Esophageal pH-monitoring in nonbrachycephalic dogs; a reference.

OBJECTIVE: To establish parameters that describe acidic gastroesophageal reflux (GER) events in nonbrachycephalic, hospitalized dogs without gastrointestinal disease following short total intravenous anesthesia, to establish upper reference limits for parameters that describe GER. STUDY DESIGN: Clinical prospective study. ANIMALS: Healthy, client-owned dogs presenting for elective orthopedic surgery. METHODS: Dogs were sedated with IM methadone (0.2 mg/kg) and medetomidine (5 ug/kg), followed by alfaxalone total intravenous anesthesia. The Digitrapper esophageal dual pH monitoring probe was placed transnasally into the esophagus. Dogs were unsedated during the subsequent recording period. A GER event was defined as esophageal pH less than 4.0. Parameters that described GER were: (1) number of GER events per hour, and (2) cumulative esophageal acid exposure (percentage of recording duration) at each sensor. Upper reference limits were calculated for each parameter. RESULTS: Thirty-five dogs were included (median age 7 years, range 1-12). The median recording duration was 21.1 h (range 13.6-29.3). Productive regurgitation was not noted in any dog. The median number of distal and proximal GER events per hour was 0.3 (range 0-4.3) and 0 (range 0-1), respectively. The median cumulative distal and proximal esophageal acid exposure was 0.2% (range 0.3-9%) and 0% (range 0%-1%), respectively. CONCLUSION: Upper reference limits for distal and proximal GER per hour was 2.4 and 0.4, respectively, and, for cumulative distal and proximal esophageal acid exposure, 2.3% and 0%, respectively. CLINICAL SIGNIFICANCE: Dogs undergoing esophageal pH monitoring in a similar hospital setting with parameters above these upper reference limits have excessive GER.

Tube cystostomy is effective for urinary outflow management in dogs with intervertebral disk extrusion and ischemic myelopathy cranial to the L3 spinal cord segment: 61 dogs (2018-2022).

OBJECTIVE: To describe the application and owner experience of tube cystostomy for management of upper motor neuron urinary bladder dysfunction secondary to intervertebral disk extrusion (IVDE) or ischemic myelopathy, and to report complications associated with cystostomy tube management. ANIMALS: 61 dogs. CLINICAL PRESENTATION: Medical records of dogs with IVDE or ischemic myelopathy cranial to the L3 spinal cord segment that underwent tube cystostomy placement via a short, caudal ventral midline celiotomy were reviewed. Days from tube placement to hospital discharge, days from placement to tube removal, and complications were recorded. An owner questionnaire was distributed to ascertain ease of use and perceived time commitment. RESULTS: 58 dogs were diagnosed with IVDE, and 3 dogs were diagnosed with ischemic myelopathy. The modal neurologic grade at cystostomy tube placement was 4 (range, 3 to 5). The median number of days from cystostomy tube placement to hospital discharge was 1 (range, 0 to 3). Follow-up data was available for 56 dogs. The median number of days from cystostomy tube placement until removal was 19 (range, 3 to 74). Fifteen minor and 6 severe postoperative complications were reported, mainly inadvertent removal (n = 11) and peristomal urine leakage (6). Twenty-seven owners responded to the questionnaire and primarily reported that cystostomy tube use was easy (22/27) and perceived time commitment was low or minimal (20/27). CLINICAL RELEVANCE: Tube cystostomy facilitates early hospital discharge and allows at-home, extended urinary management in dogs recovering from upper motor neuron urinary bladder dysfunction secondary to IVDE or ischemic myelopathy. This technique is simple for owners to use.

Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs.

OBJECTIVES: To document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs. STUDY DESIGN: Experimental, repeated measures, prospective study. ANIMALS: A group of six male adult Greyhound dogs. METHODS: Following general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett's adjustment, p < 0.05. RESULTS: Structural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1-25.9) ng mL-1 NGAL (p = 0.002), 2.54 (1.64-3.43) mg mL-1 CysC (p = 0.009) and 2043 (790-5458) U L-1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein-creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE: Urinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.

Analytical validation and reference intervals for a commercial multiplex assay to measure five novel biomarkers for acute kidney injury in canine urine.

