Middle Carpal Joint Research Articles

Efficacy of intravenous administration of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses.

OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. ANIMALS 32 healthy 2- to 5-year-old horses. PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups. RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm.

Effect of Dose on Intra-Articular Amikacin Sulfate Concentrations Following Intravenous Regional Limb Perfusion in Horses.

To compare synovial concentrations of amikacin following intravenous regional limb perfusion (IVRLP) with two different doses, and to compare their ability to reach target concentrations for bacterial isolates from common orthopedic conditions. Randomized crossover experiment. Six adult horses. Horses received IVRLP with 2 and 3 g of amikacin in the cephalic vein of alternate limbs (20 minutes tourniquet application and ≥14 days washout period). Amikacin concentrations were quantified in synovial fluid collected from the middle carpal and metacarpophalangeal joints at 25 minutes, and 24, 36, and 48 hours after IVRLP. Minimum inhibitory concentrations (MIC) were determined from equine bacterial isolates and ability to reach target amikacin concentrations were compared. Overall, middle carpal joint amikacin concentrations were higher following IVRLP with 3 g amikacin compared to 2 g (P=.031), with significant differences at 25 minutes (P=.002) and 24 hours (P=.021). No differences were observed between doses in the metacarpophalangeal joint (P=.267). Target amikacin concentrations for Staphylococcus aureus and coagulase-negative staphylococci were achieved in middle carpal and metacarpophalangeal joints at 25 minutes with both dosages and for Escherichia coli and Actinobacillus spp. in the middle carpal joint at 25 minutes with 3 g. Target concentrations were not achieved for Enterococcus spp, Pseudomonas spp, or Streptococcus equi ssp. zooepidemicus. A 3 g amikacin dose is not justified in the majority of distal limb injuries, but should be reserved for isolates with an MIC higher than that achievable with a 2 g dose. Daily IVRLP may be necessary based on our results.

Carpal arthrodesis using a minimally invasive approach and locking compression plates: Three cases

SummaryThree horses with carpal instability due to comminuted second carpal bone fractures (Cases 1 and 3), fracture of the head of the second metacarpal bone (Case 1) or comminuted fractures of the fourth carpal bone, ulnar and intermediate carpal bones (Case 2) were treated by minimally invasive approach for partial (Cases 1 and 3) or pancarpal (Case 2) joint arthrodesis, using locking compression plates. The joint cartilage was removed by either an arthroscopic approach (middle carpal joint and antebrachiocarpal joint) or a percutaneous drilling technique (carpometacarpal joint). Two or 3 locking compression plates were contoured to the dorsolateral, dorsomedial and dorsoaxial aspects of the carpal joints using a custom‐made tunnelling tool and a minimally invasive tunnelling technique, and the screws were positioned through stab incisions. All cases recovered well, were lame free at the walk, were able to trot and gallop and could be used for leisure and pasture activities (partial carpal arthrodesis) and breeding (pancarpal arthrodesis). Post‐operative x‐rays showed progressive joint fusion after 12 months (Case 1), 5 months (Case 2) and 10 months (Case 3). Case 2 with a pancarpal arthrodesis showed a mechanical lameness at the walk due to the inability to flex the carpus. Carpal flexion after carpometacarpal and middle carpal arthrodesis in Case 1 was calculated to be 42.6° and 44° in Case 3.

Dorsal Arthroscopic Approach and Intra-Articular Anatomy of the Bovine Antebrachiocarpal and Middle Carpal Joints.

