In this preliminary investigation, various hematologic variables potentially influential in determining the degree of blood viscosity were evaluated in 10 Thoroughbred horses subjected to competitive acute running exercise. Following completion of sprints over a distance of 1.25 miles, mean percent (+/- SD) increases in PCV (38.3 +/- 12.9%), RBC (47.8 +/- 15.3%), and rouleaux index (232.7 +/- 176.8%) were recognized. Simultaneous increases in total plasma protein (28.3 +/- 5.31%), serum albumin (26.7 +/- 6.80%), alpha 1-globulin (60.0 +/- 49.0%), alpha 2-globulin(25.5 +/- 27.9%), beta 1-globulin (46.7 +/- 21.1%), beta 2-globulin (35.0 +/- 50.6%), gamma 1- and 2-globulins (38.7 +/- 29.6%), and plasma fibrinogen (12.5 +/- 10.4%) concentrations increased simultaneously. Horses also had consistent decreases in albumin:globulin ratio (- 10.0 +/- 7.43%). Alterations in these hematologic values after acute running exercise in Thoroughbred horses accompanied increases in serum (69.3 +/- 39.7%), plasma (39.7 +/- 11.9%), and blood (134.7 +/- 55.3%) viscosity.

Viscosity of synovial fluid (SF) from 29 clinically normal horses was determined by use of a rotational cone and plate microviscosimeter. Total protein concentration in the SF of the 29 horses, as measured with a refractometer, was < 2.5 g/dl. When the Coomassie brilliant blue test was used to determine total protein concentration in SF for 15 horses, the mean value was 1,088 mg/dl. Viscosity values at 60, 30, 12, 6, 3, and 1.5 revolutions/min (rpm) spindle speed were 4.41 +/- 1.54 centipoise (cp), 5.29 +/- 1.94 cp, 6.76 +/- 2.76 cp, 8.52 +/- 4.27 cp, 10.41 +/- 6.30 cp, and 13.07 +/- 9.05 cp, respectively. Synovial fluid viscosity increased with decreasing rpm and shear rate, but the shape of the curve for each horse fitted the asymptotic curve. The rotational cone and plate microviscosimeter was an accurate instrument in measuring SF viscosity at multiple rpm or shear rates in horses. The values obtained on clinically normal horses in this study will serve as a baseline for comparison in the evaluation of horses with joint disease.

In recent years, exercise on a water treadmill has come to have great relevance in rehabilitation and training centres for sport horses. Its use exploits certain physical properties of water, related to the fundamental principles of hydrodynamics, such as buoyancy, viscosity, hydrostatic pressure, and water temperature. These properties together with deliberate specification of the depth of the water and the velocity of the treadmill provide a combination of parameters that can be varied according to the purpose of the rehabilitation or training programme, the disease to rehabilitate, or the healing phase. In the current article, kinematic adaptations to exercise on a water treadmill and the direct application of such exercise to the rehabilitation of superficial and deep digital flexor tendon and accessory ligament injuries and back and joint diseases are described.

OBJECTIVE To assess rheological properties and in vitro diffusion of poloxamer 407 (P407) and butorphanol-P407 (But-P407) hydrogels and to develop a sustained-release opioid formulation for use in birds. SAMPLE P407 powder and a commercially available injectable butorphanol tartrate formulation (10 mg/mL). PROCEDURES P407 and But-P407 gels were compounded by adding water or butorphanol to P407 powder. Effects of various concentrations of P407 (20%, 25% and 30% [{weight of P407/weight of diluent} × 100]), addition of butorphanol, and sterilization through a microfilter on rheological properties of P407 were measured by use of a rheometer. In vitro diffusion of butorphanol from But-P407 25% through a biological membrane was compared with that of a butorphanol solution. RESULTS P407 20% and 25% formulations were easily compounded, whereas it was difficult to obtain a homogenous P407 30% formulation. The P407 was a gel at avian body temperature, although its viscosity was lower than that at mammalian body temperature. The But-P407 25% formulation (butorphanol concentration, 8.3 mg/mL) was used for subsequent experiments. Addition of butorphanol to P407 as well as microfiltration did not significantly affect viscosity. Butorphanol diffused in vitro from But-P407, and its diffusion was slower than that from a butorphanol solution. CONCLUSIONS AND CLINICAL RELEVANCE But-P407 25% had in vitro characteristics that would make it a good candidate for use as a sustained-release analgesic medication. Further studies are needed to characterize the pharmacokinetic and pharmacodynamic properties of But-P407 25% in vivo before it can be recommended for use in birds.

