Objective—To directly assess microcirculatory changes associated with induced hemorrhagic shock by use of sidestream dark field microscopy (SDM) and correlate those values with concurrently measured macrovascular and blood gas variables in healthy anesthetized dogs. Animals—12 adult dogs. Procedures—Dogs were anesthetized and splenectomized. Instrumentation and catheterization were performed for determination of macrohemodynamic and blood gas variables. Hemorrhagic shock was induced via controlled hemorrhage to a mean arterial blood pressure (MAP) of 40 mm Hg. Dogs were maintained in the shock state (MAP, 35 to 45 mm Hg) for 60 minutes. An SDM device was used to image microcirculation of buccal mucosa, and vascular analysis software was used to determine microcirculatory variables. These values were compared with other cardiovascular and blood gas variables to determine correlations. Results—Following hemorrhage, there was a significant decrease in microvascular variables (mean ± SD), including proportion of perfused vessels (82.77 ± 8.32% vs 57.21 ± 28.83%), perfused vessel density (14.86 ± 2.64 mm/m2 vs 6.66 ± 4.75 mm/m2), and microvascular flow index (2.54 ± 0.52 vs 1.59 ± 0.85). Perfused vessel density individually correlated well with macrovascular variables, with heart rate (zero order, partial correlation, and part correlation coefficients = −0.762, −0.884, and −0.793, respectively) and oxygen extraction ratio (−0.734, −0.832, and −0.746, respectively) being the most important predictors. Conclusions and Clinical Relevance—SDM allowed real-time imaging of the microvasculature and has potential as an effective tool in experimental and clinical applications for monitoring microcirculatory changes associated with hemorrhagic shock and resuscitation in dogs.

This project evaluated the use of an ingestible temperature sensor to measure body core temperature (Tc) in exercising dogs. Twenty-five healthy, unconditioned Labrador retrievers participated in an outdoor 3.5-km run, completed in 20 min on a level, 400-m grass track. Core temperature was measured continuously with a telemetric monitoring system before, during, and after the run. Data were successfully collected with no missing data points during the exercise. Core temperature elevated in the dogs from 38.7 +/- 0.3 degrees C at pre-exercise to 40.4 +/- 0.6 degrees C post-exercise. While rectal temperatures are still the standard of measurement, telemetric core temperature monitors may offer an easier and more comfortable means of sampling core temperature with minimal human and mechanical interference with the exercising dog.

Objective—To evaluate and compare circulating concentrations of islet amyloid polypeptide (IAPP), insulin, and glucose in nondiabetic cats classified by body condition score (BCS) and in cats with naturally occurring diabetes mellitus. Animals—109 (82 nondiabetic, 21 nonketoacidotic diabetic, and 6 ketoacidotic diabetic) cats. rocedures—Cats were examined and BCSs were assessed on a scale of 1 to 9. After food was withheld for 12 hours, blood was collected and plasma concentrations of IAPP and serum concentrations of insulin and glucose were measured. Differences in these values were evaluated among nondiabetic cats grouped according to BCS and in diabetic cats grouped as ketoacidotic or nonketoacidotic on the basis of clinicopathologic findings. Correlations were determined among variables. Results—In nondiabetic cats, BCS was significantly and positively correlated with circulating IAPP and insulin concentrations. Mean plasma IAPP concentrations were significantly different between cats with BCSs of 5 and 7, and mean serum insulin concentrations were significantly different between cats with BCSs of 5 and 8. Serum glucose concentrations were not significantly different among nondiabetic cats. Mean IAPP concentrations were similar between nonketoacidotic diabetic cats and nondiabetic cats with BCSs of 8 or 9. Mean IAPP concentrations were significantly reduced in ketoacidotic diabetic cats, compared with those of nondiabetic cats with BCSs of 6 through 8 and of nonketoacidotic diabetic cats. Conclusions and Clinical Relevance—Results indicated that increased BCS (a measure of obesity) is associated with increased circulating concentrations of IAPP and insulin in nondiabetic cats.

