Objectives-To evoke and measure the nociceptive withdrawal reflex (NWR) by use of electromyographic recordings and to score the behavioral nociceptive responses to electrical pulses in standing nonsedated horses. Animals-10 adult horses. Procedure-The lateral palmar digital nerve of the forelimb was transcutaneously stimulated, and surface electromyographic responses were recorded from the ulnaris lateralis, extensor carpi radialis, and common digital extensor muscles. Stimuli consisted of a 25-millisecond train of 5 constant-current pulses delivered by a computer-controlled stimulator. The 80- to 250-milliseconds poststimulation interval was analyzed to detect the NWR. The current intensity was increased in steps of 0.5 mA until the NWR threshold intensity (It) was reached. The stimulus at It was repeated twice. Latency and amplitude of the NWR, together with the behavioral reaction of horses, were analyzed. The latter was scored according to a scale from 0 (no reaction) to 5 (vigorous reaction). Finally, 3 suprathreshold stimuli at 1.2 × It were analyzed. Results-The median It to elicit NWR was 2.5 mA. Median onset latency of the NWR was 96.0 milliseconds at It and 89.6 milliseconds for suprathreshold stimuli. The amplitude of the reflexes was higher for suprathreshold stimulations, and behavioral reactions were slightly stronger when stimulus intensity increased. Conclusions and Clinical Relevance-Results of our study indicate that it is possible to record NWR in conscious standing horses, to define a reflex threshold, and to measure reflexes in response to increasing stimulus intensity.

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 develop an endoscopic technique for use in monitoring devlopment of gastric ulcers via a gastric cannula during withholding of feed and administration of a finely ground diet to pigs. Animals-6 pigs weighing between 60 and 70 kg. Procedure-A gastric cannula was surgically inserted adjacent to the pars esophagea in each pig. Pigs were fed a finely ground diet for two 7-day periods that were separated by a 48-hour period during which feed was withheld. Endoscopic examination via the gastric cannula was used to monitor development of ulcers in the pars esophageal region of the pigs during the 48-hour period of feed withhold and subsequent 7-day feeding period. An ulcer score was assigned during each endoscopic examination. A final examination was performed during necropsy and compared with results for the final endoscopic examination. Results-Consumption of a finely ground diet for 7 days resulted in progressive erosive damage to the pars esophageal region of the stomach. Further significant increases in ulcerative damage were detected after 24 and 48 hours of withholding of feed. Final examination during necropsy did not reveal significant differences from results obtained during the final endoscopic examination. Conclusions and Clinical Relevance-Endoscopic examination via a gastric cannula was an effective means of monitoring ulcer development in the pars esophagea of pigs. Feeding a finely ground diet and withholding of feed induced endoscopically observable ulcers in the stratified squamous epithelial region of the stomach. Direct visual examination during necropsy confirmed the accuracy of endoscopic examination.

Objective-To investigate accumulation of extracellular adenosine (ADO) by equine articular chondrocytes and to compare effects of adenosine kinase inhibition and adenosine deaminase inhibition on the amount of nitric oxide (NO) produced by lipopolysaccharide (LPS)-stimulated chondrocytes. Sample Population-Articular cartilage from metacarpophalangeal and metatarsophalangeal joints of 14 horses. Procedure-Chondrocytes were cultured as monolayers, and cells were incubated with LPS, the adenosine kinase inhibitor 5'-iodotubercidin (ITU), or the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3- nonyl)adenine hydrochloride (EHNA). Concentrations of ADO in cell supernatants were measured by use of reverse-phase high-performance liquid chromatography. Effect of inhibition of enzymatic metabolism of ADO on induced NO production was evaluated by exposing cells to a combination of LPS and ITU or LPS and EHNA. Results-Articular chondrocytes accumulated extracellular ADO when exposed to LPS or ITU. Chondrocytes exposed to ITU accumulated ADO in a time-dependent manner. Unstimulated chondrocytes did not accumulate ADO. Similarly, EHNA alone did not produce detectable ADO concentrations; however, addition of EHNA and ITU resulted in a synergistic effect on accumulation of ADO. Lipopolysaccharideinduced NO production was more effectively suppressed by exposure to ITU than to EHNA Conclusions and Clinical Relevance-Equine articular chondrocytes release ADO in response to the proinflammatory stimulus of bacterial LPS. Inhibition of the metabolism of ADO increases accumulation of extracellular ADO. Autocrine release of ADO from chondrocytes may play a role in the cellular response to tissue damage in arthritic conditions, and pharmacologic modulation of these pathways in joints of arthritic horses could be a potential method of therapy.

Objective-To evaluate whether immunosuppressive doses of cyclosporine (CsA) have an adverse effect on the liver, kidney, and pancreatic beta cells of pigs. Animals-8 juvenile 8-week-old Landrace X Large White crossbred pigs. Procedure-CsA (100 to 140 mg/kg) was administered orally to euglycemic pigs to reach whole blood trough concentrations of approximately 1500 ng/mL. To determine pancreatic beta cell function, plasma Cpeptide and insulin concentrations were measured in response to IV administration of glucose, glucagon, arginine, and oral administration of glucose. Effects on liver and kidney were determined by monitoring serum measurements of liver function and serum creatinine concentrations, respectively. Results-Plasma concentrations of C-peptide were significantly lower in euglycemic CsA-treated pigs, compared with control pigs, following IV administration of glucose, glucagon, arginine, and oral administration of glucose. Furthermore, the glucose clearance rate was decreased in euglycemic CsA-treated pigs, compared with control pigs. Serum creatinine concentrations and 4 of 7 serum measurements of liver function were not adversely affected by CsA administration. Serum concentrations of bilirubin and albumin were significantly increased, and serum alanine aminotransferase activity was significantly decreased in CsA-treated pigs, compared with control pigs. Histologic evaluation of liver and kidney sections revealed no pathologic findings in CsA-treated or control pigs. Conclusions and Clinical Relevance-In our study, immunosuppressive doses of CsA caused an impairment of porcine pancreatic beta cell function, but did not have toxic effects on the kidney. However, on the basis of changes in serum bilirubin and albumin concentrations and alanine aminotransferase activity, subclinical toxic effects on the liver did occur when immunosuppressive doses of CsA were administered.

