Objective: To determine mechanical properties of various prosthetic materials secured to cadaveric canine femurs via various methods and to compare results with those for isolated loops of prosthetic material. Sample: 80 femurs obtained from cadavers of skeletally mature large-breed dogs. Procedures: 10 femoral constructs in each of 8 groups (single circumfabellar loop of polyethylene cord, double loop of polyethylene tape secured via a bone anchor [BAPT], single or double circumfabellar loops of nylon leader material [CNL] or polyethylene tape [CPT], or single or double loops of polyethylene tape secured via a toggle placed through a bone tunnel [BTPT]) and 10 isolated loops of prosthetic material in each corresponding configuration were tested. Stress relaxation, creep, elongation, load at 3 mm of displacement, stiffness, and peak load at failure were determined. Results: 5 single CNL constructs failed before completion of testing. Double CNL and single circumfabellar polyethylene cord constructs had the lowest loads at 3 mm of displacement. Single and double CPT constructs had the highest stiffness. Double BTPT and CPT constructs had the highest peak loads at failure. Double BTPT, double CPT, and BAPT constructs were mechanically superior on the basis of lower creep and stress relaxation and higher stiffness and load at 3 mm of displacement versus other constructs. Stiffness of femoral constructs was 28% to 69% that of corresponding isolated prosthetic loops. Conclusions and Clinical Relevance: Double BTPT, double CPT, and BAPT constructs were mechanically superior to other constucts. Mechanical properties and methods of anchorage and securing of free ends of prostheses contributed to mechanical properties of constructs.

Objective: To determine concentration-dependent effects of tiludronate on cartilage explants incubated with or without recombinant equine interleukin-1β (rEq IL-1). Sample: Articular cartilage explants from the femorotibial joints of 3 young adult horses. Procedures: Cartilage explants were incubated with 1 of 6 concentrations (0, 0.19, 1.9, 19, 190, or 1,900 mg/L) of tiludronate and with or without rEq IL-1 (0.01 ng/mL) for 96 hours. Prostaglandin E2 (PGE2) concentrations in culture medium and explant digests were analyzed via PGE2 enzyme immunoassay. Sulfated glycosaminoglycan (sGAG) concentrations in culture medium were quantified via 1,9-dimethylmethylene blue assay. Chondrocyte apoptosis in paraffin embedded explant sections was measured via terminal deoxynucleotidyl transferase-mediated dUTP nick end–labeling assay. Relative gene expression of matrix metalloproteinases (MMPs), interleukin (IL)-6, and IL-8 was determined via the comparative cycle threshold method. Results: rEq IL-1 increased PGE2 concentration, sGAG release from explants, chondrocyte apoptosis, and MMP gene expression. Lower tiludronate concentrations reduced rEq IL-1–induced sGAG release and chondrocyte apoptosis, whereas the higher tiludronate concentrations increased sGAG release and chondrocyte apoptosis. At the highest tiludronate concentration evaluated, IL-8 gene expression was increased independent of whether rEq IL-1 was present. Conclusions and Clinical Relevance: Tiludronate had biphasic concentration-dependent effects on cartilage explants that were independent of PGE2 secretion or MMP gene expression. Low tiludronate concentrations had some chondroprotective effects, whereas high tiludronate concentrations were detrimental to equine articular cartilage. Administration of tiludronate intra-articularly to horses may be detrimental, dependent on the dose used. In vivo studies are needed before intra-articular tiludronate administration to horses can be recommended.