Novel urinary biomarkers are increasingly utilized for the diagnosis of acute kidney injury (AKI) in dogs. Magnetic-bead based immunoassays for the simultaneous measurement of multiple biomarkers represent a potentially efficient and cost effective tool for investigators; however there is limited data to support their reliable use in dogs. Analytical validation of a commercial multiplex assay for the measurement of five AKI biomarkers: clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 and neutrophil gelatinase-associated lipocalin (NGAL) in canine urine was performed. The effect of pre-analytical factors including potential interfering substances and sample storage methods were investigated. Urine from 110 healthy dogs was used to determine reference intervals for each biomarker measured, according to American Society of Veterinary Clinical Pathology guidelines. Additionally, urine from 21 dogs with pyuria was used to evaluate the impact of pyuria on biomarker concentration. The assay performed with acceptable accuracy and precision for the measurement of NGAL only. Clinically relevant urine concentrations of bilirubin, haemoglobin, and synthetic colloid solutions led to interference (mean percentage difference > +/- 15% compared to control) with measurement of all or some of the biomarkers. All biomarkers were stable in urine stored at 20-22 °C for 2 h, 4 °C for 12 h, or -20 °C for 6 months. Reference intervals could not be established for KIM-1 due to unacceptable measurement imprecision (intra- and inter assay coefficient of variation 45% and 20% respectively). Urine NGAL concentration was significantly elevated in pyuria (P < 0.001).

Circumferential esophageal hiatal rim reconstruction for treatment of persistent regurgitation in brachycephalic dogs: 29 cases (2016-2019).

OBJECTIVE: To describe a technique for circumferential esophageal hiatal rim reconstruction and to report outcomes in brachycephalic dogs with persistent regurgitation treated with the technique. ANIMALS: 29 client-owned brachycephalic dogs. PROCEDURES: Dogs that had undergone circumferential esophageal hiatal rim reconstruction between January 1, 2016, and December 31, 2019, for treatment of persistent regurgitation were identified through a search of the medical record database of The Animal Hospital at Murdoch University. Circumferential esophageal hiatal rim reconstruction involved apposition of the medial margins of the left and right pars lumbalis dorsal to the esophagus (reconstructing the dorsal margin) and ventral to the esophagus (reducing the ventral hiatal aperture and completing the circumferential reconstruction). Data collection from the medical records included preoperative, intraoperative, and postoperative (short- and long-term outcomes [≤ 14 days and ≥ 6 months, respectively]) data. RESULTS: In all dogs, substantial laxity of the left and right pars lumbalis and failure of dorsal coaxial alignment were observed, and circumferential esophageal hiatal rim reconstruction and esophagopexy were performed. Results of short-term follow-up indicated reduced regurgitation frequency; however, 7 of 29 dogs continued to have mild regurgitation, which was attributed to esophagitis and resolved with medical management. Long-term follow-up information was available for 19 dogs: regurgitation had resolved in 16 dogs and occurred once weekly in 3 dogs. No ongoing medication was required for any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Circumferential hiatal rim reconstruction combined with esophagopexy substantially reduced regurgitation frequency in dogs of the present study, and we recommend that this procedure be considered for brachycephalic dogs presented with a history of regurgitation unresponsive to medical management.

Comparison of pulmonary function in isoflurane anaesthetized ventilated sheep (Ovis aries) following administration of intravenous xylazine versus medetomidine.

Alpha2 receptor agonists (alpha2-agonists) are useful sedative and analgesic agents in sheep, but have adverse pulmonary effects, which are reportedly similar between different alpha2-agonists. This randomized crossover study compared pulmonary function after intravenous administration of an alpha2-agonist, either xylazine or an equipotent dose of medetomidine in 34 female sheep anaesthetized twice. Pulmonary function was assessed using spirometry, volumetric capnography, arterial blood gas analysis 1 min prior to, and 5 and 10 min after administration of the allocated alpha 2 agonist drug. Pulmonary structural changes were subsequently assessed using computed tomography (CT). Tachypnoea or hypoxaemia prompted reversal with atipamezole and exclusion of data. Data were analysed for a fixed effect of drug using a mixed effect linear model with significance set at p < 0.05. Ten sheep administered xylazine required atipamezole while none of sheep receiving medetomidine did. Xylazine produced significantly higher respiratory frequency, airway pressures, airway resistance and arterial carbon dioxide (CO2), and lower dynamic compliance, tidal volume, CO2 elimination and end tidal CO2 tension and arterial oxygen tension than medetomidine. This was associated with a significantly lower % of aerated tissue and higher % poorly and non-aerated tissue in CT images of sheep receiving xylazine versus medetomidine. In conclusion, xylazine administration produced marked decreases in pulmonary function, in ventilated isoflurane anaesthetized sheep, when compared to an equipotent dose of medetomidine when administered as an intravenous bolus supporting the use of medetomidine when alpha2-agonists are required.