Packed cell volume and plasma total protein (TP), serum albumin (Alb) and globulin (Glb), and plasma ionized calcium (PCa) concentrations, blood viscosity (BV), and plasma viscosity (PV) were measured in 42 horses at rest and after the cross country jumping phase of a horse trial competition. The BV and Pv were determined at 6 shear rates (230, 115, 46, 23, 11.5, 5.75 s 1), using a digital rotational cone and plate microviscometer. A paired t-test was used to determine differences between PCV, TP, Alb, Glb and PCa values at rest and after exercise. The PCV, TP, Alb, and Glb values increased (P < 0.05) in horses after exercise. The PCa concentration decreased (P < 0.05) in horses after exercise. Mean BV and Pv in the 42 horses at rest and after exercise were fitted to an asymptotic function. Significant (P < 0.05) correlation at aH shear rates was seen between BV at rest and PCV, TP, Alb, Glb, and PCa values at rest; and between BV after exercise and PCV, TP, Alb, Glb, and PCa values after exercise. Significant correlation was not seen between PV at rest and TP, Alb, Glb, and PCa at rest, or between PV after exercise and TP, Alb, Glb, and PCa concentrations after exercise at any shear rate.

Physical, biochemical, and cytologic properties of synovial fluid from digital flexor tendon sheaths of clinically normal horses were investigated. Tendon sheath fluid was pale yellow, clear, and did not clot. Volume of fluid within a tendon sheath varied minimally, with a mean of 2.11 ml. Total erythrocyte counts were higher than values observed in normal equine joint fluid, whereas values for total leukocyte count (770 +/- 73 cells/mm3), viscosity (6.05 +/- 0.58 cs), and protein concentration (7.87 +/- 0.03 mg/ml) were similar to those in joint fluid. Large mononuclear cells were the predominant synovial fluid cell type. Mean hyaluronic acid concentration (0.74 +/- 0.02 mg/ml) and mucinous precipitate quality were lower than values in joint fluid.

Eight mature horses with no prior signs of joint disease or history of intra-articular therapy were treated with 8 weekly intra-articular injections of methylprednisolone acetate. Treatments were given at a dose of 120 mg/joint into the right radiocarpal and intercarpal joints, with the left joints as untreated controls. Articular cartilage samples were obtained at necropsy 1, 4, and 8 weeks after the last injection. Compared with controls, cartilage from injected joints had loss of hematoxylin basophilia and decreased intensity of staining in safranin O fast green dye. Chondrocyte necrosis and hypocellularity were observed in all samples of cartilage from treated joints. Proteoglycan content and its rate of synthesis were reduced. There was a progressive loss of proteoglycan content, whereas proteoglycan synthesis increased somewhat 4 and 8 weeks after treatment. Collagen content was unchanged, but its rate of synthesis was markedly inhibited. Collagen synthesis did not recover, but remained decreased at 5 to 15% of the values from untreated cartilage. Water percentage was increased, but fibronectin content was not significantly different. A single injection of methylprednisolone acetate was also given into the right metacarpophalangeal joints of 3 of the 8 horses in this group, with the left joints serving as untreated controls. Sixteen weeks after the treatment, cartilage of the treated joints had a loss of histochemical staining and proteoglycan content was reduced to 50% of control values. The mean rate of proteoglycan synthesis and mean fibronectin content were increased, but the differences were not statistically significant (P greater than 0.05). Other variables were essentially unchanged. For control studies, the right carpal joints of 2 additional horses were injected with the drug suspension vehicle. All measurements, compared with those of samples from untreated joints, were unchanged. On the basis of our findings, we concluded that the effects on cartilage of intra-articular injections of methylprednisolone acetate were not ameliorated at 8 weeks after 8 weekly injections or 16 weeks after a single injection. Cartilage remained biochemically and metabolically impaired.

