Objective-To determine plasma disposition after dermal application of a liposome-encapsulated formulation of lidocaine in cats. Animals-6 healthy adult cats with a mean (+/- SD) body weight of 4.1 +/- 0.44 kg. Procedure-CBC determination and biochemical analysis of blood samples were performed for all cats. Cats were anesthetized by use of isoflurane, and catheters were placed IV in a central vein. The next day, blood samples were obtained from the catheters before and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after applying a 4% liposome-encapsulated lidocaine cream (15 mg/kg) to a clipped area over the cephalic vein. Plasma concentrations of lidocaine were analyzed with a high-performance liquid chromatography assay. Results-Two cats had minimal transdermal absorption of lidocaine, with lidocaine concentrations below the sensitivity of the assay at all but 1 or 2 time points. In the other 4 cats, the median maximum plasma concentration was 149.5 ng/ml, the median time to maximum plasma concentration was 2 hours, and the median area under the concentration versus time curve from zero to infinity was 1014.5 ng·h/ml. Conclusions and Clinical Relevance-Maximum plasma concentrations of lidocaine remained substantially below toxic plasma concentrations for cats. On the basis of these data, topical administration of a liposome-encapsulated lidocaine formulation at a dose of 15 mg/kg appears to be safe for use in healthy adult cats.

Objective-To determine cutaneous analgesia, hemodynamic and respiratory effects, and β-endorphin concentration in spinal fluid and plasma of horses after acupuncture and electroacupuncture (EA). Animals-8 healthy 10- to 20-year-old mares that weighed between 470 and 600 kg. Procedure-Each horse received 2 hours of acupuncture and 2 hours of PAES at acupoints Bladder 18, 23, 25, and 28 on both sides of the vertebral column as well as sham needle placement (control treatment). Each treatment was administered in a random order. At least 7 days elapsed between treatments. Nociceptive cutaneous pain threshold was measured by use of skin twitch reflex latency (STRL) and avoidance to radiant heat (≤ 50°C) in the lumbar area. Skin temperature, cardiovascular and respiratory variables, and β-endorphin concentration in spinal fluid (CSF-EN) and plasma (plasma-EN) were measured. Results-Acupuncture and EA significantly increased STRL and skin temperature. The CSF-EN was significantly increased from baseline values 30 to 120 minutes after onset of EA, but it did not change after acupuncture and control treatments. Heart and respiratory rates, rectal temperature, arterial blood pressure, Hct, total solids and bicarbonate concentrations, base excess, plasma-EN, and results of blood gas analyses were not significantly different from baseline values after acupuncture, EA, and control treatments. Conclusion and Clinical Relevance-Administration of EA was more effective than acupuncture for activating the spinal cord to release beta-endorphins into the CSF of horses. Acupuncture and PAES provided cutaneous analgesia in horses without adverse cardiovascular and respiratory effects.

Objective-To determine whether intrathecal (IT) or IV administration of oxytocin will diminish amplitude of the reflex-evoked muscle action potential (REMP) in the digastricus muscle during electrical stimulation of the tooth pulp in anesthetized dogs, thus suggesting an analgesic effect for oxytocin. Animals-6 male Beagles that were 2 to 6 years old. Procedure-Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin by both the IT and IV routes of administration. Noninvasive dental dolorimetry was used to assess changes in pain threshold following administration of treatments. Effectiveness of analgesia was determined on the basis of change in REMP amplitude in the digastricus muscle. Results-Morphine administered IV significantly inhibited REMP amplitude, compared with IV administration of saline solution or oxytocin. There was not a significant change in REMP amplitude between saline solution and oxytocin administered IV. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution or oxytocin. Intrathecal administration of oxytocin significantly increased REMP amplitude, compared with IT administration of saline solution or morphine. Conclusions and Clinical Relevance-Although IV administration of oxytocin did not have an effect on REMP amplitude, compared with IV administration of saline solution, IT administration of oxytocin had the opposite effect of morphine and increased REMP amplitude of the digastricus muscle. These data do not support the use of oxytocin as an analgesic agent in dogs.

Objective-To determine whether the hyoepiglotticus muscle has respiratory-related electromyographic activity and whether electrical stimulation of this muscle changes the position and conformation of the epiglottis, thereby altering dimensions of the aditus laryngis. Animals-6 Standardbred horses. Procedure-Horses were anesthetized, and a bipolar fine-wire electrode was placed in the hyoepiglotticus muscle of each horse. Endoscopic images of the nasopharynx and larynx were recorded during electrical stimulation of the hyoepiglotticus muscle in standing, unsedated horses. Dorsoventral length and area of the aditus laryngis were measured on images obtained before and during electrical stimulation. Electromyographic activity of the hyoepiglotticus muscle and nasopharyngeal pressures were measured while horses exercised on a treadmill at 50, 75, 90, and 100% of the speed that produced maximum heart rate. Results-Electrical stimulation of the hyoepiglotticus muscle changed the shape of the epiglottis, displaced it ventrally, and significantly increased the dorsoventral length and area of the aditus laryngis. The hyoepiglotticus muscle had inspiratory activity that increased significantly with treadmill speed as a result of an increase in phasic and tonic activity. Expiratory activity of the hyoepiglotticus muscle did not change with treadmill speed in 4 of 6 horses. Conclusions and Clinical Relevance-Findings reported here suggest that contraction of the hyoepiglotticus muscle increases dimensions of the airway in horses by depressing the epiglottis ventrally during intense breathing efforts. The hyoepiglotticus muscle may be an important muscle for dilating the airway in horses, and contraction of the hyoepiglotticus muscle may induce conformational changes in the epiglottis.

