OBJECTIVE To measure changes in interleukin-8 (IL-8), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) concentrations in stored canine packed RBCs (PRBCs) over time and assess the effect of leukoreduction on these cytokine concentrations.
ANIMALS 12 anesthetized healthy Greyhounds.
PROCEDURES 1 unit of whole blood from each dog was processed into PRBCs. Half of each PRBCs unit was passed through a leukoreduction filter to produce a leukoreduced unit, and the remaining blood was kept as a nonleukoreduced unit. All units had a CBC performed on day 0 (day of collection) and were stored at 2° to 6°C. Samples were collected from leukoreduced and nonleukoreduced units on days 0, 10, 20, 30, and 37 and centrifuged; the supernatant was stored at −80°C until analysis. Canine TNF-α and IL-8 concentrations were assessed with a multiplexed genomic and proteomic biomarker analyzer, and canine IL-1β concentration was measured by ELISA.
RESULTS Leukocyte counts were decreased by ≥ 99.9% in all leukoreduced units. Median TNF-α and IL-1β concentrations were not significantly different between leukoreduced and nonleukoreduced units and did not change significantly during storage; median IL-8 concentration was significantly higher in nonleukoreduced versus leukoreduced units on all days, and was greater at all time points after ≥ 10 days of storage than on day 0. Median IL-8 concentration in leukoreduced units did not increase during storage.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that leukoreduction was effective for the removal of leukocytes from canine PRBCs and prevented significant increases in IL-8 concentration during storage. Further studies are needed to evaluate whether leukoreduction reduces cytokine-associated complications of transfusion.
To describe a technique for circumferential esophageal hiatal rim reconstruction and to report outcomes in brachycephalic dogs with persistent regurgitation treated with the technique.
29 client-owned brachycephalic dogs.
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.
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.
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.
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.
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).
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.
Objective—To evaluate the radial growth assay for use in in vitro susceptibility testing of Pythium insidiosum and a Lagenidium sp and to assess susceptibility of representative isolates to itraconazole, posaconazole, voriconazole, terbinafine, caspofungin, and mefenoxam.
Sample Population—6 isolates each of P insidiosum and Lagenidium sp.
Procedures—Isolates were plated in triplicate onto agar supplemented with antifungal compounds at concentrations of 0.025 to 8 μg/mL. Isolates on dimethyl sulfoxide– and water-supplemented agar served as control samples. Effect of antifungal concentration on colony diameter was assessed with a mixed linear model. Assay variability was assessed with the coefficient of variation.
Results—Colony growth was uniform (mean intra-assay and interassay coefficients of variation were < 5%). Minimal inhibition was evident with voriconazole and posaconazole at 8 μg/mL. Terbinafine at 8 μg/mL significantly reduced growth of P insidiosum and at ≥ 1 μg/mL significantly reduced growth of the Lagenidium sp. Caspofungin and mefenoxam (concentrations ≥ 1 μg/mL and ≥ 0.025 μg/mL, respectively) significantly reduced growth of both pathogens. Mefenoxam at 0.1 μg/mL caused > 50% growth inhibition in 11 of 12 isolates and at 1 μg/mL caused > 90% inhibition in all isolates.
Conclusions and Clinical Relevance—Results suggested that the radial growth assay was a simple, reproducible technique for susceptibility testing of P insidiosum and a Lagenidium sp. Azoles had limited activity, whereas terbinafine and caspofungin caused significant but minimal to moderate inhibition. Only mefenoxam had a profound effect on both pathogens at concentrations likely to be achievable in tissues.
Objective—To evaluate the effect of treadmill incline on muscle activity and joint range of motion (ROM) in hind limbs of dogs.
Animals—8 purpose-bred healthy adult hounds.
Procedures—Activities of the hamstring (semimembranosus, semitendinosus, and biceps femoris muscles), gluteal (superficial, middle, and deep gluteal muscles), and quadriceps (femoris, vastus lateralis, vastus intermedius, and vastus medialis muscles) muscle groups and hip and stifle joint ROM were measured with surface electrogoniometric and myographic sensors in hounds walking on a treadmill at 0.54 m/s at inclines of 5%, 0%, and −5% in random order. Mean electromyographic activities and mean ROMs at each inclination were compared for swing and stance phases.