To determine arthroscopic approaches to the dorsal synovial compartments of the antebrachiocarpal and middle carpal joints in adult cattle, and to describe the arthroscopic intra-articular anatomy from each approach. Ex vivo study. Six fresh adult bovine cadavers. Two carpi were injected with latex and dissected to determine the ideal location for arthroscopic portals. Arthroscopy of the antebrachiocarpal and middle carpal joints of 10 carpi was then performed. The dorsolateral approach was made between the extensor carpi radialis and common digital extensor tendons. The dorsomedial approach was made medial to the extensor carpi radialis tendon, midway between the distal radius and proximal row of carpal bones (antebrachiocarpal joint) and midway between the two rows of carpal bones (middle carpal joint), with the joint in flexion. Arthroscopy of the antebrachiocarpal joint allowed visualization of the distal radius, proximal aspect of the radial, intermediate and ulnar carpal bones, and a palmar ligament located between the radius and the intermediate carpal bone. The approach to the middle carpal joint allowed visualization of the distal aspect of the radial, intermediate, and ulnar carpal bones, the proximal aspect of the fourth and fused second and third carpal bones and an interosseous ligament. The most lateral articular structures (lateral glenoid cavity of the distal radius, ulnar carpal and fourth carpal bones) were difficult to assess. Dorsal approaches to the antebrachiocarpal and middle carpal joints allowed visualization of most intra-articular dorsal structures in adult cattle.

MAGNETIC RESONANCE IMAGING SCORING OF AN EXPERIMENTAL MODEL OF POST-TRAUMATIC OSTEOARTHRITIS IN THE EQUINE CARPUS.

Magnetic resonance imaging (MRI) is the most sensitive imaging modality to detect the early changes of osteoarthritis. Currently, there is no quantifiable method to tract these pathological changes over time in the horse. The objective of this experimental study was to characterize the progression of MRI changes in an equine model of post-traumatic osteoarthritis using a semiquantitative scoring system for whole-organ evaluation of the middle carpal joint. On day 0, an osteochondral fragment was created in one middle carpal joint (OCI) and the contralateral joint (CON) was sham-operated in 10 horses. On day 14, study horses resumed exercise on a high-speed treadmill until the completion of the study (day 98). High-field MRI examinations were performed on days 0 (preosteochondral fragmentation), 14, and 98 and scored by three blinded observers using consensus agreement. Images were scored based on 15 independent articular features, and scores were compared between and within-groups. On days 14 and 98, OCI joints had significantly (P ≤ 0.05) higher whole-organ median scores (29.0 and 31.5, respectively), compared to CON joints (21.5 and 20.0, respectively). On day 14, OCI joints showed significant increases in high-signal bone lesion scores, and osteochondral fragment number and size. On day 98, high-signal bone lesion, low-signal bone lesion, osteophyte formation, cartilage signal abnormality, subchondral bone irregularity, joint effusion, and synovial thickening scores were significantly increased in OCI joints. Study results suggest that the MRI whole-organ scoring system reported here may be used to identify onset and progression of pathological changes following osteochondral injury.

Osteoarthritic sclerotic subchondral osteoblasts secreted elevated concentration of Fibulin-3 fragments in vitro

Osteoarthritic sclerotic subchondral osteoblasts secreted elevated concentration of Fibulin-3 fragments in vitro

Effect of Arthroscopic Lavage on Systemic and Synovial Fluid Serum Amyloid A in Healthy Horses.

To evaluate the effect of arthroscopic lavage on systemic serum amyloid A (SAA) and SAA, total protein, nucleated cell count, and percentage of neutrophils in synovial fluid in healthy horses. Prospective experimental study. Healthy adult horses (n = 6). Middle carpal joints were randomly assigned to 1 of 2 treatments: arthrocentesis (controls) or arthroscopic lavage, with 30 day washout period between treatments. Synovial fluid and blood samples were collected at 0, 24, 48, 72, 96, and 120 hours. Measurements included systemic and synovial fluid SAA, as well as total protein, nucleated cell count, and percentages of neutrophils in synovial fluid. Data were analyzed by median quantile regression and Wilcoxon signed-rank test and significance level set at P < .05. Systemic and synovial fluid SAA did not increase from baseline (except systemic SAA at 24 hours for both treatments) and were not significantly different between treatments. Total protein values were significantly increased after arthroscopic lavage (except at 96 hours) but not in controls at all time points. With both treatments, nucleated cell counts significantly increased from baseline values at all time points. Percentages of neutrophils were significantly increased after arthroscopic lavage at all time points, but only at 24 hours in controls. Total protein, nucleated cell count, and percentage of neutrophils in synovial fluid were significantly increased after arthroscopic lavage; however, synovial fluid SAA was not affected by this procedure. Further research is warranted to validate synovial fluid SAA as a monitoring tool during treatment of septic arthritis.

Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.

The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various times up to 28 days post drug administration. All samples were analyzed using liquid chromatography-Mass Spectrometry. Plasma data were analyzed using a population pharmacokinetic compartmental model. Maximum measured plasma isoflupredone concentrations were 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 h and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 h, respectively, for horses that had synovial fluid collected and for those that did not. The plasma beta half-life was 24.2 h. Isoflupredone concentrations were below the limit of detection in all horses by 48 h and 7 days in plasma and urine, respectively. Isoflupredone was detected in the right antebrachiocarpal and middle carpal joints for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively. Results of this study provide information that can be used to regulate the use of intra-articular isoflupredone in the horse.

Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self-limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model.

Improvement has been reported following intra-articular (i.a.) injection of mesenchymal stromal cells (MSCs) in several species. These observations have led to the use of i.a. MSCs in equine practice with little understanding of the mechanisms by which perceived improvement occurs. To evaluate the effect of i.a. allogeneic umbilical cord blood (CB-) derived MSCs using a lipopolysaccharide (LPS) induced synovitis model. We hypothesised that i.a. CB-MSCs would reduce the inflammatory response associated with LPS injection. Randomised, blinded experimental study. Feasibility studies evaluated i.a. LPS or CB-MSCs alone into the tarsocrural joint. In the principal study, middle carpal joint synovitis was induced bilaterally with LPS and then CB-MSCs were injected into one middle carpal joint. Lameness, routine synovial fluid analysis, and synovial fluid biomarkers were evaluated at 0, 8, 24, 48 and 72h. LPS injection alone resulted in transient lameness and signs of inflammation. In joints untreated with LPS, injection of 30 million CB-MSCs resulted in mild synovitis that resolved without treatment. Mild (grade 1-2) lameness in the CB-MSC-treated limb was observed in 2 horses and severe lameness (grade 4) in the 3rd, 24h post injection. Lameness did not correlate with synovitis induced by CB-MSC injection. Simultaneous injection of LPS and CB-MSCs resulted in significant reduction in synovial fluid total nucleated, neutrophil and mononuclear cell numbers compared with contralateral LPS-only joints. No difference was detected in other parameters associated with synovial fluid analysis or in synovial fluid biomarkers. The incidence of lameness was only different from baseline at 8h, where horses were lame in CB-MSC limbs. Allogeneic CB-MSCs reduced synovial fluid cell populations and stimulated mild self-limiting inflammation in the synovitis model. Continued evaluation of the effects of i.a. CB-MSC therapy on synovitis in horses is needed to evaluate anti- and proinflammatory properties of CB-MSCs. Immediate interests are dose, timing of treatment, and treatment frequency.

Comparison of subjective lameness evaluation, force platforms and an inertial-sensor system to identify mild lameness in an equine osteoarthritis model

When mild lameness exists, agreement between clinicians is often controversial due to its subjective nature. The goal of the study was to compare subjective and objective methods to identify the presence of mild lameness using an established model of osteoarthritis (OA) in which OA was induced by creating a unilateral carpal osteochondral fragment (OCF) in the middle carpal joint of 16 horses. Subjective lameness evaluations (blinded and unblinded), force platforms (FP), and an inertial-sensor system (ISS) were used to detect forelimb lameness at four time points. Limbs identified as lame by each method were compared as well as compared with the OCF limb at each time point. Spearman correlations were calculated between all outcome parameters.Independent of time, blinded subjective evaluation (54%) and the ISS (60%) identified a higher percentage of horses as lame in the OCF limb compared to FP (40%). Blinded subjective evaluation and the ISS agreed which forelimb was lame more often (50%) compared with blinded subjective evaluation and the FP (38%). Induction of mild lameness within the OCF limb was supported by an increase in the frequency of horses considered lame by both subjective evaluations the ISS and a decrease (3.6%) in mean (among all horses) peak vertical force from baseline to post OCF induction. The percentage of horses identified as lame in the OCF limb, independent of time, was highest with the ISS (60%) followed by blinded subjective evaluation (51%) and the FP (42%). It was concluded that the best agreement was between subjective evaluation and the inertial-sensor system.

