Pharmacokinetics of ketoprofen in healthy horses and horses with acute synovitis

The pharmacokinetlc properties of a single intravenous dose of ketoprofen (2.2 mg/kg) in plasma and synovial fluid were compared in four healthy animals and four horses with experimentally induced acute synovitis. Synovitis was induced by the injection of a 1% solution of sterile carrageenan into the left intercarpal joint Ketoprofen was administered at the same time as carrageenan infection. The plasma disposition followed a biexponential equation or a two-compartment model in most horses. The plasma harmonic mean half-life in healthy horses (0.88 h) was longer than in horses with synovitis (0.5 5 h). Synovial fluid concentrations of ketoprofen in healthy horses approximated those in plasma by 3 h post-dose. In horses with synovitis, synovial fluid concentrations approximated plasma concentrations by 1 h. Synovial fluid concentrations of ketoprofen in horses with synovitis were 6.5 times higher than those in healthy horses at 1 h. The area under the synovial fluid concentration curve for horses with synovitis was greater than in healthy horses. These data suggest that the inflamed joint serves as a site of sequestration for ketoprofen. Furthermore, these results indicate that plasma pharmacokinetics may be altered by inflammation in a peripheral compartment such as the joint     

Gentamicin concentrations in synovial fluid and joint tissues during intravenous administration or continuous intra-articular infusion of the tarsocrural joint of clinically normal horses

OBJECTIVE: To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses. ANIMALS: 18 horses with clinically normal tarsocrural joints. PROCEDURE: Horses were assigned to 3 groups (6 horses/group) and administered gentamicin (6.6 mg/kg, IV, q 24 h for 4 days; group 1), a continuous IA infusion of gentamicin into the tarsocrural joint (50 mg/h for 73 hours; group 2), or both treatments (group 3). Serum, synovial fluid, and joint tissue samples were collected for measurement of gentamicin at various time points during and 73 hours after initiation of treatment. Gentamicin concentrations were compared by use of a Kruskal-Wallis ANOVA. RESULTS: At 73 hours, mean +/- SE gentamicin concentrations in synovial fluid, synovial membrane, joint capsule, subchondral bone, and collateral ligament of group 1 horses were 11.5 +/- 1.5 microg/mL, 21.1 +/- 3.0 microg/g, 17.1 +/- 1.4 microg/g, 9.8 +/- 2.0 microg/g, and 5.9 +/- 0.7 microg/g, respectively. Corresponding concentrations in group 2 horses were 458.7 +/- 130.3 microg/mL, 496.8 +/- 126.5 microg/g, 128.5 +/- 74.2 microg/g, 99.4 +/- 47.3 microg/g, and 13.5 +/- 7.6 microg/g, respectively. Gentamicin concentrations in synovial fluid, synovial membrane, and joint capsule of group 1 horses were significantly lower than concentrations in those samples for horses in groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IA infusion of gentamicin achieves higher drug concentrations in joint tissues of normal tarsocrural joints of horses, compared with concentrations after IV administration.     