Agreement between invasive blood pressure measured centrally and peripherally in anaesthetized horses.

OBJECTIVE: To determine the agreement of invasive blood pressure measured in the facial, metatarsal and carotid arteries, and evaluate the effects of two haemodynamic conditions on agreement. STUDY DESIGN: Prospective randomized study. ANIMALS: A group of eight horses aged 7 (4-23) years with a body weight of 493 ± 33 kg. METHODS: Horses were anaesthetized and positioned in dorsal recumbency. Invasive blood pressure was measured simultaneously via catheters placed in the facial, metatarsal and carotid arteries. Cardiovascular function and agreement between arteries was assessed before and during administration of phenylephrine and sodium nitroprusside. These were administered until carotid mean pressure (MAPc) increased or decreased from baseline (65 ± 5) to >90 or <50 mmHg, respectively. Data recorded at each sample time included systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures for carotid (c), facial (f) and metatarsal (m) arteries as well as cardiac output (Q˙t) and systemic vascular resistance (SVR). Bland-Altman analysis was used to assess agreement between peripheral and central sites, and regression analysis to determine influence of Q˙t and SVR. RESULTS: The largest difference was observed in SAPc and SAPm with a bias and limits of agreement (LOA) of 2 (-15 to 19) mmHg. The bias (LOA) for MAPc and MAPf was 2 (-4 to 9) mmHg and for MAPc and MAPm was 5 (-4 to 14) mmHg. The best agreement for DAP was seen between DAPc and DAPf with bias (LOA) of 1 (-3 to 5) mmHg. Regression analysis indicated marginal influence on agreement by Q˙t on MAPc and MAPf. CONCLUSIONS AND CLINICAL RELEVANCE: MAP and DAP of the carotid artery were higher than those of the peripheral arteries, which may lead to overzealous treatment of hypotension, albeit maintaining central pressures. Q˙t and SVR did not largely influence the difference between sites.

Agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses under clinical conditions.

OBJECTIVE: To determine agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses undergoing elective surgery. STUDY DESIGN: Prospective balanced incomplete block design. ANIMALS: A total of 18 client-owned horses. METHODS: Invasive blood pressure (IBP) was measured simultaneously in one of the following three combinations: 1) transverse facial and facial artery; 2) transverse facial and metatarsal artery; and 3) facial and metatarsal artery. The agreement in blood pressure measured for each combination was performed in six horses. At each sample time, systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were measured concurrently in each artery, and the mean of three consecutive measurements was recorded. The position of horse, heart rate and use of dobutamine were also recorded. Bland-Altman analysis was used to assess agreement between sites. RESULTS: A total of 54 paired measurements were obtained, with 18 paired measurements from each combination. All paired measurements showed poor and haphazard (nonsystematic) agreement. The widest limit of agreement was 51 mmHg for SAP measured in the facial artery and metatarsal artery, with a bias of -11 mmHg. The smallest limit of agreement was 16 mmHg for MAP measured in the transverse facial and metatarsal artery, with a bias of 1 mmHg. CONCLUSIONS AND CLINICAL RELEVANCE: There was poor and haphazard agreement for SAP, MAP and DAP measured in each pair of peripheral arteries in this study. These results show that blood pressure measured in different peripheral arteries cannot be used interchangeably. This has implications for studies that use IBP as an outcome variable and studies determining agreement between noninvasive blood pressure and IBP measurements in horses under general anaesthesia.

The Effect of Tibial Plateau Levelling Osteotomy on Stifle Extensor Mechanism Load: A Canine Ex Vivo Study.