Objective—To determine magnetic resonance imaging (MRI) vertebral ratio values representing vertebral canal height, vertebral canal shape, and vertebral body shape in Doberman Pinschers with and without disk-associated cervical spondylomyelopathy (DACSM) and clinically normal English Foxhounds. Animals—Doberman Pinschers with (n = 18) and without (20) DACSM and clinically normal English Foxhounds (18). Procedures—All dogs underwent low-field MRI of the cervical vertebral column. From 5 specific measurements made at C3 through C7, 4 linear vertebral ratios were calculated and assessed for correlation: vertebral canal height-to-body height ratio (CBHR), vertebral canal height-to-body length ratio (CBLR), caudal canal height-to-cranial canal height ratio (CCHR), and vertebral body length-to-height ratio (BLHR). The CBHR and CBLR described vertebral canal height, CCHR described vertebral canal shape, and BLHR described vertebral body shape. A midvertebral canal-occupying ratio (mVCOR) for the spinal cord was calculated at C5. Results—Compared with both groups of unaffected dogs, CBHR, CBLR, and BLHR for Doberman Pinschers with DACSM were significantly smaller. The C7 CCHR was significantly larger in DACSM-affected Doberman Pinschers, compared with clinically normal English Foxhounds. Ratios did not differ significantly between unaffected Doberman Pinschers and clinically normal English Foxhounds. Correlation coefficients between CBHR, CBLR, and mVCOR were low and not significant. Conclusions and Clinical Relevance—Doberman Pinschers with DACSM had significantly smaller vertebral canal heights and more square-shaped vertebral bodies, compared with unaffected Doberman Pinschers, combined with a funnel-shaped vertebral canal at C7. Breed-specific differences were not evident. Linear MRI vertebral canal-to-body ratios do not appear to predict relative vertebral canal stenosis.

Objective-To investigate shedding of chlamydiae from conjunctiva and genital tracts of cats without clinical signs of conjunctivitis or other infectious disease in relation to their titers of serum antibodies against chlamydiae and to serum amyloid A (SAA) and serum alpha1-acid glycoprotein (AGP) concentrations. Animals-62 healthy cats. Procedures-Serum from each cat was analyzed for antibodies against chlamydiae and for SAA and AGP concentrations. Swab samples from the conjunctival sac and genital tract were analyzed with a real-time PCR assay for Chlamydiaceae. Results-4 of 8 of cats with high antibody titers (ie, 1,600) shed chlamydiae, but only from the conjunctiva. Chlamydiae could not be detected in samples from cats with lower antibody titers nor from any genital tract samples. In cats with antibody titers of 1,600, mean +/- SD SAA concentration was significantly higher when chlamydiae were detected in conjunctival swab samples (3.9 +/- 1.0 mg/L) than when no chlamydiae were detected (1.4 +/- 1.0 mg/L). However, SAA concentration was greater than the limit for an acute-phase response in only one of those cats. There was no significant difference in serum AGP concentrations between cats with high titers that were or were not shedding chlamydiae. Nine of 30 (30%) cats (5 with and 4 without detectable serum antibodies against chlamydiae) that had been mated developed reproductive disorders. Conclusions and Clinical Relevance-Clinically normal cats with high chlamydiae-specific antibody titers can shed and thus transmit chlamydiae. Venereal spread from cats without clinical signs of infection is likely not common.

Objective—To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa. Sample—Gastric mucosa from 6 mature mixed-breed dogs. Procedures—Sections of gastric mucosa were mounted in Ussing chambers, and carprofen (40 or 400μg/mL [CAR40 and CAR400, respectively]), meloxicam (8 or 80μg/mL [MEL8 and MEL80, respectively]), or no drug (controls) was added to the bathing solution. For all sections, conductance was calculated every 15 minutes for 240 minutes and flux of mannitol was calculated for 3 consecutive 1-hour periods; histologic examination was performed after the experiment. The area under the conductance-time curve for each chamber was calculated. Values of conductance × time, flux of mannitol, and the frequency distribution of histologic findings were analyzed for treatment effects. Results—For CAR400- and MEL80-treated sections, conductance X time was significantly higher than that for control and MEL8-treated sections. The effect of CAR40 treatment was not different from that of any other treatment. Over the three 1-hour periods, mannitol flux increased significantly in MEL80-, CAR40-, and CAR400-treated sections but not in MEL8- treated or control sections. Major histologic changes including epithelial cell sloughing were limited to the CAR400-treated sections. Conclusions and Clinical Relevance—In the gastric mucosa of dogs, carprofen and meloxicam increased in vitro conductance and permeability to mannitol. At a concentration of 400 μg/mL, carprofen caused sloughing of epithelial cells. Carprofen and meloxicam appear to compromise gastric mucosal integrity and barrier function in dogs.

Objective—To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs. Animals—-1,551 dogs. Procedures—Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever–Greyhound crossbreeds. Results—The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage. Conclusions and Clinical Relevance—The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.