Objective: To assess joint kinematics in dogs with osteoarthritis of the hip joints during walking up an incline or down a decline and over low obstacles and to compare findings with data for nonlame dogs. Animals: 10 dogs with osteoarthritis of the hip joints (mean ± SD age, 6.95 ± 3.17 years; mean body weight, 34.33 ± 13.58 kg) and 8 nonlame dogs (3.4 ± 2.0 years; 23.6 ± 4.6 kg). Procedures: Reflective markers located on the limbs and high-speed cameras were used to record joint kinematics during walking up an incline or down a decline and over low obstacles. Maximal flexion, extension, and range of motion of the hip joints were calculated. Results: Osteoarthritis of the hip joints reduced extension of both hip joints and flexion of the contralateral hind limb, compared with flexion of the lame hind limb, during walking down a decline. Walking up an incline resulted in decreased extension of the stifle joint in both hind limbs of osteoarthritic dogs; extension was significantly decreased for the lame hind limb. During walking over low obstacles, maximal flexion of the stifle joint was increased significantly for the contralateral hind limb. Maximal flexion was increased in both tarsal joints. Conclusions and Clinical Relevance: Osteoarthritis of the hip joints led to complex changes in the gait of dogs, which involved more joints than the affected hip joint alone. Each exercise had specific effects on joint kinematics that must be considered when planning a rehabilitation program.

Objective: To determine the influence of intensified training and subsequent reduced training on glucose metabolism rate and peripheral insulin sensitivity in horses and identify potential markers indicative of early overtraining. Animals: 12 Standardbred geldings. Procedures: Horses underwent 4 phases of treadmill-based training. In phase 1, horses were habituated to the treadmill. In phase 2, endurance training was alternated with high-intensity exercise training. In phase 3, horses were divided into control and intensified training groups. In the intensified training group, training intensity, duration, and frequency were further increased via a protocol to induce overtraining; in the control group, these factors remained unaltered. In phase 4, training intensity was reduced. Standardized exercise tests were performed after each phase and hyperinsulinemic euglycemic clamp (HEC) tests were performed after phases 2, 3, and 4. Results: 10 of 12 horses completed the study. Dissociation between mean glucose metabolism rate and mean glucose metabolism rate-to-plasma insulin concentration ratio (M:I) was evident in the intensified training group during steady state of HEC testing after phases 3 and 4. After phase 4, mean glucose metabolism rate was significantly decreased (from 31.1 ± 6.8 μmol/kg/min to 18.1 ± 3.4 μmol/kg/min), as was M:I (from 1.05 ± 0.31 to 0.62 ± 0.17) during steady state in the intensified training group, compared with phase 3 values for the same horses. Conclusions and Clinical Relevance: Dissociation between the glucose metabolism rate and M:I in horses that underwent intensified training may reflect non-insulin–dependent increases in glucose metabolism.

Objective: To characterize acute inflammatory and hemostatic surgical stress responses following castration in cats and to evaluate whether the addition of local anesthesia to the anesthetic protocol attenuates these responses. Animals: 39 male cats. Procedures: Cats undergoing castration were randomly assigned to 2 groups: both groups underwent surgery with general anesthesia, and 1 group additionally received a local anesthetic (lidocaine [2.0 mg/kg in total, divided intratesticularly and SC]) prior to incision. Blood samples were collected after anesthetic induction (baseline) and 1, 5, and 24 hours later. Thromboelastography and coagulation variables (activated partial thromboplastin time [aPTT] and prothrombin time [PT]) were analyzed; fibrinolysis was assessed with plasma D-dimer concentrations. The acute-phase response was evaluated via measurement of plasma fibrinogen and serum amyloid A (last time point, 28 hours) concentrations. Hematologic variables were analyzed at baseline and 1, 5, and 24 hours later. Results: Evidence of hemostatic and inflammatory activation after surgery was detected in both groups. Maximum amplitude and G (global clot strength) were significantly increased at 24 hours, and significant, but not clinically relevant, decreases were detected in aPTT at 5 and 24 hours and in PT at 24 hours, compared with baseline values. Serum amyloid A concentrations were significantly higher at 24 and 28 hours than at baseline, and plasma fibrinogen concentration was significantly increased at 24 hours; WBC and RBC counts and Hct were significantly increased at multiple time points. No differences between groups were detected for any variables. Conclusions and Clinical Relevance: Castration appeared to induce hypercoagulability and an acute-phase inflammatory response in cats. Local anesthesia with lidocaine did not attenuate this response.