OBJECTIVE: To evaluate the effect of tibial plateau levelling osteotomy on stifle extensor mechanism load in an ex vivo cruciate-intact canine cadaveric model. STUDY DESIGN: Ex vivo mechanical testing study. ANIMALS: Cadaveric canine pelvic limbs (n = 6). MATERIALS AND METHODS: A 21-mm tibial radial osteotomy was performed on pelvic limbs (n = 6) prior to being mounted into a load-bearing limb press. The proximal tibial segment was incrementally rotated until the anatomical tibial plateau angle had been rotated to at least 1°. The proportional change in stifle extensor mechanism load between the anatomical tibial plateau angle and the neutralized (∼6.5 degrees) and over-rotated (∼1°) tibial plateau angle was analysed using a one-sample t-test against a null hypothesis of no change. A p-value ≤0.05 was considered significant. RESULTS: There was no significant change in the stifle extensor mechanism load from the anatomical tibial plateau angle (308 N [261-355 N]) to the neutralized tibial plateau angle (313 N [254-372 N]; p =.81), or from the anatomical tibial plateau angle to the over-rotated tibial plateau angle (303 N [254-352 N; p = 0.67). CONCLUSION: Tibial plateau levelling osteotomy does not significantly alter stifle extensor mechanism load at either a neutralized or over-rotated tibial plateau angle in our cruciate-intact model.

Paradoxical bradycardia during surgical caudal vena cava occlusion in an anesthetized dog.

OBJECTIVE: To describe the anesthetic management of a dog undergoing caudal vena cava (CVC) occlusion during adrenalectomy, and to discuss a reflex bradycardia that was observed during the procedure. CASE SUMMARY: General anesthesia of a 10-year-old Rhodesian ridgeback for excision of an adrenal mass and associated CVC tumor thrombus was performed. The dog was premedicated with IV methadone and anesthesia was induced with IV alfaxalone and maintained with isoflurane in 100% oxygen. An IV remifentanil infusion was administered for intraoperative analgesia. Surgical removal of the thrombus necessitated temporary complete occlusion of the CVC. During CVC occlusion an acute paradoxical bradycardia occurred, which was successfully treated with IV atropine. The cardiovascular change resembled a Bezold-Jarisch or reverse Bainbridge reflex, and was believed to be mediated by cardiac mechanoreceptors following the sudden decrease in preload. Increased myocardial contractility subsequent to increased sympathetic nervous system activity may also have contributed. A decrease in urine output was observed following CVC occlusion but had returned to normal 2 hours following the end of anesthesia. Recovery from anesthesia was otherwise uneventful. NEW OR UNIQUE INFORMATION PROVIDED: Although the mechanism is unclear, a paradoxical bradycardia may occur during complete CVC occlusion in the dog. Factors that increase sympathetic nervous system outflow, such as administration of dopamine, may have contributed to the occurrence of the reflex.

The effect of intramedullary pin size and plate working length on plate strain in locking compression plate-rod constructs under axial load.

OBJECTIVE: To investigate the effect of intramedullary pin size and plate working length on plate strain in locking compression plate-rod constructs. METHODS: A synthetic bone model with a 40 mm fracture gap was used. Locking compression plates with monocortical locking screws were tested with no pin (LCP-Mono) and intramedullary pins of 20% (LCPR-20), 30% (LCPR-30) and 40% (LCPR-40) of intramedullary diameter. Two screws per fragment modelled a long (8-hole) and short (4-hole) plate working length. Strain responses to axial compression were recorded at six regions of the plate via three-dimensional digital image correlation. RESULTS: The addition of a pin of any size provided a significant decrease in plate strain. For the long working length, LCPR-30 and LCPR-40 had significantly lower strain than the LCPR-20, and plate strain was significantly higher adjacent to the screw closest to the fracture site. For the short working length, there was no significant difference in strain across any LCPR constructs or at any region of the plate. Plate strain was significantly lower for the short working length compared to the long working length for the LCP-Mono and LCPR-20 constructs, but not for the LCPR-30 and LCPR-40 constructs. CLINICAL SIGNIFICANCE: The increase in plate strain encountered with a long working length can be overcome by the use of a pin of 30-40% intramedullary diameter. Where placement of a large diameter pin is not possible, screws should be placed as close to the fracture gap as possible to minimize plate strain and distribute it more evenly over the plate.