Results—Treadmill inclination did not affect duration of the stance and swing phases or the whole stride. When treadmill inclination was increased from −5% to 5%, hip joint ROM increased and the degree of stifle joint extension decreased significantly. In the beginning of the stance phase, activity of the hamstring muscle group was significantly increased when walking at a 5% incline versus a 5% decline. In the end of the stance phase, that activity was significantly increased when walking at a 5% incline versus at a 5% decline or on a flat surface. Activity of the gluteal and quadriceps muscle groups was not affected when treadmill inclination changed.
Conclusions and Clinical Relevance—Treadmill inclination affected joint kinematics only slightly. Walking on a treadmill at a 5% incline had more potential to strengthen the hamstring muscle group than walking on a treadmill with a flat or declined surface.
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.
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.
Objective—To characterize the in vitro effects of
oxytocin, acepromazine, xylazine, butorphanol,
detomidine, dantrolene, isoproterenol, and terbutaline
on skeletal and smooth muscle from the
Animals—14 adult horses without digestive tract disease.
Procedure—Circular and longitudinal strips from
the skeletal and smooth muscle of the esophagus
were suspended in tissue baths, connected to
force-displacement transducers interfaced with a
physiograph, and electrical field stimulation was
applied. Cumulative concentration-response curves
were generated for oxytocin, acepromazine,
xylazine, detomidine, butorphanol, isoproterenol,
terbutaline, and dantrolene. Mean maximum twitch
amplitude for 3 contractions/min was recorded and
compared with predrug-vehicle values for the
skeletal muscle segments, and area under the
curve (AUC) for 3 contractions/min was compared
with predrug-vehicle values for the smooth muscle
Results—No drugs caused a significant change in
skeletal muscle response. In smooth muscle, isoproterenol,
terbutaline, and oxytocin significantly
reduced AUC in a concentration-dependent manner.
Maximum reduction in AUC was 69% at 10–4M for
isoproterenol, 63% at 10–5M for terbutaline, and
64% at 10–4M for oxytocin.
Conclusions and Clinical Relevance—Isoproterenol,
terbutaline, and oxytocin cause relaxation of the
smooth muscle portion of the esophagus. The clinical
relaxant effects on the proximal portion of the esophagus
reported of drugs such as oxytocin, detomidine,
and acepromazine may be the result of centrally mediated
mechanisms. (Am J Vet Res 2002;63:1732–1737)
Objective—To compare effects of oxytocin, acepromazine
maleate, xylazine hydrochloride-butorphanol
tartrate, guaifenesin, and detomidine hydrochloride
on esophageal manometric pressure in horses.
Animals—8 healthy adult horses.
Procedure—A nasogastric tube, modified with 3
polyethylene tubes that exited at the postpharyngeal
area, thoracic inlet, and distal portion of the
esophagus, was fitted for each horse. Amplitude,
duration, and rate of propagation of pressure waveforms
induced by swallows were measured at 5, 10,
20, 30, and 40 minutes after administration of oxytocin,
detomidine, acepromazine, xylazine-butorphanol,
guaifenesin, or saline (0.9% NaCl) solution.
Number of spontaneous swallows, spontaneous
events (contractions that occurred in the absence of
a swallow stimulus), and high-pressure events (sustained
increases in baseline pressure of > 10 mm
Hg) were compared before and after drug administration.
Results—At 5 minutes after administration, detomidine
increased waveform amplitude and decreased
waveform duration at the thoracic inlet. At 10 minutes
after administration, detomidine increased waveform
duration at the thoracic inlet. Acepromazine administration
increased the number of spontaneous events
at the thoracic inlet and distal portion of the esophagus.
Acepromazine and detomidine administration
increased the number of high-pressure events at the
thoracic inlet. Guaifenesin administration increased
the number of spontaneous events at the thoracic
inlet. Xylazine-butorphanol, detomidine, acepromazine,
and guaifenesin administration decreased the
number of spontaneous swallows.
Conclusions and Clinical Relevance—Detomidine,
acepromazine, and a combination of xylazine butorphanol
had the greatest effect on esophageal motility
when evaluated manometrically. Reduction in spontaneous
swallowing and changes in normal, coordinated
peristaltic activity are the most clinically relevant
effects. (Am J Vet Res 2002;63:1738–1744)
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.