conclusions and Clinical Relevance—Pharmacokinetics of TA and related changes in hydrocortisone were described following IV, IA, and IM administration. A single administration of TA has profound effects on secretion of endogenous hydrocortisone.
SUMMARY
Effects of furosemide, exercise, and atropine on tracheal mucus transport rate (tmtr) in horses were investigated. Atropine (0.02 mg/kg of body weight) administered iv or by aerosolization significantly (P < 0.05) decreased tmtr at 60, but not at 30 minutes after its administration in standing horses. Furosemide (1.0 mg/kg, iv) did not have any significant effect on tmtr when measured at 2 or 4 hours after its administration in standing horses. Exercise alone or furosemide (1.0 mg/kg, iv) administration followed 4 hours later by exercise did not alter tmtr, compared with values for standing control or exercised horses administered saline solution. Atropine (0.02 mg/kg, iv) administered after exercise significantly (P < 0.05) decreased tmtr, compared with values for no exercise standing controls, for exercise after administration of saline solution, and for furosemide and exercise.
SUMMARY
Naproxen (+6-methoxy- [α-methyl] -2-naphthalene acetic acid) is a nonsteroidal anti-inflammatory drug that is used for the treatment of inflammatory conditions in horses. We developed a model that describes the drug's disposition and renal excretion, including synovial fluid disposition and elimination after iv administration in horses. The plasma disposition, after iv administration of 5 mg/kg of body weight, was described by a two-compartment model; mean ± sd distribution and elimination half-lives were 1.42 ± 0.42 and 8.26 ± 2.56 hours, respectively. Plasma concentration of naproxen after iv administration of 5 mg/kg was 55.3 ± 13.5 and 0.61 ± 0.42 mg/L at 5 minutes and 48 hours after its administration, respectively. Steady-state volume of distribution was 0.163 ± 0.053 L/kg, and area under the plasma concentration time-curve was 372.1 ± 128.2 mg/h/L. The peak synovial fluid concentration of 12.68 ± 12.39 mg/L was measured at 6 hours, and decreased to 0.71 ± 0.38 mg/L at 36 hours after naproxen administration. The decrease of naproxen concentration in synovial fluid paralleled that in plasma. The appearance half-life of naproxen in synovial fluid was 4.64 hours, and the elimination half-life was 6.73 hours. Total body clearance was 0.015 ± 0.006 L/h/kg. The percentage of plasma protein binding was 97.0 ± 2.9% at plasma concentrations between 5 and 100 mg/L. This was significantly (P < 0.05) higher than the percentage of binding at plasma concentrations of 0.5, 1, and 500 mg/L, which was 75.2 ± 11.8%. Most of the drug was excreted as glucuronidated naproxen and unconjugated desmethylnaproxen. The recovery of naproxen and all metabolites in urine at 36 hours was 64.6 ± 7.2% of the total dose. Of this total, 39.6 ± 10.3% and 8.5 ± 7.9% were glucuronidated naproxen and desmethylnaproxen, respectively; 0.3 ± 0.1% and 16.6 ± 7.9% were free naproxen and desmethylnaproxen, respectively.
SUMMARY
Sheets of mucosa from the jejunum of healthy horses were mounted in incubation chambers and bathed with Krebs-Ringer bicarbonate solution. Changes in tissue function and histologic appearance were compared after the following conditions: (1) control conditions for 30 minutes with 95% O2/5% CO2 in the gas phase; (2) same conditions as control, except incubation with superoxide dismutase (300 U/ml) during the last 18 minutes; (3) anoxia for 15 minutes with 95% N2/5% CO2, followed by reoxygenation for 15 minutes; (4) same conditions as 3, except incubation with superoxide dismutase during reoxygenation; and (5) anoxia for 30 minutes. Anoxia reduced the accumulation of radiolabeled l-alanine and caused cell swelling, as indicated by an increase in tissue water and tissue Na contents. Reoxygenation improved the tissue's ability to accumulate l-alanine, but tissue swelling continued after this treatment. Tissue Na content and l-alanine accumulation were restored to control values by reoxygenation with superoxide dismutase in the bathing medium. The grade of structural damage, as indicated by separation of eptihelial cells from villi, was equally severe after all, but control, conditions. Superoxide dismutase had no effect on the tissue control conditions. Results of this study suggest that superoxide radicals are involved in the pathogenesis of reperfusion injury in equine jejunal mucosa and that this may be of clinical importance in cases of small intestinal strangulation obstruction.