Objective: To compare the cardiorespiratory, gastrointestinal, analgesic, and behavioral effects between IV and IM administration of morphine in conscious horses with no signs of pain. Animals: 6 healthy adult horses. Procedures: Horses received saline (0.9% NaCl) solution (IM or IV) or morphine sulfate (0.05 and 0.1 mg/kg, IM or IV) in a randomized, masked crossover study design. The following variables were measured before and for 360 minutes after drug administration: heart and respiratory rates; systolic, diastolic, and mean arterial blood pressures; rectal temperature; arterial pH and blood gas variables; intestinal motility; and response to thermal and electrical noxious stimuli. Adverse effects and horse behavior were also recorded. Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were measured via liquid chromatography–mass spectrometry. Results: No significant differences in any variable were evident after saline solution administration. Intravenous and IM administration of morphine resulted in minimal and short-term cardiorespiratory, intestinal motility, and behavioral changes. A decrease in gastrointestinal motility was detected 1 to 2 hours after IM administration of morphine at doses of 0.05 and 0.1 mg/kg and after IV administration of morphine at a dose of 0.1 mg/kg. Morphine administration yielded no change in any horse's response to noxious stimuli. Both morphine-3-glucuronide and morphine-6-glucuronide were detected in plasma after IV and IM administration of morphine. Conclusions and Clinical Relevance: Clinically relevant doses of morphine sulfate yielded minimal and short-term behavioral and intestinal motility effects in healthy horses with no signs of pain. Neither dose of morphine affected their response to a noxious stimulus.

Objective: To evaluate the precision and accuracy of assessing bone mineral density (BMD) by use of mean gray value (MGV) on digitalized and digital images of conventional and digital radiographs, respectively, of ex vivo bovine and equine bone specimens in relation to the gold-standard technique of dual-energy x-ray absorptiometry (DEXA). Sample: Left and right metatarsal bones from 11 beef cattle and right femurs from 2 horses. Procedures: Bovine specimens were imaged by use of conventional radiography, whereas equine specimens were imaged by use of computed radiography (digital radiography). Each specimen was subsequently scanned by use of the same DEXA equipment. The BMD values resulting from each DEXA scan were paired with the MGVs obtained by use of software on the corresponding digitalized or digital radiographic image. Results: The MGV analysis of digitalized and digital x-ray images was a precise (coefficient of variation, 0.1 and 0.09, respectively) and highly accurate method for assessing BMD, compared with DEXA (correlation coefficient, 0.910 and 0.937 for conventional and digital radiography, respectively). Conclusions and Clinical Relevance: The high correlation between MGV and BMD indicated that MGV analysis may be a reliable alternative to DEXA in assessing radiographic bone density. This may provide a new, inexpensive, and readily available estimate of BMD.

This study examined known or possible virulence-associated genes in type A Clostridium perfringens from cases of both bovine clostridial abomasitis (BCA) and jejunal hemorrhage syndrome (JHS) and compared these to isolates from calves that were healthy or had undifferentiated diarrheal illness. A real-time polymerase chain reaction (PCR) assay was used to genotype the 218 C. perfringens isolates. Isolates were sourced from healthy and diarrheic young and mature cattle (n = 191), from calves with confirmed or suspected BCA (n = 22), and from mature cattle with JHS (n = 5). Of 216 isolates (96%), 208 were positive for the cpa gene and 13% (29/218) were positive for atypical cpb2. Three of 8 (37.5%) confirmed BCA isolates, 2 of 13 (15.4%) suspected BCA isolates, and no JHS isolates tested positive for atypical cpb2. As all isolates were negative for cpb, cpb2, cpe, etx, netB, and tpeL, the results of the present study do not support a role for these genes in BCA or JHS. A subset of unique genes identified in 1 bovine clostridial abomasitis isolate (F262), for which a genome sequence is available, was searched for in 8 BCA isolates by PCR. None of the 10 genes was consistently present in all or even in a majority of BCA isolates. Many of these genes were also variably and inconsistently present in type A isolates from calves that did not have BCA. Although a virulence signature to aid in the diagnosis of BCA caused by C. perfringens type A was not identified, further work may discover a gene or group of genes that would constitute such a signature.