Platelet function and activation in Cavalier King Charles Spaniels with subclinical chronic valvular heart disease.

OBJECTIVE To assess platelet closure time (CT), mean platelet component (MPC) concentration, and platelet component distribution width (PCDW) in dogs with subclinical chronic valvular heart disease. ANIMALS 89 Cavalier King Charles Spaniels (CKCSs) and 39 control dogs (not CKCSs). PROCEDURES Platelet count, MPC concentration, PCDW, and Hct were measured by use of a hematology analyzer, and CT was measured by use of a platelet function analyzer. Murmur grade and echocardiographic variables (mitral valve regurgitant jet size relative to left atrial area, left atrial-to-aortic diameter ratio, and left ventricular internal dimensions) were recorded. Associations between explanatory variables (sex, age, murmur grade, echocardiographic variables, platelet count, and Hct) and outcomes (CT, MPC concentration, and PCDW) were examined by use of multivariate regression models. RESULTS A model with 5 variables best explained variation in CT (R(2), 0.74), with > 60% of the variance of CT explained by mitral valve regurgitant jet size. The model of best fit to explain variation in MPC concentration included only platelet count (R(2), 0.24). The model of best fit to explain variation in PCDW included platelet count and sex (R(2), 0.25). CONCLUSIONS AND CLINICAL RELEVANCE In this study, a significant effect of mitral valve regurgitant jet size on CT was consistent with platelet dysfunction. However, platelet activation, as assessed on the basis of the MPC concentration and PCDW, was not a feature of subclinical chronic valvular heart disease in CKCSs.

Urinary neutrophil gelatinase-associated lipocalin concentration changes after acute haemorrhage and colloid-mediated reperfusion in anaesthetized dogs.

OBJECTIVE: To determine changes in urine neutrophil gelatinase-associated lipocalin concentration (uNGAL) in anaesthetized Greyhound dogs that developed acute tubular damage following haemorrhage and resuscitation with colloid-based fluids. STUDY DESIGN: Prospective experimental study. ANIMALS: Seven healthy adult entire male Greyhound dogs. METHODS: During isoflurane anaesthesia, approximately 50 mL kg(-1) of blood was removed to maintain mean arterial pressure (MAP) ≤40 mmHg for 1 hour followed by gelatin-based colloid administration to maintain MAP ≥60 mmHg for 3 hours. Data, including oxygen extraction ratio and uNGAL, were collected before (T0) and immediately following (T1) haemorrhage, and hourly during reperfusion (T2-T4). After T4, dogs were euthanized and renal tissue was collected for histology. Statistical analysis was performed using repeated-measures one-way anova. Data are presented as means (95% confidence interval). RESULTS: Histology identified renal tubular epithelial damage in all dogs. Urine NGAL concentration increased from 12.1 (0-30.6) ng mL(-1) at T0 to 122.0 (64.1-180.0) ng mL(-1) by T3. Compared with T0, uNGAL was significantly higher at T3 (p = 0.016) and was increased 24-fold. CONCLUSIONS AND CLINICAL RELEVANCE: Despite wide individual variation in baseline uNGAL, increases in uNGAL were observed in all dogs, suggesting that this biomarker has the potential to detect renal tubular injury following haemorrhage-induced hypotension and colloid-mediated reperfusion.

Biomechanical comparison of a locking compression plate combined with an intramedullary pin or a polyetheretherketone rod in a cadaveric canine tibia gap model.

