Objective-To assess the effects of ketamine hydrochloride, propofol, or compounded thiopental sodium administration on intraocular pressure (IOP) and qualities of induction of and recovery from anesthesia in horses. Animals-6 healthy adult horses. Procedures-Horses were sedated with xylazine hydrochloride (0.5 mg/kg), and anesthesia was induced with guaifenesin followed by ketamine (2 mg/kg), propofol (3 mg/kg), or thiopental (4 mg/kg) in a crossover study with ≥ 1 week between treatments. For each horse, IOP in the right eye was measured with a handheld applanation tonometer before and after xylazine administration, at the time of recumbency, and every 3 minutes after induction of anesthesia until spontaneous movement was observed. Cardiorespiratory responses and venous blood measurements were recorded during anesthesia. Induction of and recovery from anesthesia were subjectively evaluated by investigators who were unaware of the anesthetic treatment of each horse. Data were analyzed via a repeated-measures ANOVA with Holm-Ŝidák post hoc comparisons. Results-Compared with findings after xylazine administration (mean +/- SD, 17 +/- 3 mm Hg), thiopental decreased IOP by 4 +/- 23%, whereas propofol and ketamine increased IOP by 8 +/- 11% and 37 +/- 16%, respectively. Compared with the effects of ketamine, propofol and thiopental resulted in significantly lower IOP at the time of recumbency and higher heart rates at 3 minutes after induction of anesthesia. No other significant differences among treatments were found. Conclusions and Clinical Relevance-These findings support the use of thiopental or propofol in preference to ketamine for horses in which increases in IOP should be minimized.

Objective-To evaluate the platelet activation response before and after treatment with clopidogrel in horses. Animals-12 healthy adult mares. Procedures-In a masked study, horses (6/group) were randomly allocated to alternately receive placebo or clopidogrel via nasogastric tube at a loading dose of 4 mg/kg followed by 2 mg/kg every 24 hours. Blood samples were collected before and 72 hours after initiation of treatment for ADP- and collagen-induced light transmission aggregometry; determination of closure time in collagen-ADP cartridges; modified thrombelastography for comparison of maximal amplitudes generated by kaolin, reptilase, and reptilase plus ADP activation; and flow cytometric tests to detect platelet fibrinogen binding, P-selectin expression, and phosphatidylserine externalization before and after ex vivo stimulation with thrombin, convulxin, thrombin with convulxin, and calcium ionophore. Results-Clopidogrel administration induced a significant decrease in mean aggregation response to 5μM and 10μM ADP stimulation; however, 2 horses had resistance to clopidogrel's inhibitory action. Significant differences after clopidogrel treatment were not found in any other tests of platelet function. Conclusions and Clinical Relevance-Assays using commercially available reagents were configured to measure different variables of the platelet activation response; however, clopidogrel's platelet inhibitory action was only detected by ADP-induced light transmission aggregometry. Results also suggested that horses, like humans, have interindividual variability in response to clopidogrel that may influence the drug's clinical efficacy as an antiplatelet agent.

Objective: To evaluate the effects of dorsal versus lateral recumbency on the cardiopulmonary system during isoflurane anesthesia in red-tailed hawks (Buteo jamaicensis). Animals: 6 adult 1.1- to 1.6-kg red-tailed hawks. Procedures: A randomized, crossover study was used to evaluate changes in respiratory rate, tidal volume, minute ventilation, heart rate, mean arterial and indirect blood pressures, and end-tidal Pco2 measured every 5 minutes plus Paco2 and Pao2 and arterial pH measured every 15 minutes throughout a 75-minute study period. Results: Respiratory rate was higher, tidal volume lower, and minute ventilation not different in lateral versus dorsal recumbency. Position did not affect heart rate, mean arterial blood pressure, or indirect blood pressure, although heart rate decreased during the anesthetic period. Birds hypoventilated in both positions and Paco2 differed with time and position × time interaction. The Petco2 position × time interaction was significant and Petco2 was a mean of 7 Torr higher than Paco2. The Paco2 in dorsal recumbency was a mean of 32 Torr higher than in lateral recumbency. Birds in both positions developed respiratory acidosis. Conclusions and Clinical Relevance: Differences in tidal volume with similar minute ventilation suggested red-tailed hawks in dorsal recumbency might have lower dead space ventilation. Despite similar minute ventilation in both positions, birds in dorsal recumbency hypoventilated more yet maintained higher Pao2, suggesting parabronchial ventilatory or pulmonary blood flow distribution changes with position. The results refute the hypothesis that dorsal recumbency compromises ventilation and O2 transport more than lateral recumbency in red-tailed hawks.