Synovial Fluid Cytokines and Eicosanoids as Markers of Joint Disease in Horses

OBJECTIVE: To evaluate the value of various synovial fluid cytokines and eicosanoids to diagnose joint disease or categories of joint disease. STUDY DESIGN: Prospective acquisition of clinicopathologic data. ANIMALS OR SAMPLE POPULATION: Client-owned or donated horses: 50 joints with no evidence of disease; 28 joints with acute disease; 32 joints with chronic disease; 9 joints with cartilage damage and no other signs of joint disease. METHODS: Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), prostaglandin F1-alpha (PGF(1)-alpha), and leukotriene B(4) (LTB(4)), were measured in equine synovial fluid by immunoassay and categorized according to duration and degree of joint disease. Any test value for a given category that was different from normal was further analyzed for sensitivity (S), specificity (Sp), and operating point (most valid test cutoff value). Likelihood ratios and predictive values were calculated at the operating point. Mediator concentrations were correlated to synovial fluid white blood cell count. Tests were reported as poor, fair, good, or excellent based on predictive values of <.25,.25-.5,.5-.75, or >.75, respectively. RESULTS: TNF synovial fluid concentration as a predictor of joint disease was good, and the value of TNF (maximum S and Sp) indicating joint disease was >36 pg/mL. IL-1beta as a predictor of joint disease was good, and the value of IL-1beta indicating joint disease was >4.5 pg/mL. IL-6 concentration was an excellent predictor of joint disease. Any IL-6 in synovial fluid indicated joint disease and correlated highly with synovial fluid white blood cell count (P <.0001). PGE(2) was a good-excellent predictor of disease (positive predictive value [PPV] = 0.75), and the concentration indicating joint disease was >22.5 pg/mL. The diagnostic PGF(1)-alpha concentration indicating severe chronic joint disease was identified to be >16.5 pg/mL with very high sensitivity (S = 1) and specificity (Sp =.89). PGF(1)-alpha concentrations > 9.5 pg/mL had a good PPV (.69) and NPV (.6) for any joint disease. TBX(2) concentrations below 31.5 pg/mL (S =.57; Sp =.61) were a very good predictor of joint disease (PPV =.72). LTB(4) concentration appeared to be greater in severe acute joint disease than normal joints; this was not significant (P =.15) and correlated highly with synovial fluid white blood cell count (P =.0001). CONCLUSIONS: The ability of a single value from a joint in an adult horse predicting the presence of joint disease was often good (.5-.75), and was excellent (> or =.75) for IL-6 and PGE(2). TNF-alpha and IL-1beta were no more effective than white blood cell count in screening for joint disease. IL-6 was the most sensitive and specific for joint disease and could be an excellent screening test for the presence of joint disease when lameness is difficult to identify or is intermittent. PGE(2) would be a functional screening test for the presence of any joint disease and offers a differentiating feature because values were not influenced by white blood cell count. PGF(1)-alpha values > 16.5 pg/mL identified chronic severe joint disease and may be clinically useful when there are minimal radiographic changes but substantial articular cartilage degradation.     

The effect of implanting gentamicin-impregnated polymethylmethacrylate beads in the tarsocrural joint of the horse

OBJECTIVE: To determine the effect of intra-articular gentamicin-impregnated polymethylmethacrylate (PMMA) beads inserted in the equine tarsocrural joint on the synovial fluid, synovial lining, and cartilage, and to determine the peak and sustainable gentamicin concentrations in synovial fluid and plasma. STUDY DESIGN: Pharmacokinetic, cytologic, and histologic study of the effect of gentamicin-impregnated PMMA on normal equine tarsocrural joints. ANIMALS: Five healthy adult horses. METHODS: Gentamicin-impregnated PMMA bead strands (3 strands each of 40 beads, with each strand containing 100 mg gentamicin) were surgically inserted into one radiographically normal tarsocrural joint in 5 horses. Each horse had both joints flushed with 1 L of lactated Ringer's solution before bead administration. Synovial fluid total protein concentration, white blood cell (WBC) count, gentamicin concentration, synovial histology, cartilage integrity, and cartilage glycosaminoglycan (GAG) concentrations were determined. RESULTS: Gentamicin concentration (mean +/- SEM peak concentration, 27.9 +/- 2.27 microg/mL) occurred in the first 24 hours and remained above 2 microg/mL for 9 days. Gentamicin concentrations in control joints and the plasma remained below detectable levels. The synovial fluid WBC count for treated joints was increased compared with control joints for 72 hours, but was similar at day 6. The synovial protein concentration in gentamicin-treated joints remained increased for 21 days. Synovium in treated joints had diffuse synovitis, whereas control joints had less fibrovascular proliferation. Superficial cartilage erosion was present in all treated joints. There was no difference in the GAG content of treated and control joint cartilage. CONCLUSIONS: Short-term implantation of gentamicin (300 mg)-impregnated PMMA beads can provide therapeutic levels of gentamicin (>2 microg/mL) in the normal tarsocrural joint for 9 days; however, gentamicin-impregnated PMMA beads induce synovitis and superficial cartilage erosion. CLINICAL RELEVANCE: Temporary intra-articular administration of antibiotic-impregnated PMMA may be an effective way to treat septic joints that require constant high concentrations of antibiotics.     