OBJECTIVE: To compare the biomechanical properties of a 10-hole 3.5 mm locking compression plate (LCP) with 2 proximal and 2 distal bicortical locked screws reinforced with either a Steinmann pin of 30-40% the medullary diameter or a poly-ether-ether-ketone (PEEK) rod of ∼75% the medullary diameter in a cadaveric tibia gap model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Cadaveric canine tibias (n = 8 pair). METHODS: Each construct had a 10-hole 3.5 mm LCP with 2 screws per fracture fragment using a comminuted tibia gap model. The Steinmann pin constructs had a 2.4 mm intramedullary pin whereas the PEEK-rod constructs had a 6 mm intramedullary PEEK rod placed. Biomechanical testing included non-destructive bi-planar 4 point bending, torsion testing, and destructive axial compression. Testing produced the responses of failure load (N) in axial compression, stiffness (N/mm or N/°) in axial compression, torsion, lateral-medial, and caudal-cranial 4 point bending. Screw position within the PEEK-rods was determined after explantation. RESULTS: The PEEK-rod constructs were significantly stiffer in axial compression (P < .005), lateral-medial 4 point bending (P < .001), and in torsional loading (P < .031) than the Steinman pin constructs. There was no significant difference between the constructs for stiffness in caudal-cranial 4 point bending (P = .32). The PEEK-rod constructs failed at a significantly higher load than the Steinmann pin constructs (P < .001). All constructs failed by yielding through plastic deformation. Each screw penetrated the PEEK rod in all constructs but the position of the screw varied. CONCLUSION: PEEK-rod constructs failed at significantly higher loads and were significantly stiffer in 4 point lateral-medial bending, axial compression, and torsion when compared with Steinmann pin constructs.

Effect of hydroxyethyl starch 130/0.4 and 200/0.5 solutions on canine platelet function in vitro.

OBJECTIVE: To determine whether dilution of blood samples from healthy dogs with 2 hydroxyethyl starch (HES) solutions, HES 130/0.4 and HES 200/0.5, would result in platelet dysfunction as measured by closure time (Ct) beyond a dilutional effect. SAMPLE: Citrated blood samples from 10 healthy dogs with a Ct within reference limits (52 to 86 seconds). PROCEDURES: Blood samples were diluted 1:9 and 1:3 with 6% HES 130/0.4 and 10% HES 200/0.5 solutions and saline (0.9% NaCl) solution. Dilutions at 1:9 and 1:3 mimicked 10 mL/kg and 30 mL/kg doses, respectively, ignoring in vivo redistribution. Closure time was measured with a platelet function analyzer and compared among dilutions. RESULTS: A dilutional effect on Ct was evident for the 1:3 dilution, compared with the 1:9 dilution, but only HES 200/0.5 increased the Ct beyond the dilutional effect at the 1:3 dilution, to a median Ct of 125 seconds (interquartile range, 117.5 to 139.5 seconds). No effect of HES or dilution on Ct was identified at the 1:9 dilution. CONCLUSIONS AND CLINICAL RELEVANCE: 1:3 dilution of blood samples from healthy dogs with HES 200/0.5 but not HES 130/0.4 significantly increased Ct beyond the dilutional effect, suggesting that IV administration of HES 200/0.5 in dogs might cause platelet dysfunction.

Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.

OBJECTIVE: To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. RESULTS: In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. CONCLUSIONS AND CLINICAL RELEVANCE: Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.

Glucose detection and concentration estimation in feline urine samples with the Bayer Multistix and Purina Glucotest.

The Bayer Multistix are commonly used for detection and estimation of feline glucosuria by veterinarians and cat owners. A newer product, the Purina Glucotest, utilizes the same enzymatic technology for detection of glucose, but has been designed for home use as a litter additive that allows interpretation of glucosuria over an 8-h period. The objectives of this study were to assess the sensitivity, specificity, and accuracy of the Glucotest and Multistix, and to assess the 8-h color stability of the Glucotest. Overall, the Glucotest had greater sensitivity and specificity than the Multistix, and more accurately estimated urine glucose concentration if evaluated at least 30 min after exposure to urine. A significant lack of agreement between the results obtained immediately after exposure to urine vs after 30 min and 8 h contradicts the 8-h color stability claim, but the change in urine glucose concentration estimation over time resulted in improved test accuracy at the 30 and 480 min time points.

In vitro effect of carprofen and meloxicam on the conductance and permeability to mannitol and the histologic appearance of the gastric mucosa of dogs.