Objective—To evaluate the effect of ovariectomy on insulin sensitivity in horses and determine whether the effects of suppression of the hypothalamo-pituitary-adrenal axis differ before and after ovariectomy. Animals—6 healthy mares. Procedures—The horses underwent an IV glucose tolerance test (IVGTT), an insulin sensitivity test, and a dexamethasone suppression test before and 5 weeks after ovariectomy. Body weight, serum cortisol and plasma ACTH concentrations, serum insulin-to-blood glucose concentration ratios, and changes in blood glucose concentration with time after injection of glucose or insulin were compared before and after ovariectomy. Results—The dexamethasone injection resulted in a decrease in serum cortisol concentration before and after ovariectomy. In all horses, baseline plasma ACTH concentrations were within the reference range before and after ovariectomy. For each mare, results of an IVGTT before and after ovariectomy were considered normal. No significant differences in basal blood glucose concentration or time to reach baseline glucose concentration after an IVGTT were observed. Basal serum insulin concentration and serum insulin-to-blood glucose concentration ratios were not significantly different before or after ovariectomy, nor was the mean time to attain a 50% decrease in blood glucose concentration after insulin injection. Conclusions and Clinical Relevance—Results indicated that ovariectomy does not appear to modify dexamethasone response in horses and that it does not modify short-term measures of insulin sensitivity. Findings suggested that horses undergoing ovariectomy are not at higher risk of developing equine metabolic syndrome or hypothalamo-pituitary-adrenal axis dysfunction and associated morbidity.

Objective-To evaluate the use of CT and MRI for guidance of osteochondral sample collection for histologic detection of early osteoarthritic lesions in centrodistal (distal intertarsal) joints of horses. Sample -Right tarsal joints from the cadavers of 24 Icelandic horses aged 29 to 31 months. Procedures-CT and MRI were used to evaluate the extent of suspected osteoarthritic changes in centrodistal joints, which were graded with a semiquantitative system. The anatomic regions with the highest grade of change were identified, and osteochondral samples were obtained from these regions. Samples were also obtained from the same centrodistal joints at predetermined sites. Histologic examination of all samples was performed, with samples classified as negative or positive for osteoarthritis, and results were compared between sample collection methods. Results-Histologic examination revealed osteoarthritic lesions in 29% (7/24) of centrodistal joints with the predetermined method and in 63% (15/24) with the image-guided method. Significant associations were identified between histologic osteoarthritis detection and the summed image-guided sample collection site image grades, central osteophytes, articular cartilage thickness abnormalities, grade 2 articular mineralization front defects, and grade 2 marginal osteophytes. Conclusions and Clinical Relevance-CT and MRI aided the detection of focal changes suggestive of early-stage osteoarthritis in the centrodistal joints of equine cadavers and may be useful for detection of similar disease in live horses. The first morphological changes of centrodistal joint osteoarthritis were suspected to be in the articular cartilage and the articular mineralization front regions.

Objective-To assess antimicrobial resistance and transfer of virulence genes facilitated by subtherapeutic concentrations of antimicrobials in swine intestines. Animals-20 anesthetized pigs experimentally inoculated with donor and recipient bacteria. Procedures-4 recipient pathogenic bacteria (Salmonella enterica serotype Typhimurium, Yersinia enterocolitica, Shigella flexneri, or Proteus mirabilis) were incubated with donor bacteria in the presence of subinhibitory concentrations of 1 of 16 antimicrobials in isolated ligated intestinal loops in swine. Donor Escherichia coli contained transferrable antimicrobial resistance or virulence genes. After coincubations, intestinal contents were removed and assessed for pathogens that acquired new antimicrobial resistance or virulence genes following exposure to the subtherapeutic concentrations of antimicrobials. Results-3 antimicrobials (apramycin, lincomycin, and neomycin) enhanced transfer of an antimicrobial resistance plasmid from commensal E coli organisms to Yersinia and Proteus organisms, whereas 7 antimicrobials (florfenicol, hygromycin, penicillin G, roxarsone, sulfamethazine, tetracycline, and tylosin) exacerbated transfer of an integron (Salmonella genomic island 1) from Salmonella organisms to Yersinia organisms. Sulfamethazine induced the transfer of Salmonella pathogenicity island 1 from pathogenic to nonpathogenic Salmonella organisms. Six antimicrobials (bacitracin, carbadox, erythromycin, sulfathiazole, tiamulin, and virginiamycin) did not mediate any transfer events. Sulfamethazine was the only antimicrobial implicated in 2 types of transfer events. Conclusions and Clinical Relevance-10 of 16 antimicrobials at subinhibitory or subtherapeutic concentrations augmented specific antimicrobial resistance or transfer of virulence genes into pathogenic bacteria in isolated intestinal loops in swine. Use of subtherapeutic antimicrobials in animal feed may be associated with unwanted collateral effects.