Synovial fluid proteins in degenerative joint disease in dogs

Concentrations of three immunoglobulins, albumin, ceruloplasmin, alpha-2 macroglobulin and pregnancy zone protein were estimated by immunoelectrophoresis in paired samples of synovial fluid and serum from 12 dogs with degenerative joint disease (DJD) and six normal dogs. The ratios of synovial fluid to serum concentrations (SF/S) of the four non-immunoglobulins showed an almost inverse linear relationship with their molecular weight in both groups. The SF/S were higher in the DJD synovial fluid than in normal synovial fluid. The difference increased with increasing molecular weight and was highly significant for the largest molecules, reflecting an increased permeability and inflammation in the synovial membrane of DJD joints. The SF/S ratios of the three immunoglobulins studied were compared to the diffusion curves of the four non-immunoglobulins. The SF/S ratios of IgM from dogs with DJD exceeded those calculated from the molecular weights. The present observations support the concept that DJD should be considered an inflammatory disease and suggest that immunologic processes may initiate and/or sustain the inflammation.     

Digital blood flow and plasma endothelin concentration in clinically endotoxemic horses

OBJECTIVE: To measure plasma endothelin-1 (ET-1) concentrations and digital blood flow in clinically endotoxemic horses. ANIMALS: 36 adult horses that underwent emergency celiotomy for primary gastrointestinal tract disease. PROCEDURE: On days 2 and 5 following surgery, Doppler ultrasonographic digital arterial blood flow measurements were obtained. Hematologic and biochemical analyses were performed, and plasma concentrations of ET-1 and endotoxin (lipopolysaccharide) were determined. A scoring system based on 9 clinical variables was used to assign horses to group B (quartile with greatest cumulative score) or group A (remaining 3 quartiles). Follow-up at 2.5 years was obtained by telephone questionnaire. RESULTS: For all horses on day 2, median (interquartile values) plasma ET-1 concentrations were 1.4 (0.8, 1.7) pg/mL, whereas on day 5, plasma ET-1 concentrations were 1.0 (0.5, 1.6) pg/mL. On day 2, digital blood flow was 0.057 (0.02, 0.07) mL/min in group A horses and 0.035 (0.02, 0.03) mL/min in group B horses. On day 5, plasma ET-1 concentration was significantly (73%) higher in group B horses, compared with group A horses. Thirty of 36 horses were alive at 2.5 years; group A horses were more likely to have survived (odds ratio, 25; 95% confidence interval, 2.4 to 262). Significant associations were found between an increase in digital pulses, hoof wall temperatures, or both and increased digital blood flow (0.14 vs 0.04 mL/min) on day 2 and increased digital arterial diameter (0.32 vs 0.23 cm) on day 5. CONCLUSIONS AND CLINICAL RELEVANCE: Horses with more severe endotoxemia had decreased digital blood flow, increased plasma ET-1 concentrations, and decreased long-term survival.     

Concentrations of serum amyloid A in serum and synovial fluid from healthy horses and horses with joint disease

OBJECTIVE: To determine serum amyloid A (SAA) concentrations in serum and synovial fluid from healthy horses and horses with joint disease and assess the effect of repeated arthrocentesis on SAA concentrations in synovial fluid. Animals-10 healthy horses and 21 horses with various types of joint disease. PROCEDURES: Serum and synovial fluid samples were obtained from each horse. In 5 of the 10 healthy horses, arthrocentesis was repeated 9 times. Concentrations of SAA were determined via immunoturbidometry. RESULTS: Serum and synovial fluid SAA concentrations were less than the assay detection limit in healthy horses and did not change in response to repeated arthrocentesis. Synovial fluid SAA concentrations were significantly higher in horses with suspected bacterial joint contamination or infectious arthritis, or tenovaginitis than in healthy controls, and serum concentrations were significantly higher in horses with infectious conditions than in the other groups. Neither serum nor synovial fluid SAA concentrations in horses with low-inflammation joint conditions differed significantly from those in healthy controls. Concentrations of SAA and total protein in synovial fluid were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Synovial fluid SAA concentration was a good marker of infectious arthritis and tenovaginitis and appeared to reflect changes in inflammatory activity. The advantages of use of SAA as a marker include the ease and speed of measurement and the fact that concentrations in synovial fluid were not influenced by repeated arthrocentesis in healthy horses. Further study of the SAA response in osteoarthritic joints to assess its usefulness in diagnosis and monitoring of osteoarthritis is warranted.     

