Comparison of the effect of polysulfated glycosaminoglycan, corticosteroids, and sodium hyaluronate in the potentiation of a subinfective dose of Staphylococcus aureus in the midcarpal joint of horses

Four groups of 8 horses each had 1 midcarpal joint injected with 33 colony-forming units (CFU) of viable Staphylococcus aureus plus: 1 ml of saline solution (group 1, control), 250 mg of polysulfated glycosaminoglycan (PSGAG, group 2), 100 mg of methylprednisolone acetate (group 3), or 20 mg of sodium hyaulronate (group 4). Horses were euthanatized, and samples were obtained on the basis of clinical signs of septic arthritis that were nonresponsive to phenylbutazone administration. One group-1 horse, all 8 group-2 horses, 3 group-3 horses, and 4 group-4 horses were culture-positive for S aureus and had clinical signs, results of synovial fluid analysis, and histopathologic findings that were consistent with sepsis. The addition of 250 mg of PSGAG increased the development of sepsis significantly (P = 0.001), compared with results in control horses. Differences in the development of sepsis between horses injected with methylprednisolone acetate or sodium hyaluronate and control horses were not significant.     

Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses

Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (IA); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, IV, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), IA. Synovial fluid specimens were obtained at posttreatment hour (PTH) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at PTH 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at PTH 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens. At PTH 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and WBC count was higher (range, 88,000 to 227,200 cells/microliters) and predominantly neutrophilic (95 to 99%) at PTH 0 than before inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of equine complement activity by polysulfated glycosaminoglycans.

The ability of polysulfated glycosaminoglycans (PSGAG) to inhibit the complement cascade was evaluated. The role of complement in inflammation and infection has been well documented. Inhibition of the complement cascade by PSGAG could explain why intra-articularly administered PSGAG diminish diarthrodial joint inflammation and potentiate septic arthritis in horses. Hemolytic complement testing was performed to evaluate the effect of PSGAG on the equine classical and alternate pathways of complement, using rabbit erythrocytes as the target cells. Concentration of PSGAG between 0.2 mg/ml and 0.6 mg/ml significantly (P less than 0.05) inhibited equine complement in dose-related fashion. Further increase in complement inhibition was not observed at PSGAG concentration greater than 0.6 mg/ml. Difference was not apparent in the extent of inhibition of complement from each of the 4 horses tested. Polysulfated glycosaminoglycans appeared to inhibit the classical and alternate complement pathways equally, indicating possible effect on complement components common to both pathways. Heat inactivation of complement function completely inhibited (P less than 0.01) the hemolytic activity of the serum from all horses.     

Septic arthritis in 15 standardbred racehorses after intra-articular injection.

Case histories, results of synovial fluid analyses, treatment regimens and outcome are described for 15 adult Standardbred horses with confirmed post-injection septic arthritis. Joint sepsis followed injection of corticosteroids, hyaluronic acid, polysulphated glycosaminoglycan, or local anaesthetic. The median interval from injection to appearance of clinical signs was 2.5 days, and median interval from injection to referral was 9 days. The median initial synovial leucocyte count on admission was 57 x 10(9)/litre, but there was a wide range of values (18-258 x 10(9)/litre). The median synovial neutrophil percentage was 95% (77-99%). All bacterial isolates were Gram-positive cocci, 86% of which were staphylococci. All treated horses (12/15) initially received broad-spectrum parenteral antibiotic therapy, and the articulations of all horses except one were lavaged, either with non-surgical through-and-through techniques only (N = 3), or surgically with arthrotomy (N = 1) or arthroscopy (N = 7). The owners of all treated horses were contacted and racing records were consulted. Eleven of 12 horses returned to racing. Outcome was judged as either satisfactory (3/12) if the horse had returned to racing levels similar to or better than before treatment, or unsatisfactory (9/12) if the horse had poorer performance or could not return to racing. The 3 horses with satisfactory follow-up had been treated with arthroscopy and post-surgical closed suction drainage. The results of bacterial cultures suggest that the initial antimicrobial agents used should be effective against penicillin-resistant staphylococci.     