OBJECTIVE: To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa. SAMPLE: Gastric mucosa from 6 mature mixed-breed dogs. PROCEDURES: Sections of gastric mucosa were mounted in Ussing chambers, and carprofen (40 or 400µg/mL [CAR40 and CAR400, respectively]), meloxicam (8 or 80µg/mL [MEL8 and MEL80, respectively]), or no drug (controls) was added to the bathing solution. For all sections, conductance was calculated every 15 minutes for 240 minutes and flux of mannitol was calculated for 3 consecutive 1-hour periods; histologic examination was performed after the experiment. The area under the conductance-time curve for each chamber was calculated. Values of conductance × time, flux of mannitol, and the frequency distribution of histologic findings were analyzed for treatment effects. RESULTS: For CAR400- and MEL80-treated sections, conductance X time was significantly higher than that for control and MEL8-treated sections. The effect of CAR40 treatment was not different from that of any other treatment. Over the three 1-hour periods, mannitol flux increased significantly in MEL80-, CAR40-, and CAR400-treated sections but not in MEL8- treated or control sections. Major histologic changes including epithelial cell sloughing were limited to the CAR400-treated sections. CONCLUSIONS AND CLINICAL RELEVANCE: In the gastric mucosa of dogs, carprofen and meloxicam increased in vitro conductance and permeability to mannitol. At a concentration of 400 µg/mL, carprofen caused sloughing of epithelial cells. Carprofen and meloxicam appear to compromise gastric mucosal integrity and barrier function in dogs.

Assessment of the relationship between body weight and gastrointestinal transit times measured by use of a wireless motility capsule system in dogs.

OBJECTIVE: To assess the relationship between body weight and gastrointestinal transit times measured by use of a wireless motility capsule (WMC) system in healthy dogs. ANIMALS: 31 healthy adult dogs that weighed between 19.6 and 81.2 kg. PROCEDURES: Food was withheld overnight. The following morning, a WMC was orally administered to each dog, and each dog was then fed a test meal that provided a fourth of the daily energy requirements. A vest was fitted on each dog to hold a receiver that collected and stored data from the WMC. Measurements were obtained with each dog in its home environment. Regression analysis was used to assess the relationship between body weight and gastrointestinal transit times. RESULTS: Gastric emptying time (GET) ranged from 405 to 897 minutes, small bowel transit time (SBTT) ranged from 96 to 224 minutes, large bowel transit time (LBTT) ranged from 427 to 2,573 minutes, and total transit time (TTT) ranged from 1,294 to 3,443 minutes. There was no positive relationship between body weight and gastrointestinal transit times. A nonlinear inverse relationship between body weight and GET and between body weight and SBTT best fit the data. The LBTT could not be explained by this model and likely influenced the poor fit for the TTT. CONCLUSIONS AND CLINICAL RELEVANCE: A positive relationship did not exist between body weight and gastrointestinal transit times. Dogs with the lowest body weight of the cohort appeared to have longer gastric and small intestinal transit times than did large- and giant-breed dogs.

Variability associated with repeated measurements of gastrointestinal tract motility in dogs obtained by use of a wireless motility capsule system and scintigraphy.

OBJECTIVE: To compare repeatability of measurements of gastrointestinal tract motility in healthy dogs obtained by use of a wireless motility capsule (WMC) and scintigraphy. ANIMALS: 6 healthy adult dogs (mean +/- SD body weight, 21.5 +/- 1.8 kg). PROCEDURES: A radiolabeled test meal was offered immediately after oral administration of a WMC. Serial static scintigraphic abdominal images were acquired for 270 minutes. A dedicated remote receiver was used for data collection from the WMC until the WMC was expelled in the feces. Each dog was evaluated 3 times at intervals of 1 to 2 weeks. RESULTS: Mean gastric emptying half-time measured by use of scintigraphy (T(1/2)-GES) for each dog ranged from 99.9 to 181.2 minutes. Mean gastric emptying time (GET) measured by use of the WMC (GET-WMC) in each dog ranged from 385.3 to 669.7 minutes. Mean coefficient of variation was 11.8% for T(1/2)-GES and 7.8% for GET-WMC. The intraclass correlation coefficient was 69% for T(1/2)-GES and 71% for GET-WMC. Results for a nested analysis of covariance suggested that both methods were comparable for the evaluation of gastric emptying. CONCLUSIONS AND CLINICAL RELEVANCE: Scintigraphy and a WMC system had similar variation for assessment of gastric emptying. Moderate intraindividual variability was detected for both methods and must be considered when interpreting test results for individual dogs. Repeatability of measurements obtained by use of the WMC was equivalent to that obtained by use of scintigraphy. The WMC system offers a nonradioactive, user-friendly method for assessment of gastric emptying in dogs.