Objective-To evaluate dose-sparing effects of medetomidine-midazolam (MM), acepromazinebutorphanol (AB), and midazolam-butorphanol (MB) on the induction dose of thiopental and propofol and to examine cardiopulmonary changes in dogs. Animals-23 healthy Beagles. Procedure-Dogs were administered MM, AB, MB, or physiologic saline (0.9% NaCl) solution (PS) IM, and anesthesia was induced with thiopental or propofol. Cardiopulmonary measurements were obtained before and after administration of medication and 0, 5, 10, and 15 minutes after endotracheal intubation. Results-Induction doses were reduced significantly by preanesthetic administration of MM, AB, and MB (thiopental, 20, 45, and 46% after administration of PS; propofol, 42, 58, and 74% after administration of PS, respectively). Recovery time in dogs administered MM-thiopental or MM-propofol and AB-propofol were significantly prolonged, compared with recovery time in dogs administered PS-thiopental or PS-propofol. Relatively large cardiovascular changes were induced by administration of MM, which were sustained even after the induction of anesthesia. Administration of AB and MB induced cardiovascular changes during and immediately after endotracheal intubation that were significantly decreased by induction with thiopental or propofol. However, mild hypotension developed with AB-propofol. Apnea was observed in dogs administered MM during induction of anesthesia, but most respiratory variables did not change significantly. Conclusions and Clinical Relevance-Preanesthetic medication with MM greatly reduced the anesthesia induction dose of thiopental and propofol but caused noticeable cardiopulmonary changes. Preanesthetic medication with AB and MB moderately reduced the induction dose of thiopental and propofol and ameliorated cardiovascular changes induced by these anesthetics, although AB caused mild hypotension.

Objective-To determine whether alterations in myoplasmic calcium regulation can be identified in muscle cell cultures (myotubes) and intact muscle fiber bundles derived from Thoroughbreds affected with recurrent exertional rhabdomyolysis (RER). Animals-6 related Thoroughbreds with RER and 8 clinically normal (control) Thoroughbred or crossbred horses. Procedures-Myotube cell cultures were grown from satellite cells obtained from muscle biopsy specimens of RER-affected and control horses. Fura-2 fluorescence was used to measure resting myoplasmic calcium concentration as well as caffeine- and 4-chloro-m-cresol (4-CMC)-induced increases in myoplasmic calcium. In addition, intact intercostal muscle fiber bundles were prepared from both types of horses, and their sensitivities to caffeine- and 4-CMC-induced contractures were determined. Results-Myotubes of RER-affected and control horses had identical resting myoplasmic calcium concentrations. Myotubes from RER-affected horses had significantly higher myoplasmic calcium concentrations than myotubes from control horses following the addition of ≥ 2mM caffeine; however, there was no difference in their response to 4-CMC (greater than 1mM). Caffeine contracture thresholds for RER and control intact muscle cell bundles (2 vs 10mM, respectively) were significantly different, but 4-CMC contracture thresholds of muscle bundles from RER-affected and control horses (500µM) did not differ. Conclusions and Clinical Relevance-An increase in caffeine sensitivity of muscle cells derived from a family of related RER-affected horses was detected in vitro by use of cell culture with calcium imaging and by use of fiber bundle contractility techniques. An alteration in muscle cell calcium regulation is a primary factor in the cause of this heritable myopathy.

Objective-To determine the effect of glucocorticoids on the induction of alkaline phosphatase (ALP) isoenzymes in the liver, kidneys, and intestinal mucosa, 3 tissues that are principally responsible for ALP synthesis in dogs. Sample Population-Tissues from the liver, kidneys, and intestinal mucosa of 6 dogs treated with 1 mg of prednisone/kg/d for 32 days and 6 untreated control dogs. Procedure-Using canine-specific primers for the ALP isoenzymes, a reverse transcription-polymerase chain reaction assay was designed to measure liver ALP (LALP) and intestinal ALP (IALP) mRNA and heterogeneous nuclear RNA (hnRNA) expression in tissues from the liver and kidneys and intestinal mucosa of glucocorticoid-treated and control dogs. Tissue ALP isoenzyme activities were compared between the groups. Results-The LALP activity and mRNA concentrations increased in tissues of the liver and kidneys in dogs treated with prednisone, whereas LALP hnRNA increased only in liver tissues. The IALP activity and mRNA expression increased in intestinal mucosa and liver tissues in prednisone-treated dogs. We did not detect an increase in IALP hnRNA expression in these tissues. Conclusions and Clinical Relevance-Synthesis of ALP is increased in the liver, kidneys, and intestinal mucosa of dogs in response to prednisone treatment. This response appears to be regulated at the transcriptional level, but mechanisms may differ between LALP and IALP.