Serum and synovial fluid steady-state concentrations of trimethoprim and sulfadiazine in horses with experimentally induced infectious arthritis

The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 micrograms of TMP/ml and 4.75 micrograms of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination--30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, after inoculation with S aureus but before antimicrobial treatment, and after inoculation at various hourly intervals after oral administration of the TMP-SDZ combination. The TMP-SDZ combination was administered daily in the 2 dosages for 21 days. Samples were collected after day 3 of repetitive drug administration so that drug steady-state concentration would have been achieved. Serum and synovial fluid samples were analyzed for TMP and SDZ concentrations. Administration of the TMP-SDZ combination at a dosage of 30 mg/kg once daily was not effective in maintaining TMP or SDZ concentrations above the MIC of TMP-SDZ for the S aureus (0.25 and 4.75 micrograms/ml for TMP and SDZ, respectively) in the infected synovial fluid or in maintaining adequate TMP concentration in the serum. The alternative use of the TMP-SDZ combination at a dosage of 60 mg/kg given as 30 mg/kg every 12 hours was effective in maintaining serum and synovial fluid concentrations of TMP and SDZ that were greater than the MIC for the infective organism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional limb perfusion for antibiotic treatment of experimentally induced septic arthritis.

Septic arthritis was induced in one antebrachiocarpal joint of seven horses by the intra-articular injection of 1 mL Staphylococcus aureus suspension containing a mean of 10(5) colony-forming units. Twenty-four hours after inoculation, four horses were treated by regional perfusion with 1 g of gentamicin sulfate, and three horses received 2.2 mg/kg gentamicin sulfate intravenously (IV) every 6 hours. Synovial fluid was collected for culture and cytology at regular intervals, and the synovial membranes were collected for culture and histologic examination at euthanasia 24 hours after the first treatment. Gentamicin concentration in the septic synovial fluid after three successful perfusions was 221.2 +/- 71.4 (SD) micrograms/mL; after gentamicin IV, it was 7.6 +/- 1.6 (SD) micrograms/mL. The mean leukocyte count in the inoculated joints decreased significantly by hour 24 in the successfully perfused joints. Terminal bacterial cultures of synovial fluid and synovial membranes were negative in two horses with successfully perfused joints. S. aureus was isolated from the infected joints in all three horses treated with gentamicin IV.     

Comparison of two indirect techniques for local delivery of a high dose of an antimicrobial in the distal portion of forelimbs of horses

OBJECTIVE: To compare isolated limb retrograde venous injection (ILRVI) and isolated limb infusion (ILI) for delivery of amikacin to the synovial fluid of the distal interphalangeal and metacarpophalangeal joints and to evaluate the efficacy of use of an Esmarch tourniquet in standing horses. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses were randomly assigned in a crossover design. In ILRVI, the injection consisted of 1 g of amikacin diluted to a total volume of 60 mL administered during a 3-minute period. In ILI, the infusion consisted of 1 g of amikacin diluted to 40 mL administered during a 3-minute period followed by administration of boluses of diluent (82 mL total) to maintain vascular pressure. During ILI, the infusate and blood were circulated from the venous to the arterial circulation in 5-mL aliquots. Synovial fluid and serum samples were obtained to determine maximum amikacin concentrations and tourniquet leakage, respectively. RESULTS: Both techniques yielded synovial concentrations of amikacin > 10 times the minimum inhibitory concentration (MIC) for 90% of isolates (80 microg/mL) and > 10 times the MIC breakpoint (160 microg/mL) of amikacin-susceptible bacteria reported to cause septic arthritis in horses. These values were attained for both joints for both techniques. Esmarch tourniquets prevented detectable loss of amikacin to the systemic circulation for both techniques. CONCLUSIONS AND CLINICAL RELEVANCE: Both techniques reliably achieved synovial fluid concentrations of amikacin consistent with concentration-dependent killing for bacteria commonly encountered in horses with septic arthritis. Esmarch tourniquets were effective for both delivery techniques in standing horses.     

Concentration of cephalothin in body fluids and tissue samples of Thoroughbred horses

Cephalothin (CET) concentrations in body fluids (plasma, synovial fluid, pleural fluid, peritoneal fluid, and aqueous humor) and tissue samples (bone, lung, jejunum, hoof, and subcutaneous tissue) were investigated to consider the treatment of infectious diseases in horses. CET 22 mg/kg body weight was intravenously administered to 12 horses. Samples were collected from four different horses at 1, 3, and 5 hr after administration. The CET concentration in body fluids other than aqueous humor was maintained above the MIC₉₀ values of Streptococcus zooepidemicus and Staphylococcus aureus until 5 hr, but it was not maintained above that of S. aureus in bone. CET (22 mg/kg twice a day) is effective for septic arthritis, pleuritis, and peritonitis caused by gram-positive bacteria but ineffective for osteomyelitis.     