Effect of Four Antimicrobial Lavage Solutions on the Tarsocrural Joint of Horses

Three concentrations of povidone-iodine (0.1% w/v, 0.2% w/v, 0.5% w/v) and one concentration of chlorhexidine (0.5% w/v) were selected as antimicrobial joint lavage solutions. Through-and-through joint lavage was performed with one of these antimicrobial solutions on a tarsocrural joint of 12 horses. The contralateral tarsocrural joints (control limbs) were lavaged with a balanced electrolyte solution (BES). The effect of the lavage solution on the joints was evaluated with respect to lameness, foot flight pattern, soreness to joint palpation, articular and periarticular enlargement, and synovial fluid composition on Day 1,4, and 8 postlavage. On Day 8 postlavage, all horses were euthanized and the tarsocrural joints were examined.
All solutions induced a synovitis. Based on clinical assessment, synovial fluid protein levels, color, clarity, mucin clot forming ability, gross appearance of the joint at necropsy, and synovial membrane histologic evaluation, a similar, mild, transient, synovitis was induced by the BES and 0.1% povidone-iodine (PI) solution. The 0.2% PI solution induced a more prolonged neutrophilic response and poorer mucin clot forming ability in the synovial fluid as compared to the BES.
The 0.5% PI and 0.5% chlorhexidine solutions produced severe lameness, soreness to joint palpation, and limb enlargement. The elevated synovial fluid total protein content persisted significantly longer (p < 0.05) than the corresponding control (BES) solution. Histologic evaluation of the synovial membrane confirmed the presence of a moderate to severe neutrophilic synovitis in these treatment groups.     

Synovial fluid D-dimer concentration in foals with septic joint disease

Background: Increased synovial fibrinolytic activity (detected by increases in synovial D‐Dimer concentrations) has been observed in different joint diseases in humans and adult horses, presumably in order to minimize fibrin deposition within the joint and thus avoid its detrimental effects. Objective: To investigate fibrinolytic pathway activation in joint sepsis in foals by measuring synovial D‐Dimer concentrations. Animals: Eighteen septic foals with septic joints, 9 septic foals without septic joints, 9 systemically healthy foals with septic joint, and 3 controls are included. Methods: Prospective observational clinical study of foals admitted for septic arthritis. Synovial D‐Dimer concentration and routine synovial fluid analysis were performed. Diagnosis of joint sepsis was made whenever synovial total nucleated cell count was >30,000 cells/μL, synovial total protein >4 g/dL, and neutrophil percentage of >80%, or synovial fluid culture resulted positive. Results were compared among groups by general lineal models. Results: Synovial D‐Dimer concentration was significantly (P < .001) higher in the foals with septic joints compared with foals without joint disease (P < .001). Conclusions and Clinical Importance: Septic joint disease is associated with a marked increase of synovial D‐Dimer concentration (marked activation of the fibrinolytic activity) within the affected joint. Although further studies are needed, the measurement of synovial D‐Dimer concentration may be considered a complementary diagnostic marker of septic joint disease.     

Synovial fluid and plasma concentrations of ceftiofur after regional intravenous perfusion in the horse

OBJECTIVE: To determine radiocarpal (RC) joint synovial fluid and plasma ceftiofur concentrations after regional intravenous perfusion (RIP) and systemic intravenous (IV) administration. STUDY DESIGN: Experimental cross-over study. ANIMALS: Five normal adult horses. METHODS: One RC joint was randomly selected for RIP and the contralateral RC joint was sampled to determine intrasynovial ceftiofur concentrations after IV administration. Wash-out between IV and RIP was > or = 14 days. After surgical introduction of an intraarticular catheter, ceftiofur (2 g) was administered under general anesthesia either IV or by RIP after tourniquet application. Plasma and synovial fluid were collected over 24 hours. Samples were analyzed using high-performance liquid chromatography with ultraviolet detection and the results were statistically analyzed using a linear mixed effect model. RESULTS: Mean synovial fluid ceftiofur concentrations were consistently higher after RIP than after IV administration and were > 1 mug/mL (minimal inhibitory concentration [MIC] for common pathogens) for >24 hours. Mean synovial fluid peak concentration of ceftiofur after RIP and IV administration was 392.7+/-103.29 microg/mL at 0.5 hours postinjection (HPI) and 2.72+/-0.31 mug/mL at 1 HPI, respectively. Large variations in synovial fluid and plasma ceftiofur concentrations were observed between horses regardless of administration technique. RIP did not cause adverse effects. CONCLUSIONS: Under the present experimental conditions RIP with ceftiofur (2 g) induced significantly higher intraarticular antibiotic concentrations in the RC joint in comparison with IV administration. Moreover, after RIP, synovial fluid ceftiofur concentrations remain above the MIC for common pathogens (1 microg/mL) for > 24 hours. No adverse effects from the technique or the antibiotic were observed. CLINICAL RELEVANCE: RIP with high doses of ceftiofur may be a beneficial adjunctive therapy when treating equine synovial infections which are caused by cephalosporin susceptible microorganisms.     