Arthroscopic removal of discrete palmar carpal osteochondral fragments in horses: 25 cases (1999-2013).

To characterize discrete palmar carpal osteochondral fragmentation in horses and to document the effect of osteoarthritis and surgical removal of these fragments on functional outcome. Retrospective case series. 25 horses. Medical records and radiographic views were reviewed to identify horses that had radiographic evidence of palmar carpal fragmentation, which was subsequently treated by arthroscopic removal. Information collected included cause of fracture, initial and long-term clinical and radiographic findings, and functional outcome. Palmar carpal fragmentation of 30 carpal bones was identified in 25 unilaterally affected horses. A known traumatic event was reported to cause the fragmentation in 17 of the 25 (68%) horses. Of the 25 horses, 17 (68%) had fragmentation involving the antebrachiocarpal joint, 7 (28%) had fragmentation involving the middle carpal joint, and 1 (4%) had fragmentation involving the carpometacarpal joint. The proximal aspect of the radial carpal bone was the most commonly affected site (12/30 fragments), followed by the accessory carpal bone (6/30). Of the 25 horses, 19 (76%) were not lame (sound) after surgery and returned to their intended use, 4 (16%) were considered pasture sound, and 2 were euthanized (because of severe postoperative osteoarthritis or long bone fracture during recovery from anesthesia). Eight of the 14 horses with preoperative evidence of osteoarthritis returned to function after surgery. Twelve of 17 horses with antebrachiocarpal joint fragments and 6 of 7 horses with middle carpal joint fragments returned to their previous use. Results indicated that the prognosis for horses after arthroscopic removal of palmar carpal osteochondral fragments is good. Early intervention, before the development of osteoarthritis, is recommended.

Concurrent proximal suspensory desmopathy and injury of the proximal aspect of the accessory ligament of the deep digital flexor tendon in forelimbs or hindlimbs in 19 horses

SummaryClinical features of proximal suspensory desmopathy (PSD) and concurrent injury of the proximal aspect of the accessory ligament of the deep digital flexor tendon (ALDDFT) have not been documented. The objectives were to describe clinical signs and diagnosis. This was a retrospective study. Patient details, lame limb(s), response to diagnostic analgesia, and radiographic and ultrasonographic findings were recorded. PSD and injury of the proximal aspect of the ALDDFT were identified in 19 horses, 14 with forelimb lameness (unilateral 5, bilateral 9) and 5 with hindlimb lameness (unilateral 2, bilateral 3). Localising clinical signs were seen in 7/31 lame limbs (subtle thickening in the region of the ALDDFT [n = 3], pain on palpation of the body of the suspensory ligament (SL) [n = 6], heat in the proximal metacarpal or metatarsal region [n = 2]). Forelimb lameness was abolished by perineural analgesia of the palmar metacarpal (subcarpal) nerves in 17/23 limbs. In the remaining limbs intra‐articular analgesia of the middle carpal joint (n = 2) or an ulnar nerve block (n = 4) were required to eliminate the lameness. Hindlimb lameness was abolished by perineural analgesia of the deep branch of the lateral plantar nerve (n = 2) or local infiltration of the proximal plantar aspect of the metatarsus (n = 3); a tibial nerve block resolved lameness in the remaining 3 limbs. Lesions of the SL and of the ALDDFT were characterised ultrasonographically by enlargement, heterogeneous echogenicity and loss of long linear echoes in longitudinal images. In 3 horses adhesions between the ALDDFT and the SL were identified post mortem. Close apposition of these structures seen ultrasonographically may indicate adhesion formation. It was concluded that the clinical features of PSD and concurrent injury of the ALDDFT are similar to those for PSD alone, highlighting the need for comprehensive and systematic ultrasonographic assessment.

Humoral and cell-mediated immune response, and growth factor synthesis after direct intraarticular injection of rAAV2-IGF-I and rAAV5-IGF-I in the equine middle carpal joint.