Abstract
OBJECTIVE
A retrospective study was conducted to establish the prerace venous acid-base and blood gas values of Standardbred horses at rest using big data analytics.
SAMPLES
Venous blood samples (73,382) were collected during seven racing seasons from 3 regional tracks in the Commonwealth of Pennsylvania. Horses were detained 2 hours prior to race time.
PROCEDURES
A mixed-effects linear regression model was used for estimating the marginal model adjusted mean (marginal mean) for all major outcomes. The interaction between age and gender, track, and the interaction between month, treatment (furosemide), and year were the major confounders included in the model. Random effects were set on individual animal nested within trainer. Partial pressure of venous carbon dioxide (PVCO2), partial pressure of oxygen (PVO2), and pH were measured, and base excess (BE), total carbon dioxide (TCO2), and bicarbonate (HCO3 −) were calculated.
RESULTS
Significant (P < .001) geographical differences in track locations were seen. Seasonal reductions in acid-base values started in January with significant (P < .001) decreases from adjacent months seen in June, July, and August followed by a gradual return. There were significant increases (P < .001) in BE and TCO2 and decreases in PVO2 with age. Significant differences (P < .001) in acid-base values were seen when comparing genders. A population of trainers were significantly different (P < .001) from the marginal mean and considered outliers.
CLINICAL RELEVANCE
In a population of horses, big data analytics was used to confirm the effects of geography, season, prerace furosemide, gender, age, and trainer influence on blood gases and the acid-base profile.
Abstract
Objective—To determine whether prolonged administration of clenbuterol results in tachyphylaxis, specifically regarding its bronchoprotective properties and effect on sweating in horses.
Animals—8 Thoroughbreds with inflammatory airway disease.
Procedures—In a crossover design, horses received clenbuterol (0.8 μg/kg, PO, q 12 h) or placebo for 21 days, with a washout period of ≥ 30 days between the 2 treatments. Airway reactivity was evaluated by use of flowmetric plethysmography and histamine broncho-provocation before (day 0; baseline) and every 7 days after the start of treatment. Sweat function was evaluated via response to epinephrine administered ID before and every 10 days after the start of treatment.
Results—The concentration of histamine required to increase total airway obstruction by 35% (PC35) was significantly reduced during treatment with clenbuterol (mean change, 11.5 mg/mL), compared with during administration of the placebo (mean change, −1.56 mg/mL), with a peak effect at 14 days. Tachyphylaxis was evident by day 21, with 7 of 8 horses having a PC35 below the baseline value (mean change, −0.48 mg/mL), which returned to baseline values during the washout period. No effect of clenbuterol was seen in sweat response to epinephrine administration.
Conclusions and Clinical Relevance—Clenbuterol initially reduced airway sensitivity to inhaled histamine, but tachyphylaxis that resulted in increased airway reactivity was evident by day 21. Although no effects on sweating were detected, the technique may not have been sensitive enough to identify subtle changes. Prolonged administration of clenbuterol likely results in a clinically important reduction in its bronchodilatory effects.
Abstract
Objective—To investigate the pharmacokinetics of fentanyl administered transdermally and IV in sheep.
Animals—21 adult female sheep.
Procedures—Fentanyl was administered IV to 6 healthy sheep. Transdermal fentanyl patches (TFPs) were applied to 15 sheep 12 hours prior to general anesthesia and surgery. Seria blood samples were collected for 18 hours after IV injection and 84 hours after TFP application. Fentanyl concentrations were quantified via liquid chromatography-mass spectrometry, and pharmacokinetic values were estimated.
Results—All sheep completed the study without complications. Following a dose of 2.5g/kg administered IV, the half-life was 3.08 hours (range, 2.20 to 3.36 hours), volume of distribution at steady state was 8.86 L/kg (range, 5.55 to 15.04 L/kg), and systemic clearance was 3.62 L/kg/h (range, 2.51 to 5.39 L/kg/h). The TFPs were applied at a mean dose of 2.05 g/kg/h. Time to maximum plasma concentration and maximal concentration were 12 hours (range, 4 to 24 hours) and 1.30 ng/mL (range, 0.62 to 2.73 ng/mL), respectively. Fentanyl concentrations were maintained at > 0.5 ng/mL for 40 hours after TFP application.
Conclusions and Clinical Relevance—IV administration of fentanyl resulted in a short half-life. Application of a TFP resulted in stable blood fentanyl concentrations in sheep. (Am J Vet Res 2010;71:1127—1132)