Multivariable analysis of factors influencing outcome of 2 treatment protocols in 128 cases of horses responding positively to intra-articular analgesia of the distal interphalangeal joint

REASONS FOR PERFORMING STUDY: There is limited knowledge available of factors influencing response to treatments of the DIP-joint in horses with lameness responding to diagnostic analgesia of the DIP-joint. For this reason a multivariable statistical analysis was performed. HYPOTHESIS: Horses with lameness reduced by > or = 75% 10 min after intra-articular analgesia of the DIP-joint, can be treated successfully by intra-articular medication of the joint. Multiple factors influence the response to treatment. METHODS: The study was performed retrospectively based on clinical records of horses treated with either polysulphated glycosaminoglycan (PSGAG) or methylprednisolone acetate (MPA) in the DIP-joint between January 1996 and January 2003. Information was collected from clinical records and from the owners of the horses via a detailed questionnaire, in which they described their perception of the outcome a minimum of one year after treatment. Allocation of the horses to the 2 treatment groups was done mainly because of a change in treatment policy. In Regime A all horses received 3 intra-articular injections of PSGAG approximately 8 days apart, whereas in Regime B all horses received a single intra-articular injection of MPA as a first treatment. If the horse did not improve sufficiently to return to work by 4 weeks, a series of 3 intra-articular PSGAG injections was administered. RESULTS: Of the horses receiving Regime A, 67% had a successful outcome, compared with 46% of the group receiving Regime B. A significantly better result was obtained in dressage horses than in jumping horses (eventing and showjumping). Other variables such as age, duration of lameness, distribution of lameness, degree of lameness, response to DIP-joint analgesia and radiographic observations were also associated with success of treatment. CONCLUSIONS AND POTENTIAL RELEVANCE: There is a rationale for using either PSGAG or MPA intra-articularly in the treatment of lameness, reduced > or = 75% within 10 min of analgesia of the DIP-joint.     

Open drainage, intra-articular and systemic antibiotics in the treatment of septic arthritis/tenosynovitis in horses.

Open drainage was used to treat 26 horses with persistent or severe septic arthritis/tenosynovitis. Infected synovial structures were drained through a small (3 cm) arthrotomy incision that was left open and protected by a sterile bandage. Joint lavage was performed in all 26 horses. In addition to systemic antibiotics, 23 of these horses were also treated with intra-articular antibiotics; amikacin (17 horses), gentamycin (2 horses), cefazolin (2 horses), and 2 horses were injected at different times with gentamycin and amikacin. The infection was eliminated from the involved synovial structures in 25 of 26 horses; 24 survived and were released from the hospital. The arthrotomy incisions healed by granulation in 16 horses; in 9 horses the arthrotomy incision was sutured closed once the infection was eliminated. Seventeen horses returned to soundness and resumed athletic function. Open drainage was an effective method of achieving chronic drainage from a joint or tendon sheath. It is indicated in horses that have established intra-synovial infections or in horses that do not respond to joint lavage through needles.     

Polysulfated glycosaminoglycan accelerates net synthesis of collagen and glycosaminoglycans by arthritic equine cartilage tissues and chondrocytes

Low molecular weight polysulfated glycosaminoglycan (PSGAG) stimulated net collagen and glycosaminoglycan synthesis by normal and arthritic equine fetlock cartilage tissues in organ culture. Arthritic tissues were more sensitive to PSGAG stimulation. The rates of cartilage-specific type-II collagen and chondroitin sulfate-rich glycosaminoglycan synthesis by confluent chondrocyte cell cultures obtained from normal and arthritic equine cartilage tissues were increased by 25 and 50 mg of PSGAG/ml. Cells from arthritic cartilage were also more sensitive to the presence of PSGAG. In addition, concentrations of PSGAG (25 and 50 mg/ml) approximate to those in synovial fluid after intra-articular injection of 250 mg of PSGAG inhibited the rate of collagen and glycosaminoglycan degradation in cell culture. These findings suggest that PSGAG may have a role in the healing of mild cartilage degeneration by encouraging the production of replacement hyaline matrix materials, while delaying their subsequent degradation. In contrast, growth of cell cultures was inhibited by PSGAG, suggesting that these compounds may fail to stimulate chondrocyte replication, a prerequisite for tissue regeneration. Nonetheless, these observations provide direct evidence of a truly chondroprotective role for low molecular weight PSGAG in the treatment of equine degenerative joint disease.     