Intraarticular (IA) administration of viral vectors expressing a therapeutic transgene is an attractive treatment modality for osteoarthritis (OA) as the joint can be treated as a contained unit. Humoral and cell-mediated immune responses in vivo can limit vector effectiveness. Transduction of articular tissues has been investigated; however, the immune response to IA vectors remains largely unknown. We hypothesized that IA rAAV2 and rAAV5 overexpressing insulin-like growth factor-I (IGF-I) would result in long-term IGF-I formation but would also induce neutralizing antibodies (NAb) and anti-capsid effector T cells. Twelve healthy horses were assigned to treatment (rAAV2 or rAAV5) or control (saline) groups. Middle carpal joints were injected with 5×10(11) vector genomes/joint. Synovial fluid was analyzed for changes in composition, NAb titers, immunoglobulin isotypes, proinflammatory cytokines, and IGF-I. Serum was analyzed for antibody titers and cytokines. A T cell restimulation assay was used to assess T cell responses. Injection of rAAV2- or rAAV5-IGF-I did not induce greater inflammation compared with saline. Synovial fluid IGF-I was significantly increased in both rAAV2- and rAAV5-IGF-I joints by day 14 and remained elevated until day 56; however, rAAV5 achieved the highest concentrations. A capsid-specific T cell response was not noted although all virus-treated horses had increased NAbs in serum and synovial fluid after treatment. Taken together, our data show that IA injection of rAAV2- or rAAV5-IGF-I does not incite a clinically detectable inflammatory or cell-mediated immune response and that IA gene therapy using minimally immunogenic vectors represents a clinically relevant tool for treating articular disorders including OA.

Changes in Synovial Fluid Inflammatory Mediators and Cartilage Biomarkers After Experimental Acute Equine Synovitis

Abstract The purpose of the study was to define transient changes in the concentration of inflammatory biomarkers and cartilage biomarkers in the synovial fluid of joints following experimentally induced acute equine synovitis. Acute synovitis was induced in eight skeletally mature mares by a sterile intra-articular injection of 1 mL of phosphate-buffered saline (PBS) containing 0.5 ng of lipopolysaccharide (LPS). The solution was injected into the right middle carpal joint. One mL of sterile PBS was injected into the left control joint. Synovial fluid was obtained at the baseline level and at 8, 24, and 168 h after injection. The levels of inflammatory biomarkers-prostaglandin E2 (PGE2), interleukin 1β (IL-1β), and tumour necrosis factor-α (TNF-α), and cartilage turnover biomarkers-collagenase-cleavage neoepitope of type II collagen (C2C) and C-terminal crosslinked telopeptide type II collagen (CTX-II) were detected with proper assays. Single injections of LPS raised the number of synovial white blood cells and concentrations of total protein, PGE2, IL-1β, TNF-α, C2C, and CTX-II. PGE2 and IL-1β rose sharply at 8 h, while TNF-α increased steadily through 8 h and 24 h, at that point; these three factors returned to the baseline level by 168 h. The time course of C2C and CTX-II concentrations peaked sharply at 24 h, and continued to be significantly elevated over the baseline level even at 168 h. Injections of LPS into the joints led to a temporal inflammatory response, which in turn increased local release of inflammatory biomarkers and significantly altered the concentrations of cartilage markers in the synovial fluid.

Repetitive stress-related injury of the proximal metacarpus in a seven-year old Thoroughbred racehorse with emphasis on diagnostic analgesia of the proximopalmar metacarpus.

SummaryThis report describes the diagnosis and management of repetitive stress-related injury (RSRI) of the proximal metacarpus in a seven-year old Thoroughbred racehorse. Intra-articular analgesia of the middle carpal joint (MCJ) as well as perineural analgesia of the lateral palmar nerve (LPN) abolished lameness and a diagnosis of RSRI of the proximopalmar metacarpus was made after nuclear scintigraphic examination. Given the response to intra-articular analgesia, the authors undertook a cadaver study in order to better describe the relationship between the medial and lateral palmar pouches of carpo-metacarpal joint (CMCJ), the LPN and the deep branch of the lateral palmar nerve (DBLPaN).

Ex vivo evaluation of carpal flexion after partial carpal arthrodesis in horses.