The effects of 2 different continuous rate infusions (CRIs) of medetomidine over an 8-hour period on sedation score, selected cardiopulmonary parameters, and serum levels of medetomidine were evaluated in 6 healthy, conscious dogs using a crossover study design. The treatment groups were: CONTROL = saline bolus followed by saline CRI; MED1 = 2 μg/kg body weight (BW) medetomidine loading dose followed by 1 μg/kg BW per hour CRI; and MED2 = 4 μg/kg BW medetomidine loading dose followed by 2 μg/kg BW per hour CRI. Sedation score (SS), heart rate (HR), respiratory rate (RR), temperature (TEMP), systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP), arterial and mixed venous blood gas analyses, lactate, and plasma levels of medetomidine were evaluated at baseline, at various intervals during the infusion, and 2 h after terminating the infusion. Statistical analysis involved a repeated measures linear model. Both infusion rates of medetomidine-induced dose-dependent increases in SS and dose-dependent decreases in HR, SAP, MAP, and DAP were measured. Respiratory rate (RR), TEMP, central venous pH, central venous oxygen tension, and oxygen extraction ratio also decreased significantly in the MED2 group at certain time points. Arterial oxygen and carbon dioxide tensions were not significantly affected by either infusion rate. In healthy dogs, both infusion rates of medetomidine-induced clinically relevant sedative effects, accompanied by typical alpha2 agonist-induced hemodynamic effects, which plateaued during the infusion and subsequently returned to baseline. While additional studies in unhealthy animals are required, the results presented here suggest that medetomidine infusions at the doses studied may be useful in canine patients requiring sedation for extended periods.

Objective: To determine whether incubation of cruciate ligament cells with acetylsalicylic acid, carprofen, meloxicam, or robenacoxib provides protection against apoptosis induced by sodium nitroprusside (SNP). Sample: Explants of cranial (CCL) and caudal (CaCL) cruciate ligaments from eight 1-day-old Beagles. Procedures: Primary cultures of CCL and CaCL cells were created via enzymatic dissociation of cruciate explants. Purified cell cultures were incubated for 2 hours without (controls) or with 1 of 3 concentrations of 1 of 4 NSAIDs (10, 100, or 200 μg of acetylsalicylic acid/mL; 0.1, 1, or 10 μg of carprofen/mL; 0.1, 1, or 10 μg of meloxicam/mL; or 0.1, 1, or 10 μg of robenacoxib/mL) and subsequently incubated for 18 hours with 1 of 3 concentrations of SNP in an attempt to induce mild, moderate, or severe cytotoxic effects. Cell viability and apoptosis were analyzed via a cell proliferation assay and flow cytometry, respectively. Prostaglandin E2 concentrations were measured via an ELISA. Results: Cytoprotective effects of NSAIDs were dependent on the extent of SNP-induced apoptosis and were greatest in CCL and CaCL cell cultures with moderate SNP-induced cytotoxic effects. Preincubation with an NSAID improved cell viability by 15% to 45% when CCL and CaCL cells were subsequently incubated with SNP. Carprofen (10 μg/mL) had the greatest cytoprotective effects for CCL and CaCL cells. Incubation with NSAIDs resulted in a nonsignificant decrease in PGE2 production from SNP-damaged cells. Conclusions and Clinical Relevance: Results indicated that carprofen, meloxicam, and robenacoxib may reduce apoptosis in cells originating from canine cruciate ligaments.