Objective: To evaluate the effectiveness of reduction of inspired oxygen fraction (Fio2) or application of positive end-expiratory pressure (PEEP) after an alveolar recruitment maneuver (ARM) in minimizing anesthesia-induced atelectasis in dogs. Animals: 30 healthy female dogs. Procedures: During anesthesia and neuromuscular blockade, dogs were mechanically ventilated under baseline conditions (tidal volume, 12 mL/kg; inspiratory-to-expiratory ratio, 1:2; Fio2, 1; and zero end-expiratory pressure [ZEEP]). After 40 minutes, lungs were inflated (airway pressure, 40 cm H2O) for 20 seconds. Dogs were then exposed to baseline conditions (ZEEP100 group), baseline conditions with Fio2 reduced to 0.4 (ZEEP40 group), or baseline conditions with PEEP at 5 cm H2O (PEEP100 group; 10 dogs/group). For each dog, arterial blood gas variables and respiratory system mechanics were evaluated and CT scans of the thorax were obtained before and at 5 (T5) and 30 (T30) minutes after the ARM. Results: Compared with pre-ARM findings, atelectasis decreased and Pao2:Fio2 ratio increased at T5 in all groups. At T30, atelectasis and oxygenation returned to pre-ARM findings in the ZEEP100 group but remained similar to T5 findings in the other groups. At T5 and T30, lung static compliance in the PEEP100 group was higher than values in the other groups. Conclusions and Clinical Relevance: Application of airway pressure of 40 cm H2O for 20 seconds followed by Fio2 reduction to 0.4 or ventilation with PEEP (5 cm H2O) was effective in diminishing anesthesia-induced atelectasis and maintaining lung function in dogs, compared with the effects of mechanical ventilation providing an Fio2 of 1.

Objective: To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. Animals: 26 athymic nude rats. Procedures: 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Results: Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. Conclusions and Clinical Relevance: The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

Objective-To evaluate the antinociceptive and sedative effects and duration of action of hydromorphone hydrochloride after IM administration to American kestrels (Falco sparverius). Animals-11 healthy 2-year-old American kestrels. Procedures-Hydromorphone (0.1, 0.3, and 0.6 mg/kg) and an equivalent volume of saline (0.9% NaCl) solution (control treatment) were administered IM to kestrels in a masked randomized complete crossover study design. Foot withdrawal response to a thermal stimulus was determined 30 to 60 minutes before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were determined 3 to 5 minutes before each thermal test. Results-Hydromorphone at 0.6 mg/kg, IM, significantly increased the thermal foot withdrawal threshold, compared with the response after administration of saline solution, for up to 3 hours, and hydromorphone at 0.1, 0.3, and 0.6 mg/kg, IM, significantly increased withdrawal responses for up to 6 hours, compared with baseline values. No significant differences in mean sedation-agitation scores were detected between hydromorphone and saline solution treatments; however, appreciable sedation was detected in 4 birds when administered 0.6 mg of hydromorphone/kg. Conclusions and Clinical Relevance-Hydromorphone at the doses evaluated significantly increased the thermal nociception threshold for American kestrels for 3 to 6 hours. Additional studies with other types of stimulation, formulations, dosages, routes of administration, and testing times are needed to fully evaluate the analgesic and adverse effects of hydromorphone in kestrels and other avian species and the use of hydromorphone in clinical settings.

Objective—To determine the magnitude and location of skin movement attributable to the cutaneus trunci muscle reflex in response to localized stimulation of the skin of the dorsolateral aspect of the thoracic wall in horses. Animals—8 horses. Procedures—A grid of 56 reflective markers was applied to the lateral aspect of the body wall of each horse; markers were placed at 10-cm intervals in 7 rows and 8 columns. A motion analysis system with 10 infrared cameras was used to track movements of the markers in response to tactile stimulation of the dorsolateral aspect of the thoracic wall at the levels of T6, T11, and T16. Marker movement data determined after skin stimulation were used to create a skin deformation gradient tensor field, which was analyzed with custom software. Results—The sites of maximal skin deformation were located close to the stimulation sites; the centers of the twitch responses were located a mean distance of 7.7 to 12.8 cm ventral and between 6.6 cm cranial and 3.1 cm caudal to the stimulation sites. Conclusions and Clinical Relevance—Findings of this study may have implications for assessment of nerve conduction velocities of the cutaneus trunci muscle reflex and may enhance understanding of the responses of horses to placement of tack or other equipment on skin over the cutaneus trunci muscles.