To determine degrees of flexion after arthrodesis of the antebrachiocarpal (ABC) joint, middle carpal (MC), and carpometacarpal (CMC) joints combined (MC/CMC), and carpometacarpal (CMC) joint alone. Ex vivo study. Forelimbs (n = 9) from 2- to 10-year-old Quarter Horses (5), Thoroughbred (2), and American Paint Horse (2). Using 2 locking compression plates, 3 partial carpal arthrodesis techniques were performed. Cables and deadweights were connected to limbs and each angle of flexion determined 3 times using a protractor and then averaged. Control measurements were obtained before and after arthrodesis, the techniques randomized with Latin square design. Descriptive data were analyzed with Levene's test, Q-Q plots, ANOVA, and Bonferroni test. Mean ± SD carpal flexion results were: controls 150° ± 8°, CMC arthrodesis 149° ± 9°, MC/CMC arthrodesis 43° ± 7.6°, and ABC arthrodesis 25° ± 6.3°. There was no significant reduction in flexion after a CMC arthrodesis compared with controls (P = .21), but there was after ABC (P < .001) and MC/CMC arthrodesis (P < .001), with the ABC arthrodesis significantly reduced compared with an MC/CMC arthrodesis (P < .001). Whereas CMC arthrodesis does not affect carpal flexion, CMC/MC and ABC arthrodesis markedly reduce the degree of carpal flexion.

Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses-a preliminary investigation.

To determine effects of intraarticularly administered tiludronate on articular cartilage in vivo, eight healthy horses were injected once with tiludronate (low dose tiludronate [LDT] 0.017 mg, n = 4; high dose tiludronate [HDT] 50 mg, n = 4) into one middle carpal joint and with saline into the contralateral joint. Arthrocentesis of both middle carpal joints was performed pre-treatment, and 10 min, 24 h, 48 h, 7 and 14 days after treatment. Synovial nucleated cell counts and total solids, tiludronate, sulfated glycosaminoglycan (sGAG), chondroitin sulfate 846 epitope (CS-846, a measure of aggrecan synthesis), and collagen type II cleavage neoepitope (C2C) concentrations were determined. Histologic analysis of joint tissues and sGAG quantitation in cartilage was performed at 14 days in HDT horses. Data were analyzed by repeated measures non-parametric ANOVA and Wilcoxon signed-rank test. High dose tiludronate administration produced synovial fluid tiludronate concentrations of 2,677,500 ng/mL, exceeding concentrations that were safe for cartilage in vitro, and LDT administration produced synovial fluid concentrations of 1,353 ng/mL, remaining below concentrations considered potentially detrimental to cartilage. With HDT, synovial fluid total solids concentration was higher at 24 h and 7 days and sGAG concentration was higher at 48 h, compared to control joints. Synovial fluid CS-846 concentration was increased over pre-treatment values in HDT control but not in HDT treated joints at 24 and 48 h. All joints (HDT and LDT control and treated) showed a temporary decrease in synovial fluid C2C concentration, compared to pre-treatment values. Histologic features of articular cartilage and synovial membrane did not differ between HDT treated and control joints. High dose tiludronate treatment caused a transient increase in synovial total solids and temporarily increased proteoglycan degradation in cartilage. Although clinical significance of these changes are questionable, as they did not result in articular cartilage damage, further investigation of the safety of intraarticular HDT in a larger number of horses is warranted.

In vivo effects of phenylbutazone on inflammation and cartilage-derived biomarkers in equine joints with acute synovitis

Although phenylbutazone (PBZ) is commonly used in equine orthopaedic practice, little is known about its in vivo effects on joint inflammation and cartilage turnover. This study investigates the effects of PBZ on inflammatory parameters, matrix metalloproteinase (MMP) activity and cartilage biomarkers in equine joints with acute synovitis. In a two-period cross-over study, transient synovitis was induced at T = 0 h in the middle carpal joint of seven ponies by lipopolysaccharide (LPS) injection. Ponies received PBZ (2 mg/kg PO twice daily) or placebo for 1 week, starting at T = 2 h. Arthroscopic assessment of the middle carpal joint was performed at T = −504, 48 and 672 h. Synovial fluid (SF) was sampled at T = −504, 0, 8, 24, 48, 168, 336 and 672 h and analysed for leukocytes and total protein, substance P, general MMP activity, glycosaminoglycans (GAG), collagen II cleavage marker C2C and synthesis marker CPII. Markers in PBZ- vs. placebo-treated joints were compared over time using a linear mixed model.LPS injection caused marked transient synovitis without visible cartilage changes. Substance P and general MMP activity were not significantly reduced by PBZ treatment, nor were SF GAG or C2C concentrations at any time point. Concentration of CPII was significantly lower at T = 24 and 168 h in PBZ treated joints compared to placebo. Although PBZ is clinically effective in treating acute synovitis, it does not limit inflammation-induced cartilage catabolism and may transiently reduce collagen anabolism as evidenced by SF markers.