Objective—To evaluate effects of cyclosporine, dexamethasone, and the immunosuppressive agent human CTLA4-Ig on cytokine production by feline lymphocytes in vitro and to assess patterns of cytokine production for 5 immunosuppressed renal transplant recipient cats. Animals—21 clinically normal cats and 5 immunosupressed renal transplant recipient cats. Procedures--Peripheral blood mononuclear cells were isolated from clinically normal cats and stimulated with concanavalin A (Con A; 10 μg/mL) alone or Con A with cyclosporine (0.05 μg/mL), dexamethasone (1 × 10−7M), a combination of cyclosporine-dexamethasone, or human CTLA4-Ig (10 g/mL). Cells from transplant recipients were stimulated with Con A alone. An ELISA was performed to measure production of interferon (IFN)-γ, granulocyte macrophage–colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, and IL-10. Proliferation of CD4+ and CD8+T cells from immunosuppressed cats were also evaluated. Pairwise comparisons were performed via a Wilcoxon signed rank test or Wilcoxon rank sum test. Results—Cyclosporine, dexamethasone, cyclosporine-dexamethasone combination, and CTLA4-Ig caused a significant decrease in IL-2, IFN-γ, and GM-CSF production. Cyclosporine and cyclosporine-dexamethasone, but not human CTLA4-Ig, caused a significant decrease in IL-10 production. High basal concentrations of IL-2 and IL-10 were identified in transplant recipients, and IL-10 was significantly increased in stimulated cultures. In immunosuppressed cats, there was a decrease in frequency of responders and proliferative capacity of CD4+ and CD8+T cells. Conclusions and Clinical Relevance—CTLA4-Ig successfully inhibited proinflammatory cytokines while sparing cytokines critical for allograft tolerance. These data may be useful for developing better strategies to prevent rejection while sparing other immune functions

Objective—To determine ocular tissue drug concentrations after topical ocular administration of 0.3% ciprofloxacin and 0.5% moxifloxacin in ophthalmologically normal horses. Animals—24 ophthalmologically normal adult horses. Procedures—0.3% ciprofloxacin and 0.5% moxifloxacin solutions (0.1 mL) were applied to the ventral conjunctival fornix of 1 eye in each horse as follows: group 1 (n = 8) at 0, 2, 4, and 6 hours; group 2 (8) at 0, 2, 4, 6, and 10 hours; and group 3 (8) at 0, 2, 4, 6, 10, and 14 hours. Tears, cornea, and aqueous humor (AH) were collected at 8, 14, and 18 hours for groups 1, 2, and 3, respectively. Drug concentrations were determined via high-performance liquid chromatography. Results—Median (25th to 75th percentile) concentrations of ciprofloxacin for groups 1, 2, and 3 in tears (μg/mL) were 53.7 (25.5 to 88.8), 48.5 (19.7 to 74.7), and 24.4 (15.4 to 67.1), respectively; in corneal tissue (μg/g) were 0.95 (0.60 to 1.02), 0.37 (0.32 to 0.47), and 0.48 (0.34 to 0.95), respectively; and in AH were lower than the limit of quantification in all groups. Concentrations of moxifloxacin for groups 1, 2, and 3 in tears (μg/mL) were 188.7 (44.5 to 669.2), 107.4 (41.7 to 296.5), and 178.1 (70.1 to 400.6), respectively; in corneal tissue (μg/g) were 1.84 (1.44 to 2.11), 0.78 (0.55 to 0.98), and 0.77 (0.65 to 0.97), respectively; and in AH (μg/mL) were 0.06 (0.04 to 0.08), 0.03 (0.02 to 0.05), and 0.02 (0.01 to 0.04), respectively. Corneal moxifloxacin concentrations were significantly higher in group 1 than groups 2 and 3. Conclusions and Clinical Relevance—After topical ocular administration, fluoroquinolones can reach therapeutic concentrations in tears and corneal tissue of horses, even when there is an intact epithelium.

Objective-To determine the accuracy of pressure plate kinetic asymmetry indices (ASIs) for diagnosis of unilateral hind limb lameness in dogs and their correlation with visual gait assessment (VGA) scores. Animals-9 healthy dogs and 16 dogs with previously diagnosed unilateral rupture of the cranial cruciate ligament and concurrent unilateral hind limb lameness. Procedures-Dogs were walked over a pressure plate to determine paw contact area (PCA), peak vertical pressure (PVP), peak vertical force (PVF), and vertical impulse (VI) of both hind limbs. An ASI was calculated for each gait variable. Simultaneously, gait was assessed visually and scored by use of a numeric rating scale (0 to 10). The ASI of each variable was tested for its usefulness in discrimination between lame and nonlame dogs and for correlation with VGA scores. Results-Sensitivity and specificity of ASIs to discriminate between lame and nonlame dogs were excellent for PVF, VI, and PCA; these values were substantially lower for ASI of PVP. Cutoff values to discriminate between lame and nonlame dogs were determined by use of ASIs for PVF, VI, and PCA; however, this could not be done for ASI of PVP. Correlations between ASIs of PVF, VI, and PCA and VGA scores were higher than correlation between the ASIs of PVP and VGA scores. Conclusions and Clinical Relevance-Results indicated that ASIs of PVF and VI determined via analysis of pressure plate measurements were reliable indicators of clinical lameness in dogs, but the ASI of PVP was not. The ASI of PCA is an interesting new variable for assessment of limb loading symmetry.