Effect of gentamicin sulfate and sodium bicarbonate on the synovium of clinically normal equine antebrachiocarpal joints

The effect of gentamicin sulfate, unbuffered and buffered with sodium bicarbonate, on synovial fluid and membrane of clinically normal equine joints was evaluated. Thirty-six adult horses with clinically normal antebrachiocarpal joints were allotted to 6 treatment groups of 6 horses each. One antebrachiocarpal joint in each horse was chosen for treatment. Group-1 horses were given gentamicin (3 ml; 50 mg/ml); group-2 horses were given sodium bicarbonate (3 ml; 1 mEq/ml); group-3 horses were given gentamicin (3 ml; 50 mg/ml) and sodium bicarbonate (3 ml; 1 mEq/ml); group-4 horses were not treated; and horses of groups 5 and 6 were given polyionic physiologic solution (3 and 6 ml, respectively). Synovial fluid specimens were obtained from 5 horses of each group for cytologic analysis at postinjection hours (PIH) 0, 24, 72, and 192 and for pH determination at PIH 0, 0.25, 0.5, 1, 4, 8, 24, 72, and 192. The sixth horse of each group was euthanatized at PIH 24, and the synovial membrane of the treated and contralateral (nontreated) antebrachiocarpal joints was examined macroscopically and microscopically. After intra-articular gentamicin administration, the mean synovial fluid pH was lowest (5.98) at PIH 0.25, but by PIH 8, it was not significantly different from the control value (group-5 horses). When sodium bicarbonate was combined with gentamicin before intra-articular administration, the mean synovial fluid pH was lowest (7.07) at PIH 0.25, but by PIH 1, it was not significantly different from the control value (group-6 horses).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intra-articular administration of methylprednisolone acetate on normal articular cartilage and on healing of experimentally induced osteochondral defects in horses.

The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full-thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Staphylococcal septic arthritis in three horses.

Three horses were diagnosed as having monarticular septic arthritis due to Staphylococcus aureus on the basis of culture of articular cartilage, synovial membrane and/or synovial fluid. The organisms were all well recognised human phage types and in two cases demonstrated beta-lactamase (penicillinase) activity. Details of case histories are presented and the bacteriological techniques and antibiotic management with cloxacillin, methicillin and penicillin discussed. Following treatment, sterile cultures of synovial fluid were achieved in all cases, but in two horses the infections resulted in degenerative articular changes. This necessitated arthrodesis of the fetlock joint in one case.     

A retrospective study of 192 horses affected with septic arthritis/tenosynovitis.

The medical records of 192 horses with septic arthritis/tenosynovitis 1979-1989 were reviewed. Forty-three horses developed infection after an intra-articular injection, 46 following a penetrating wound, 25 following surgery, 66 were foals less than 6 months old, and 12 were adult horses without a known aetiology. Haematogenous infection of a joint occurs in adult horses and should be considered as a differential diagnosis in horses with an acute onset of severe lameness. The aetiology of the infection had a significant effect on the type of bacteria identified by culture. Staphylococcus was cultured from most of the horses that developed infection following a joint injection or surgery, 69% of the horses from which an organism was identified. Horses that developed infection secondary to a penetrating wound frequently provided cultures of more than one organism; Enterobacteriaceae and anaerobes were more frequently isolated in this group. The most common organisms isolated from foals were Enterobacteriaceae; E. coli was identified in more than 27% of the foals. The hock was the most frequently involved joint. Multiple treatments were used over the 10-year period of study. Survival rates were lowest in foals; only 45% survived to be released from the hospital. Survival was greater in adult horses; 85% of the horses that were treated were released from the hospital. Survival was significantly greater in horses with septic tenosynovitis; all 14 of the horses that were treated survived. Survival was not significantly affected by the joint involved or by the type of bacteria cultured from the synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Povidone-iodine lavage treatment of experimentally induced equine infectious arthritis