Intraaticular treatment of tarsal degenerative joint disease in cattle.

Tarsal degenerative joint disease (DJD) in 12 cattle was classified as primary or secondary, based on age, evidence of hereditary or congenital joint conformation defects, faulty hindlimb alignment, duration and type of usage joints were subjected to, and history or signs of repeated trauma. Three of the cattle had bilateral primary tarsal DJD, 7 had bilateral secondary tarsal DJD, and 2 had secondary DJD of the left tarsus. Analyses of synovial fluid samples provided a means of characterizing pathologic changes of tarsal DJD, Results of blood and synovial fluid analyses were grouped in compilation of data for cattle affected with either primary or secondary tarsal DJD. Corticosteroids and a long-acting synthetic progestational agent were injected singly or in combination with aqueous antibiotics into affected tarsal joints. Tarsal joints of 5 of the cattle responded favorably to a single intraarticular treatment, as manifested by palliative relief and functionally usable joints. Seven joints of 5 cattle were subjected to repeated intraarticular treatment. Serial synovial fluid analyses in 7 of the cattle provided a means of assessing tarsal joint response to intraarticular treatment or to therapeutic arthrocentesis, exclusive of patient objective response. One cow developed a mild self-limiting bilateral postinjection synovitis that was resolved after the 2nd and final intraarticular injection. Usable function returned to tarsal joints of cattle that responded favorably to intraarticular treatment at different periods after single or repeated injections. Three cattle with advanced tarsal DJD experienced minor temporary relief and were euthanatized at their owner's request. Improvement did not occur in the tarsal joint of 1 cow subjected to therapeutic aspiration only. Intraarticular treatment in all cattle was considered supportive to the animal's well-being rather than curative.     

Pharmacokinetics and pharmacodynamics of enrofloxacin and a low dose of amikacin administered via regional intravenous limb perfusion in standing horses

OBJECTIVE: To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses. ANIMALS: 14 adult horses. PROCEDURES: Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint were collected prior to (time 0) and at intervals after tourniquet release for determination of drug concentrations. For pharmacokinetic-pharmacodynamic analyses, minimum inhibitory concentrations (MICs) of 16 microg/mL (amikacin) and 0.5 microg/mL (enrofloxacin) were applied. RESULTS: After RILP with enrofloxacin, 3 horses developed vasculitis. The highest synovial fluid concentrations of enrofloxacin and amikacin were detected at time 0; median values (range) were 13.22 microg/mL (0.254 to 167.9 microg/mL) and 26.2 microg/mL (5.78 to 50.0 microg/mL), respectively. Enrofloxacin concentrations exceeded MIC for approximately 24 hours in STIF and synovial fluid and for 36 hours in BMIF. After perfusion of amikacin, concentrations greater than the MIC were not detected in any samples. Effective therapeutic concentrations of enrofloxacin were attained in all samples. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with orthopedic infections, RILP of enrofloxacin (1.5 mg/kg) should be considered as a treatment option. However, care must be taken during administration. A dose of amikacin > 250 mg is recommended to attain effective tissue concentrations via RILP in standing horses.     