Objective-To determine the effects of recombinant equine interleukin -1beta (reIL-1beta) and 4 anti-inflammatory compounds on the expression and activity of cyclooxygenase (COX)-2 in cultured equine chondrocytes. Sample Population-Articular cartilage from 9 young adult horses. Procedure-Reverse transcriptase-polymerase chain reaction methods were used to amplify a portion of equine COX-2 to prepare a cDNA probe. Northern blot analysis was used to quantify the expression of COX-2 in first-passage cultures of equine articular chondrocytes propagated in media containing dexamethasone (DEX), phenylbutazone (PBZ), polysulfated glycosaminoglycan, and hyaluronan, each at concentrations of 10 and 100 micrograms/ml and each with or without reIL-1beta. A commercial immunoassay was used to determine prostaglandin E2 (PGE2) concentrations in conditioned medium of similarly treated cells to quantify COX-2 activity. Results-Addition of reIL-1beta increased the expression of COX-2 in a dose-dependent manner, which was paralleled by an increased concentration of PGE2 in culture medium. Concentration of PGE2 in spent medium from reIL-1beta-treated chondrocytes was significantly reduced by DEX and PBZ; however, only DEX significantly reduced gene expression of COX-2. Conclusions and Clinical Relevance-Prostaglandin E2 is considered to be an important mediator in the pathophysiologic processes of arthritis, and cultured chondrocytes respond to interleukin-1 with enhanced expression and activity of COX-2. Palliative relief in affected horses is probably attributable, in part, to inhibition of PGE2 synthesis; however, analysis of these data suggests that of the 4 compounds tested, only DEX affects pretranslational regulation of the COX-2 gene in cultured equine chondrocytes.

Objective-To determine localization of tartrate-resistant acid phosphatase (TRAP) and cathepsin K in ruptured and healthy cranial cruciate ligaments (CCL) in dogs. Animals-30 dogs with ruptured CCL, 8 aged dogs without ruptured CCL, and 9 young dogs without ruptured CCL. Procedure-The CCL was examined histologically and cells containing TRAP and cathepsin K were identified histochemically and immunohistochemically, respectively. Results-Cathepsin K and TRAP were detected within the same cells, principally within the epiligamentous region and to a lesser extent in the core region of ruptured CCL. Numbers of cells containing TRAP and cathepsin K were significantly greater in ruptured CCL, compared with CCL from young or aged dogs, and numbers of such cells were greater in CCL from aged dogs, compared with those of young dogs. In aged dogs, small numbers of cells containing TRAP and cathepsin K were seen in intact CCL associated with ligament fascicles in which there was chondroid transformation of ligament fibroblasts and disruption of the extracellular matrix. Conclusion and Clinical Relevance-Ruptured CCL contain greater numbers of cells with the proteinases TRAP and cathepsin K than CCL from healthy, young, or aged dogs. Results suggest that cell-signaling pathways that regulate expression of these proteinases may form part of the mechanism that leads to upregulation of collagenolytic ligament remodeling and progressive structural failure of the CCL over time.

Objective-To describe neuroendocrine responses that develop in dogs subjected to prolonged periods of ventricular pacing. Animals-14 adult male hound-type dogs. Procedure-Samples were obtained and neuroendocrine responses measured before (baseline) and after 3 periods of ventricular pacing. A pacemaker was used to induce heart rates of 180, 200, and 220 beats/min (BPM). Each heart rate was maintained for 3 weeks before increasing to the next rate. Atrial natriuretic peptide, antidiuretic hormone, aldosterone, norepinephrine, epinephrine, and dopamine concentrations and plasma renin activity were measured. Severity of left ventricular compromise was estimated. Results-Shortening fraction decreased significantly with increasing heart rates (mean +/- SE, 35.5 +/- 1.4, 25.0 +/- 1.4, 19.5 +/- 1.9, and 12.2 +/- 2.3 for baseline, 180 BPM, 200 BPM, and 220 BPM, respectively). Atrial natriuretic peptide concentrations increased significantly at 180 BPM (44.1 +/- 3.0 pg/mL) and 200 BPM (54.8 +/- 5.5 pg/mL), compared with baseline concentration (36.8 +/- 2.6 pg/mL). Dopamine concentration increased significantly at 200 BPM (70.4 +/- 10.4 pg/mL), compared with baseline concentration (44.2 +/- 7.3 pg/mL). Norepinephrine concentrations increased significantly from baseline concentration (451 +/- 46.2 pg/mL) to 678 +/- 69.8, 856 +/- 99.6, and 1,003 +/- 267.6 pg/mL at 180, 200, and 220 BPM, respectively. Conclusions and Clinical Relevance-Dogs subjected to ventricular pacing for 9 weeks developed neuroendocrine responses similar to those that develop in humans with more chronic heart failure and, except for epinephrine concentrations, similar to those for dogs subjected to ventricular pacing for < 6 weeks.