Both tarsocrural joints of 4 horses were inoculated with 1.5 X 10(5) colony-forming units of Staphylococcus aureus. On days 1, 3, and 6, each horse had one tarsocrural joint lavaged with a balanced electrolyte solution and had the contralateral tarsocrural joint lavaged with 0.1% povidone-iodine solution. All horses were orally administered trimethoprim (5 mg/kg)/sufadiazine (25 mg/kg) combination twice daily and phenylbutazone (2 g) once daily for the duration of the study (21 days). On days 0, 1, 3, 6, 9, 14, and 21, synovial fluid specimens were collected and analyzed for color, clarity, total protein concentration, WBC count and differential, and mucin clot-forming ability. Synovial fluid specimens collected on days 1, 3, 6, 9, 14, and 21 were bacteriologically cultured. On day 21, all horses were euthanatized, the tarsocrural joints were opened and examined, synovial membrane specimens were collected, bacteriologically cultured, and histologically evaluated, and articular cartilage specimens were histochemically evaluated. Repeated measures analysis of variance were used to evaluate differences between lavage solutions and among days for objective measurements. A paired t test was used to evaluate differences between solutions for the indices of synovial membrane inflammation and articular cartilage staining intensity with safranin-O-fast green. To be considered significant, the probability of a type-I error was less than 0.05. Significant differences were not found between joints lavaged with electrolyte solution vs povidone-iodine solution for synovial total protein concentration, WBC count, results of synovial fluid and membrane bacteriologic culture, synovial membrane inflammation, or articular cartilage glycosaminoglycan concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fragment size is associated with post-operative complications following elective arthroscopy of the tibiotarsal joint of horses

The objective of this retrospective study was to determine the occurrence of joint-related complications after elective arthroscopy of the tibiotarsal joint (TTJ) in 329 horses, and the association with specific clinical parameters. Data were collected from medical records of horses undergoing elective tibiotarsal joint arthroscopy for fragment removal. Exact conditional univariate regression was used to determine significant risk factors for joint-related post-operative complications.Of 485 joints, 2 (0.4%) developed surgical site infection, 4 (0.8%) developed septic arthritis, 1 (0.2%) developed synovial fistula. There was a significantly increased odds of having septic arthritis as height and length of the distal intermediate ridge of the tibia (DIRT) lesion increased. The median height and length of the DIRT fragments in affected cases was 13.5 mm and 18.0 mm, respectively. For each unit (1 mm) increase in height, there was a 42% increase in the risk of septic arthritis occurrence (P = 0.0042), and a 15% increase for each unit increase in length (P = 0.035). Horses were significantly less likely to develop septic arthritis when suture smaller than USP 0 was used.Horses with larger osteochondritis dissecans lesions of the DIRT region have an increased risk of developing septic arthritis following fragment removal.     

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.     

The efficacy of systemically administered anti-arthritic drugs in an induced equine carpitis model

The efficacy of two systemically administered drugs for the treatment of equine joint injuries was assessed in a randomized blinded trial using the chemically induced equine carpitis model previously used to determine the dose and efficacy of both products. After a 10-day acclimation period, carpitis was induced by intracarpal injection of Complete Freund's Adjuvant (CFA) in twenty mature horses free of clinical and radiographic evidence of synovitis or DJD. Five days after model induction, the horses were stratified based on lameness evaluation and randomly assigned to 2 groups of 10 horses each.Parameters evaluated included lameness score, maximum range of carpal flexion, carpal circumference, stride length, and synovial fluid protein. These parameters were measured prior to model induction, 5 days after model induction (immediately prior to initial treatment) and once weekly for 6 weeks. Radiographs of the carpus were taken prior to model induction and 6 weeks. after treatment began. Treatment began 5 days after model induction. One group of 10 horses received 40 mg sodium hyaluronate by intravenous injection weekly for 3 weeks and the other group of 10 horses received intramuscular injections of 500 mg PSGAG every 4 days for 7 treatments.Both treatment groups showed significant improvement from pretreatment baseline values (based upon percent recovery to normal pre-model induction values) for lameness score, stride length and maximum carpal flexion (p<0.05) at each post treatment evaluation. The PSGAG treated group had significant improvement in synovial fluid protein at post treatment weeks 2 and 3. The improvement (percent recovery) in the PSGAG treated group was significantly (p<0.05) better than that of the intravenous sodium hyaluronate treated group for stride and flexion at post treatment weeks 1 through 6, for lameness score at post treatment weeks 1 through 3 and for carpal circumference at post treatment week 4.Both intravenous sodium hyaluronate and intramuscular PSGAG induced significant improvement in clinical lameness parameters; intramuscular PSGAG yielded consistently better results in this experimental model.     

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.