Assessment of the effects of age and joint disease on hydroxyproline and glycosaminoglycan concentrations in synovial fluid from the metacarpophalangeal joint of horses

OBJECTIVE: To assess the effects of age and joint disease on hydroxyproline and glycosaminoglycan (GAG) concentrations in synovial fluid from the metacarpophalangeal joint of horses and evaluate the association of those concentrations with severity of osteoarthritis and general matrix metalloproteinase (MMP) activity. SAMPLE POPULATION: Synovial fluid was collected from the metacarpophalangeal joints of foals at birth (n = 10), 5-month-old foals (10), 11-month-old foals (5), and adult horses (73). PROCEDURE: Hydroxyproline and GAG concentrations were determined in synovial fluid samples. The severity of osteoarthritis in adult joints was quantified by use of a cartilage degeneration index (CDI) and assessment of general MMP-activity via a fluorogenic assay. RESULTS: Hydroxyproline and GAG concentrations in synovial fluid were highest in neonates and decreased with age. Concentrations reached a plateau in adults by 4 years and remained constant in healthy joints. In synovial fluid from osteoarthritic joints, hydroxyproline and GAG concentrations were not increased, compared with unaffected joints, but hydroxyproline were significantly correlated with the CDI and general MMP activity. There was no significant correlation between GAG concentration and CDI value or MMP activity. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in hydroxyproline concentration in synovial fluid appeared to indicate damage to collagen of the articular cartilage. In joints with osteoarthritis, the lack of high GAG concentration in synovial fluid and the absence of a significant correlation between GAG concentration and CDI values or MMP activity may severely limit the usefulness of this marker for monitoring equine joint disease.     

Gentamicin concentrations in synovial fluid obtained from the tarsocrural joints of horses after implantation of gentamicin-impregnated collagen sponges

OBJECTIVE: To determine synovial fluid gentamicin concentrations and evaluate adverse effects on the synovial membrane and articular cartilage of tarsocrural joints after implantation of a gentamicin-impregnated collagen sponge. ANIMALS: 6 healthy adult mares. PROCEDURES: A purified bovine type I collagen sponge impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham-operated control joint. Gentamicin concentrations in synovial fluid and serum were determined for 120 hours after implantation by use of a fluorescence polarization immunoassay. Synovial membrane and cartilage specimens were collected 120 hours after implantation and evaluated histologically. RESULTS: Median peak synovial fluid gentamicin concentration of 168.9 microg/mL (range, 115.6 to 332 microg/mL) was achieved 3 hours after implantation. Synovial fluid gentamicin concentrations were < 4 microg/mL by 48 hours. Major histologic differences were not observed in the synovial membrane between control joints and joints implanted with gentamicin-impregnated sponges. Safranin-O fast green stain was not reduced in cartilage specimens obtained from treated joints, compared with those from control joints. CONCLUSIONS AND CLINICAL RELEVANCE: Implantation of a gentamicin-impregnated collagen sponge in the tarsocrural joint of horses resulted in rapid release of gentamicin, with peak concentrations > 20 times the minimum inhibitory concentration reported for common pathogens that infect horses. A rapid decrease in synovial fluid gentamicin concentrations was detected. The purified bovine type I collagen sponges did not elicit substantial inflammation in the synovial membrane or cause mechanical trauma to the articular cartilage.     

Bacterial culture of septic synovial structures of horses: Does a positive bacterial culture influence prognosis?

Reasons for performing study: The influence of synovial fluid culture on short‐ and long‐term prognosis of cases with septic synovitis requires study. Hypotheses: Horses with a positive bacterial culture from septic synovial fluid are less likely to survive or return to successful athletic function than those with a negative bacterial culture from septic synovial fluid. Methods: Records of mature horses presented to 2 equine referral hospitals for investigation of suspected septic synovitis were examined. Horses (n = 206) were included in the study if synovial fluid was submitted for full laboratory examination, including bacterial culture. A diagnosis of septic synovitis was based on a nucleated cell count >30 × 10⁹ cells/l or >90% neutrophils and other clinical, cytological and bacteriological parameters. Long‐term follow‐up was obtained by telephone questionnaire. Univariate analysis, using the Fisher's exact test, was used for all outcomes. Results: Fourteen (20.9%) of 67 horses with a positive bacterial culture from synovial fluid were subjected to euthanasia because of persistent synovial sepsis compared to 2 (1.44%) of 139 with negative bacterial cultures (P<0.001). Overall survival and successful long‐term return to function in horses with a positive bacterial culture was 50% (24/48 horses) compared to 70.5% (74/105) in culture negative horses (P = 0.01). In horses that survived to be discharged, successful long‐term return to function was not significantly different between culture positive and culture negative groups. Growth of Staphylococcus aureus from synovial fluid did not affect short‐term survival to discharge from the hospital compared to other positive bacterial culture; however, successful long‐term return to function was only 30.4% (4/13) in horses from which S. aureus was cultured compared to 73.9% (17/23) of horses in which other bacteria were cultured (P = 0.015). Conclusions and potential clinical relevance: Horses with a positive bacterial culture from a septic synovitis have a poorer prognosis for survival to discharge from hospital and overall long‐term return to function than horses that yielded no bacterial growth. When S. aureus was cultured, the long‐term prognosis was poorer.     

