Objective-To compare cardiopulmonary responses during anesthesia maintained with halothane and responses during anesthesia maintained by use of a total intravenous anesthetic (TIVA) regimen in horses. Animals-7 healthy adult horses (1 female, 6 geldings). Procedure-Each horse was anesthetized twice. Romifidine was administered IV, and anesthesia was induced by IV administration of ketamine. Anesthesia was maintained for 75 minutes by administration of halothane (HA) or IV infusion of romifidine, guaifenesin, and ketamine (TIVA). The order for TIVA or HA was randomized. Cardiopulmonary variables were measured 40, 60, and 75 minutes after the start of HA or TIVA. Results-Systolic, diastolic, and mean carotid arterial pressures, velocity time integral, and peak acceleration of aortic blood flow were greater, and systolic, diastolic, and mean pulmonary arterial pressure were lower at all time points for TIVA than for HA. Pre-ejection period was shorter and ejection time was longer for TIVA than for HA. Heart rate was greater for HA at 60 minutes. Minute ventilation and alveolar ventilation were greater and inspiratory time was longer for TIVA than for HA at 75 minutes. The PaCO2 was higher at 60 and 75 minutes for HA than for TIVA. Conclusions and Clinical relevance-Horses receiving a constant-rate infusion of romifidine, guaifenesin, and ketamine maintained higher arterial blood pressures than when they were administered HA. There was some indication that left ventricular function may be better during TIVA, but influences of preload and afterload on measured variables could account for some of these differences.

Objective-To use computed tomography (CT) to provide a detailed description of elbow joint structures in clinically normal dogs. Animals-6 clinically normal adult mixed-breed dogs weighing 24 to 37 kg and one 12-month-old Labrador Retriever weighing 27 kg. Procedure-To perform CT of both elbow regions, dogs were anesthetized and placed in lateral recumbency. One- and 2-mm contiguous slices were obtained by use of a third generation computed tomographic scanner. Good resolution and anatomic detail were acquired from the computed tomographic images by use of a bone (window width, 3,500 Hounsfield units; window level, 500 Hounsfield units) and soft-tissue setting (window width, 400 Hounsfield units; window level, 66 Hounsfield units). After euthanasia, the forelimbs from the Labrador Retriever were removed and frozen in water at -18oC. Elbow joints were sectioned into approximately 1- mm-thick slab sections by use of an electric planer. Anatomic sections were photographed and compared with the corresponding computed tomographic images. Computed tomographic reconstructions of the elbow joint were created in sagittal and dorsal planes. Results-Structures on the computed tomographic images were matched with structures in the corresponding anatomic sections. The entire humeroradioulnar joint surface could be evaluated on the reconstructed images in the sagittal and dorsal plane. Conclusions and Clinical Relevance-Computed tomographic images provide full anatomic detail of the bony structures of the elbow joint in dogs. Muscles, large blood vessels, and nerves can also be evaluated. These results could be used as a basis for evaluation of computed tomographic images of the forelimbs of dogs with elbow joint injuries.

Objective-To determine significant molecular and cellular factors responsible for differences in secondintention healing in thoracic and metacarpal wounds of horses. Animals-6 adult mixed-breed horses. Procedure-A full-thickness skin wound on the metacarpus and another such wound on the pectoral region were created, photographed, and measured, and tissue was harvested from these sites weekly for 4 weeks. Gene expression of type-I collagen, transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-1, and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by quantitative in situ hybridization. Myofibroblasts were detected by immunohistochemical labeling with α-smooth muscle actin (α-SMA). Collagen accumulation was detected by use of picrosirius red staining. Tissue morphology was examined by use of H&E staining. Results-Unlike thoracic wounds, forelimb wounds enlarged during the first 2 weeks. Myofibroblasts, detected by week 1, remained abundant with superior organization in thoracic wounds. Type-I collagen mRNA accumulated progressively in both wounds. More type-I collagen and TGF-β1 mRNA were seen in forelimb wounds. Volume of MMP-1 mRNA decreased from day 0 in both wounds. By week 3, TIMP-1 mRNA concentration was greater in thoracic wounds. Conclusions and Clinical Relevance-Greater collagen synthesis in metacarpal than thoracic wounds was documented by increased concentrations of myofibroblasts, type-I collagen mRNA, TGF-β1 mRNA, and decreased collagen degradation (ie, MMP-1). Imbalanced collagen synthesis and degradation likely correlate with development of exuberant granulation tissue, delaying healing in wounds of the distal portions of the limbs. Factors that inhibit collagen synthesis or stimulate collagenase may provide treatment options for horses with exuberant granulation tissue.

Objective-To determine whether small intestinal ischemia and reperfusion induces bacterial translocation and proinflammatory cytokine response in either the systemic or portal circulation in dogs. Animals-17 healthy adult Beagles. Procedure-The superior mesenteric artery (SMA) was occluded for 0 (group-3 dogs), 30 (group-1 dogs), or 60 (group-2 dogs) minutes, followed by reperfusion for 180 minutes; serum lactate and endotoxin concentrations and tumor necrosis factor-alpha (TNF-alpha), interleukin- 1beta (IL-1beta), and IL-6 activities in the systemic and portal circulation and intramucosal pH were measured at various time points. Results-In group-2 dogs, TNF-alpha activity was found to be significantly increased in the portal circulation, peaking at 60 minutes of reperfusion; TNF-alpha activity, in the systemic circulation, gradually increased from 60 minutes of reperfusion to the end of the experiment; however, the increase was not significant. In group-1 and -2 dogs, IL-6 activities significantly and gradually increased in the systemic and portal circulation during the reperfusion phase, and the magnitude of these increases was dependent on the duration of the ischemic phase. There were no significant changes in IL-1beta activity or endotoxin concentration in any dog group. Conclusions and Clinical Relevance-Results of the our study indicate that intestinal ischemia and reperfusion leads to significant increases of the circulating TNF-alpha and IL-6 activities, depending on the duration of the ischemia phase, in the absence of detectable endotoxin in the circulation. This finding suggests that intestinal ischemia and reperfusion induces a systemic proinflammatory cytokine response in dogs.

