Objective-To compare renal clearance of technetium Tc 99m pentetate with plasma clearance by use of a glomerular filtration rate technique in pigs from 3 to 24 weeks of age. Animals-24 female pigs. Procedure-At the time of investigation, 5 pigs were 3 weeks old, 6 pigs were 6 weeks old, 8 pigs were 12 weeks old, and 5 pigs were 24 weeks old. Plasma clearance of technetium Tc 99m pentetate was measured by the use of a single injection technique followed by collection of multiple blood samples until 5 hours after the injection. Simultaneously, urine was collected through a urinary catheter, and the renal clearance of technetium Tc 99m pentetate was calculated. Results-Plasma clearance of technetium Tc 99m pentetate was correlated with the renal clearance ( r = 0.95). Plasma clearance was higher than renal clearance at all ages (mean, 5.8%), indicating extrarenal clearance of technetium Tc 99m pentetate or methodologic errors. Volume of distribution increased with increasing age but decreased as a fraction of body weight. Conclusions-Plasma clearance of technetium Tc 99m pentetate estimates renal clearance with acceptable precision when using single injection technique and multiple blood samples in pigs from 3 to 24 weeks of age.

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 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 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.

Objective-To develop a laparoscopic-assisted technique for cystopexy in dogs. Animals-8 healthy male dogs, 7 healthy female dogs, and 3 client-owned dogs with retroflexion of the urinary bladder secondary to perineal herniation. Procedure-Dogs were anesthetized, and positive pressure ventilation was provided. In the healthy male dogs, the serosal surface of the bladder was sutured to the abdominal wall. In the healthy female dogs, the serosa and muscular layer of the bladder were incised and sutured to the aponeurosis of the external and internal abdominal oblique muscles. Dogs were monitored daily for 30 days after surgery. Results-All dogs recovered rapidly after surgery and voided normally. In the female dogs, results of urodynamic (leak point pressure and urethral pressure profilometry) and contrast radiographic studies performed 30 days after surgery were similar to results obtained before surgery. Cystopexy was successful in all 3 client-owned dogs, but 1 of these dogs was subsequently euthanatized because of leakage from a colopexy performed at the same time as the cystopexy. Conclusion and Clinical Relevance-The laparoscopic-assisted cystopexy technique was quick, easy to perform, and not associated with urinary tract infection or abnormalities of urination.

Detection of the scrapie-associated protease-resistant prion protein (PrPres) in sheep brains in the early phase after intracerebral inoculation of the scrapie agent has not been documented. Fourteen 4-mo-old, genetically susceptible lambs (QQ homozygous at codon 171 of the PrP gene) were obtained for this study. Twelve lambs were inoculated intracerebrally with a brain suspension from sheep naturally affected with scrapie, and 2 served as uninoculated controls. Two inoculated animals were euthanized at each of 6 times postinoculation (1 h to 6 wk), and their brains were collected for histopathological study, for detection of PrPres by the Western blot technique and an immunohistochemical (IHC) method, and for the detection of scrapie-associated fibrils (SAF) by negatively stained electron microscopy (EM). Microscopic lesions associated with introduction of the inoculum were seen in the brains of inoculated animals at all 6 times. However, both the Western blot and IHC techniques did not detect PrPres after the initial 3 d postinoculation, nor did EM detect SAF in any of the samples. From these findings, it is presumed that until host amplification has occurred, the concentration of PrPres in inoculum is insufficient for detection by currently available techniques.

Objective-To evaluate splenic mast cell tumors (MCT) of cats for activating mutations in the protooncogene c-kit. Sample Population-10 formalin-fixed, paraffinembedded splenic MCT from cats in the pathology database of the Veterinary Medical Teaching Hospital at the University of California, Davis. Procedure-Genomic DNA was isolated from tumor specimens, and the polymerase chain reaction (PCR) procedure was performed for exons 11, 12, and 17. The PCR products were analyzed by use of agarose gel electrophoresis and then directly sequenced. Results-We did not identify mutations in the juxtamembrane domain (encoded by exons 11 and 12) or catalytic domain (encoded by exon 17) of c-kit in any of the splenic MCT specimens. Conclusions and Clinical Relevance-Although mutations in the proto-oncogene c-kitoccur frequently in naturally developing MCT in dogs and aggressive mastocytosis in humans, the data reported here documented that dysregulation of Kit function through activating mutations is unlikely in splenic MCT of cats. Therapeutic strategies aimed at inhibiting Kit signaling (ie, kinase inhibitors such as imatinib [STI571]) may not be of benefit for the treatment of this disease in cats.

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.