Accumulation of Amikacin in Synovial Fluid After Regional Limb Perfusion of Amikacin Sulfate Alone and in Combination With Ticarcillin/Clavulanate in Horses

To determine the effect of regional limb perfusion (RLP) with amikacin sulfate alone and in combination with ticarcillin/clavulanate on synovial fluid concentration and antimicrobial activity of amikacin. Experimental study. RLP with amikacin alone (A; 2.5 g) or amikacin and ticarcillin/clavulanate (AT; 2.5 g amikacin, 7 g ticarcillin/clavulanate) was performed with a tourniquet placed at mid-antebrachium in standing, sedated horses. Perfusate blood was collected immediately after injection and again before tourniquet release. Blood from the jugular vein was collected before tourniquet release. Synovial fluid from the middle carpal joint was collected 0, 30, and 60 minutes after tourniquet release. Amikacin concentration and antimicrobial activity of synovial fluid against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were determined. There was significantly lower amikacin concentration in the middle carpal joint synovial fluid of group AT compared with group A at 30 minutes (AT = median 4.4 µg/mL, IQR 3.0-11.2 µg/mL; A = 17.5 µg/mL, 6.6-80.1 µg/mL) and 60 minutes (AT = median 4.6 µg/mL, IQR 3.1-8.1 µg/mL; A = 15.0 µg/mL, 6.7-61.7 µg/mL) after tourniquet release. Zones of inhibition for ticarcillin-resistant Klebsiella pneumoniae from group AT were significantly smaller than group A from synovial fluid at 30 and 60 minutes after tourniquet release and in the perfusate serum before tourniquet release. The combination of amikacin with ticarcillin/clavulanate during RLP resulted in significantly lower amikacin synovial concentration and antimicrobial activity on amikacin susceptible and ticarcillin resistant cultures compared with amikacin alone.

Carbomer Viscosupplementation in the Equine Middle Carpal Joint

Joint visco supplementation is widely used in the sport horse industry, commonly utilizing hyaluronan. Similar to hyaluronan, the carbomer molecule has bioadhesive and viscoelastic properties, and has been 15 studied for use in human medicine. Carbomers are generally inert biologically, non-irritating, and have been used in humans as injectable depots for time-release medications. Our objective was to describe the outcome of intra-articular viscosupplementation with carbomer in four horses. Four healthy adult mares participated in this study. Baseline lameness examinations, aseptic arthrocenteses and synovial fluid analyses were performed. Three mL of 3% carbomer was then 20 injected into each left middle carpal joint. Lameness evaluations were repeated daily for each horse for ten days post-injection or until the time of euthanasia. At euthanasia, synovial fluid analyses were repeated on the left middle carpal joint. Samples of synovium from the left middle carpal joints were submitted for histopathology. Articular cartilage of the third carpal bone including subchondral bone was submitted for histology and confocal microscopy. 25 Carbomer viscosupplementation of the middle carpal joint caused severe lameness in 3 /4 mares. The fourth mare developed moderate lameness after injection. Confocal microscopy was negative for cartilaginous defects. Histology of all treated samples revealed varying degrees of small cell inflammatory infiltrate into the subsynovia. With no abnormal findings in samples of cartilage or subchondral bone, lameness is attributable to 30 severe synovitis, which is consistent with histologic findings of synovium in all cases. The current formulation of carbomer is therefore not suitable for intra-articular viscosupplementation in horses.