Objective-To assess gastric tone in the proximal portion of the stomach in horses during and after ingestion of 4 diets (2 diets of grain and 2 diets of hay). Animals-6 adult horses. Procedure-A polyester bag with a volume of approximately 1,600 ml was inserted through a gastric cannula into the proximal portion of the stomach of each horse. Internal pressure of the bag was maintained at 2 mm Hg by use of an electronic barostat, and changes in bag volume were recorded before, during, and after horses consumed diets of grain or hay. Each horse was fed 0.5 and 1.0 g of grain/kg and 0.5 and 1.0 g of hay/kg. Changes in bag volume measured by use of the barostat were indirectly related to changes in tone of the gastric wall. Results-Food intake caused a distinctly significant biphasic increase in volume. The first phase was during active ingestion, which was followed shortly by a second, more prolonged postprandial phase. The ingestion-related phase of the response to intake of a diet of 1 g of hay/kg was significantly greater than that for the other diets. Conclusion and Clinical Relevance-Ingestion of a solid meal induces a biphasic relaxation response in the proximal portion of the stomach of horses. Magnitude of the ingestion-related phase may be determined by size of the meal.

Objective-To determine tracheal mucociliary clearance rate (TMCCR) by use of a standard protocol in healthy anesthetized cats and to determine the effect of theophylline on TMCCR in healthy anesthetized cats. Animals-6 healthy cats. Procedure-Cats were anesthetized with propofol, and a droplet of the radiopharmaceutical technetium Tc 99m macroaggregated albumin was placed endoscopically at the carina. Dynamic acquisition scintigraphic imaging was performed, using the larynx as the end point. The TMCCR was determined by measuring the distance the droplet traveled by frame rate. Each cat was imaged 6 times as follows: 3 times following placebo administration and 3 times following the administration of sustained release theophylline (25 mg/kg, PO). Serum theophylline concentrations were assessed during imaging to ensure therapeutic concentrations. Results-The TMCCR in healthy adult cats anesthetized with propofol was 22.2 +/- 2.8 mm/min. Tracheal mucociliary clearance rate in cats receiving theophylline was 21.8 +/- 3.5 mm/min. Theophylline administration did not significantly alter TMCCR. Conclusion and Clinical Relevance-Theophylline has been shown to increase TMCCR in humans and dogs. In our study, we determined TMCCR in healthy anesthetized cats and found that it was not accelerated by the administration of theophylline.

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.

Objective-To evaluate effects of age and body size of dogs on intestinal permeability (unmediated diffusion) as measured by the ratio of urinary lactulose to L-rhamnose (L:R) and absorption (carrier-mediated transport) as measured by the ratio of urinary D-xylose to 3-O-methyl-D-glucose (X:MG) and to determine whether these variables correlated with fecal quality. Animals-6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. Procedure-A solution that contained lactulose and rhamnose or xylose and 3-O-methyl-D-glucose was administered orally to dogs that were 12, 22, 36, and 60 weeks old. Urine was collected 6 hours later, and urinary L:R and X:MG were calculated. Fecal moisture and scoring were recorded during the same periods. Results-Age and breed did not affect intestinal absorption, and we did not detect a relationship between X:MG and fecal variables. In contrast, we detected significant effects of age and body size on intestinal permeability. Puppies (12 weeks old) and large dogs had higher intestinal permeability than adult (60 weeks old) and small dogs. The increased intestinal permeability in large dogs was associated with lower fecal quality as indicated by the significant positive correlations between L:R and fecal moisture (r, 0.61) and L:R and fecal scores (r, 0.86) in adult dogs. Conclusion and Clinical Relevance-These results indicate that age and body size should be considered when assessing intestinal permeability by use of the L:R urinary excretion test in dogs. High intestinal permeability could be a possible cause of poor fecal quality in large dogs.

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 identify and characterize motilin receptors in equine duodenum, jejunum, cecum, and large colon and to determine whether erythromycin lactobionate competes with porcine motilin for binding to these receptors. Sample Population-Specimens of various segments of the intestinal tracts of 4 adult horses euthanatized for reasons unrelated to gastrointestinal tract disease. Procedure-Cellular membranes were prepared from smooth muscle tissues of the duodenum, jejunum, pelvic flexure, and cecum. Affinity and distribution of motilin binding on membrane preparations were determined by use of 125I-labeled synthetic porcine motilin. Displacement studies were used to investigate competition between 125I-labeled synthetic porcine motilin and erythromycin lactobionate for binding to motilin receptors in various segments of bowel. Results-Affinity of 125I-labeled synthetic porcine motilin for the equine motilin receptor was estimated to be 6.1nM. A significantly higher number of motilin receptors was found in the duodenum than in the pelvic flexure and cecum. The jejunum had a significantly higher number of motilin receptors than the cecum. Erythromycin lactobionate displacement of 125I-labeled porcine motilin from the equine motilin receptor did not differ significantly among various segments of bowel. Conclusions and Clinical Relevance-Motilin receptors were found in the duodenum, jejunum, pelvic flexure, and cecum of horses. The highest number of motilin receptors was in the duodenum, and it decreased in more distal segments of bowel. Erythromycin lactobionate competed with motilin binding in the equine gastrointestinal tract. This suggests that 1 of the prokinetic actions of erythromycin in horses is likely to be secondary to binding on motilin receptors.