Objective- To determine the hemodynamic effects of IM administration of romifidine hydrochloride in propofol-anesthetized cats. Animals-15 adult domestic shorthair cats. Procedure-Cats were randomly assigned to receive romifidine (0, 400, or 2,000 µg/kg, IM). Cats were anesthetized with propofol and mechanically ventilated with oxygen. The right jugular vein, left carotid artery, and right femoral artery and vein were surgically isolated and catheterized. Heart rate; duration of the PR, QRS, and QT intervals; mean pulmonary artery pressure; mean right atrial pressure; systolic, diastolic, and mean arterial pressures; left ventricular systolic pressure; left ventricular end-diastolic pressure; and cardiac output were monitored. Systemic vascular resistance, rate of change of left ventricular pressure, and rate pressure product were calculated. Arterial and venous blood samples were collected anaerobically for determination of pH and blood gas tensions (PO2 and PCO2). Results-Administration of romifidine at 400 and 2,000 µg/kg, IM, decreased heart rate, cardiac output, rate of change of left ventricular pressure, rate pressure product, and pH. Arterial and pulmonary artery pressures, left ventricular pressure, left ventricular end-diastolic pressure, and right atrial pressure increased and then gradually returned to baseline values. Arterial blood gas values did not change, whereas venous PCO2 increased and venous PO2 decreased. Significant differences between low and high dosages were rare, suggesting that the dosages investigated produced maximal hemodynamic effects. Conclusion and Clinical Relevance-Romifidine produces cardiovascular effects that are similar to those of other α2-agonists. High dosages of romifidine should be used with caution in cats with cardiovascular compromise.

Objective-To develop laparoscopic-assisted techniques for enterostomy feeding tube placement and full-thickness biopsy of the jejunum in dogs. Animals-15 healthy dogs. Procedure-Dogs were anesthetized, and positive pressure ventilation was provided. A trocar cannula for the laparoscope was inserted on the ventral midline caudal to the umbilicus. For enterostomy tube placement, a second trocar cannula was placed lateral to the right rectus abdominis muscle, and a Babcock forceps was used to grasp the duodenum and elevate it to the incision made for the cannula. The duodenum was sutured to the abdominal wall, and a feeding tube was inserted. For jejunal biopsy, a third trocar cannula was placed lateral to the left rectus abdominis muscle. A portion of jejunum was elevated to the incision for the second or third cannula, and a full-thickness biopsy specimen was obtained. A second specimen was obtained from another portion of jejunum, and retention sutures for the 2 biopsy sites were tied so that serosal surfaces of the biopsy sites were apposed to each other. Dogs were euthanatized 30 days after surgery. Results-The enterostomy tube was properly positioned and functional in all 8 dogs that underwent laparoscopic-assisted enterostomy tube placement, and sufficient samples for histologic examination were obtained from all 7 dogs that underwent laparoscopic-assisted jejunal biopsy. None of the dogs had any identifiable problems after surgery. Conclusion and Clinical Relevance-Results suggest that in dogs, laparoscopic-assisted procedures for enterostomy tube placement and jejunal biopsy are an acceptable alternative to procedures performed during a laparotomy.

Objective-To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. Animals-12 healthy, female, spayed cats. Procedure-Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. Results-All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. Conclusions and Clinical Relevance-Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.

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 investigate the effects of preexisting FeLV infection or FeLV and feline immunodeficiency (FIV) coinfection on the pathogenicity of the small variant of Haemobartonella felis (Hfsm, California variant) in cats. Animals-20 FeLV infected, 5 FeLV-FIV coinfected, and 19 retrovirus-free cats. Procedure-A client-owned cat, coinfected with FeLV and Hfsm, was the source for Hfsm. Inoculum 1 (FeLV free) was obtained by passage of source Hfsm through 4 FeLV-resistant cats. Inoculum 2 was obtained by further passage of Hfsm (inoculum 1) through 2 specific pathogenfree cats. Results-A mild-to-moderate anemia started 21 days after inoculation, with its nadir occurring at 35 to 42 days after inoculation. Infection with Hfsm induced greater decrease in hemoglobin concentration in FeLV infected cats, compared with retrovirus free cats. Reticulocytosis, macrocytosis, and polychromasia of erythrocytes developed in anemic cats regardless of retrovirus infection status. Mean neutrophil counts decreased during the hemolytic episode. For most cats, the anemia was transient. Four FeLV infected cats, 1 of which was also FIV infected, developed fatal FeLV-associated myeloproliferative diseases. Of the surviving cats, 8 died over the next 24 months from other FeLV-related diseases. Hemolysis did not recur after the initial episode. Inoculum 1 induced more severe anemia than inoculum 2. Conclusions and Clinical Relevance-Our results support the clinical observation that cats coinfected with FeLV and H felis develop more severe anemia than cats infected with H felis alone. Infection with Hfsm may induce myeloproliferative disease in FeLV infected cats. The small variant of H felis may lose pathogenicity by passage through FeLV-free cats.