Plasma and Pulmonary Fluid Endothelin in Horses with Seasonal Recurrent Airway Obstruction

Background: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves.
Hypothesis: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission.
Animals: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected.
Methods: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA.
Results: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7–1.8) and venous (1.3, 1.2–1.7) plasma and in BALF (0.3, 0.2–0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21–50) were greater in affected horses during clinical exacerbation compared with remission ( P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses ( P < .05).
Conclusions and Clinical Importance: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.     

Determination of synovial fluid and serum concentrations, and morphologic effects of intraarticular ceftiofur sodium in horses

OBJECTIVES: To determine the serum and synovial fluid concentrations of ceftiofur sodium after intraarticular (IA) and intravenous (IV) administration and to evaluate the morphologic changes after intraarticular ceftiofur sodium administration. STUDY DESIGN: Strip plot design for the ceftiofur sodium serum and synovial fluid concentrations and a split plot design for the cytologic and histopathologic evaluation. ANIMALS: Six healthy adult horses without lameness. METHODS: Stage 1: Ceftiofur sodium (2.2 mg/kg) was administered IV. Stage 2: 150 mg (3 mL) of ceftiofur sodium (pHavg 6.57) was administered IA into 1 antebrachiocarpal joint. The ceftiofur sodium was reconstituted with sterile sodium chloride solution (pH 6.35). The contralateral joint was injected with 3 mL of 0.9% sterile sodium chloride solution (pH 6.35). Serum and synovial fluid samples were obtained from each horse during each stage. For a given stage, each type of sample (serum or synovial fluid) was collected once before injection and 12 times after injection over a 24-hour period. All horses were killed at 24 hours, and microscopic evaluation of the cartilage and synovium was performed. Serum and synovial fluid concentrations of ceftiofur sodium were measured by using a microbiologic assay, and pharmacokinetic variables were calculated. Synovial fluid was collected from the active joints treated during stage 2 at preinjection and postinjection hours (PIH) 0 (taken immediately after injection of either the ceftiofur sodium or sodium chloride), 12, and 24, and evaluated for differential cellular counts, pH, total protein concentration, and mucin precipitate quality. RESULTS: Concentrations of ceftiofur in synovial fluid after IA administration were significantly higher (P = .0001) than synovial fluid concentrations obtained after IV administration. Mean peak synovial fluid concentrations of ceftiofur after IA and IV administration were 5825.08 microg/mL at PIH .25 and 7.31 microg/mL at PIH 4, respectively. Mean synovial fluid ceftiofur concentrations at PIH 24 after IA and IV administration were 4.94 microg/mL and .12 microg/mL, respectively. Cytologic characteristics of synovial fluid after IA administration did not differ from cytologic characteristics after IA saline solution administration. White blood cell counts after IA ceftiofur administration were < or =3,400 cells/ML. The mean synovial pH of ceftiofur treated and control joints was 7.32 (range, 7.08-7.5) and 7.37 (range, 7.31-7.42), respectively. Grossly, there were minimal changes in synovium or cartilage, and no microscopic differences were detected (P = .5147) between ceftiofur-treated joints and saline-treated joints. The synovial half-life of ceftiofur sodium after IA administration joint was 5.1 hours. CONCLUSIONS: Synovial concentrations after intraarticular administration of 150 mg of ceftiofur sodium remained elevated above minimal inhibitory concentration (MIC90) over 24 hours. After 2.2 mg/kg IV, the synovial fluid ceftiofur concentration remained above MIC no longer than 8 hours. CLINICAL RELEVANCE: Ceftiofur sodium may be an acceptable broad spectrum antimicrobial to administer IA in septic arthritic equine joints.     

The influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion in the standing horse

This study investigated the influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion (IVRLP) and assessed the efficacy of low volume IVRLP. The front limbs of 9 horses were randomly assigned to 1 of 3 volume groups: 10 mL (Group 1), 30 mL (Group 2), or 60 mL (Group 3). A tourniquet was applied distal to the carpus and the limbs were perfused with 500 mg genta-micin diluted to the assigned volume via a catheter placed in the lateral palmar digital vein at the level of the proximal sesamoid bones. Synovial fluid samples were collected from the metacarpophalangeal joint at 30 minutes, followed by removal of the tourniquet. Gentamicin concentration in synovial fluid was detected using a fluorescence polarization immunoassay. There were no statistically significant differences among gentamicin concentrations in synovial fluid among perfusate volume groups. Mean gentamicin concentration in Group 1 (125.9 μg/mL) was higher than Group 2 (82.7 μg/mL) and Group 3 (56.1 μg/mL).     

Evaluation of avocado and soybean unsaponifiable extracts for treatment of horses with experimentally induced osteoarthritis

OBJECTIVE: To evaluate the use of a combination of avocado and soybean unsaponifiable (ASU) extracts for the treatment of experimentally induced osteoarthritis in horses. ANIMALS: 16 horses. PROCEDURES: Osteoarthritis was induced via osteochondral fragmentation in 1 middle carpal joint of each horse; the other joint underwent a sham operation. Horses were randomly allocated to receive oral treatment with ASU extracts (1:2 [avocado-to-soybean] ratio mixed in 6 mL of molasses; n = 8) or molasses (6 mL) alone (placebo treatment; 8) once daily from days 0 to 70. Lameness, response to joint flexion, synovial effusion, gross and histologic joint assessments, and serum and synovial fluid biochemical data were compared between treatment groups to identify effects of treatment. RESULTS: Osteochondral fragmentation induced significant increases in various variables indicative of joint pain and disease. Treatment with ASU extracts did not have an effect on signs of pain or lameness; however, there was a significant reduction in severity of articular cartilage erosion and synovial hemorrhage (assessed grossly) and significant increase in articular cartilage glycosaminoglycan synthesis, compared with placebo-treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Although treatment with ASU extracts did not decrease clinical signs of pain in horses with experimentally induced osteoarthritis, there did appear to be a disease-modifying effect of treatment, compared with findings in placebo-treated horses. These objective data support the use of ASU extracts as a disease-modifying treatment for management of osteoarthritis in horses.     

Cartilage oligomeric matrix protein and hyaluronan levels in synovial fluid from horses with osteoarthritis of the tarsometatarsal joint compared to a control population

REASONS FOR PERFORMING STUDY: Quantification of cartilage oligomeric matrix protein (COMP) levels within synovial fluid from the tarsometatarsal joint has not previously been reported and an effective synovial fluid marker would allow monitoring of disease progression and treatment. OBJECTIVES: To quantify levels of COMP and hyaluronan (HA) in synovial fluid from the tarsometatarsal joint, identify differences in levels from horses with osteoarthritis (OA) of the tarsometatarsal joint compared to a control population and to correlate levels with radiographic changes in horses with OA. METHODS: Synovial fluid was collected from the tarsometatarsal joint of 25 horses without hindlimb lameness (controls) and 25 lame horses, subjected to analgesia of the joint. COMP concentrations were measured using a homologous inhibition ELISA. Immunoblots of synovial fluid from 3 lame horses and 3 controls were performed to identify fragmentation of COMP. Hyaluronan (HA) concentration in synovial fluid was determined using a competition ELISA. Radiographs of the lame horses with OA were scored and correlated with levels of COMP and HA. RESULTS: Concentrations of COMP in OA of the tarsometatarsal joint were significantly lower than in the control samples. An additional fragment band of COMP (approximately 30 kDa) was identified on the immunoblots of the horses with OA and this fragment was not identified in controls. No significant difference was identified in the HA or HA:COMP ratio between lame and control horses. There was no correlation between levels of synovial fluid COMP and HA, and radiographic changes. CONCLUSIONS AND POTENTIAL RELEVANCE: Lowered levels of COMP in synovial fluid of tarsometatarsal joints correlates with the presence of osteoarthritis. However, a single value cannot be used to stage the disease process. Levels of HA may not be a useful marker for this disease. Decreased, rather than increased COMP levels, may reflect significant loss of cartilage in established osteoarthritis. A specific assay for the COMP fragment generated with osteoarthritis may allow the earlier detection of clinical cases.