OBJECTIVE To determine the physiochemical properties and pharmacokinetics of 3 midazolam gel formulations following buccal administration to dogs. ANIMALS 5 healthy adult hounds. PROCEDURES In phase 1 of a 2-phase study, 2 gel formulations were developed that contained 1% midazolam in a poloxamer 407 (P1) or hydroxypropyl methylcellulose (H1) base and underwent rheological and in vitro release analyses. Each formulation was buccally administered to 5 dogs such that 0.3 mg of midazolam/kg was delivered. Each dog also received midazolam hydrochloride (0.3 mg/kg, IV). There was a 3-day interval between treatments. Blood samples were collected immediately before and at predetermined times for 8 hours after drug administration for determination of plasma midazolam concentration and pharmacokinetic analysis. During phase 2, a gel containing 2% midazolam in a hydroxypropyl methylcellulose base (H2) was developed on the basis of phase 1 results. That gel was buccally administered such that midazolam doses of 0.3 and 0.6 mg/kg were delivered. Each dog also received midazolam (0.3 mg/kg, IV). All posttreatment procedures were the same as those for phase 1. RESULTS The H1 and H2 formulations had lower viscosity, greater bioavailability, and peak plasma midazolam concentrations that were approximately 2-fold as high, compared with those for the P1 formulation. The mean peak plasma midazolam concentration for the H2 formulation was 187.0 and 106.3 ng/mL when the midazolam dose administered was 0.6 and 0.3 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that buccal administration of gel formulations might be a viable alternative for midazolam administration to dogs.

The effects of furosemide and pentoxifylline on blood flow properties in horses were investigated. Hematologic and rheologic changes were examined in 4 horses before and 3 minutes after administration of epinephrine (1 mg, IV). The next day, hemorheologic changes were determined before and 3 hours after administration of furosemide (1 mg/kg of body weight, IM), and after administration of epinephrine at the sampling at 3 hours. Hematologic and rheologic changes were evaluated weekly in 3 horses given pentoxifylline (8.5 mg/kg, q 12 h, PO) for 28 days. In addition, hemorheologic responses to epinephrine were determined on days 0, 14, and 28 of pentoxifylline treatment. Neutrophil filtration studies were also performed 2 hours after IV administration of pentoxifylline (8.5 mg/kg). Postepinephrine values for PCV, RBC and WBC counts, and blood viscosity were greater than preepinephrine values. Erythrocyte sedimentation rates decreased after epinephrine, whereas RBC filterability did not change. Treatment with furosemide was associated with increases in mean RBC hemoglobin concentration and blood viscosity. Filterability of RBC did not change. Treatment with pentoxifylline resulted in an increase in RBC filterability and erythrocyte sedimentation rate and a decrease in PCV; however, mean values for hematocrit and RBC count did not change. Treatment with pentoxifylline did not result in a change in resting blood viscosity, but markedly reduced the postepinephrine increase in blood viscosity. Neither IV nor orally administered pentoxifylline had an effect on neutrophil filtration. It was concluded that pentoxifylline has beneficial effects on RBC filterability and postepinephrine changes in blood viscosity, which may contribute to improvements of microcirculatory blood flow. In addition, furosemide may exacerbate exercise-associated hyperviscosity in horses.

Intraocular pressure (IOP) was determined in right eyes of 20 healthy dogs after sodium hyaluronate (1%, n = 5), sodium chondroitin sulfate (4%) and sodium hyaluronate (3%, n = 5), hydroxypropyl methylcellulose (2%, n = 5), or balanced salt solution (control, n = 5) was injected into the anterior chamber. Applanation tonometry was used to measure IOP in both eyes of each dog for up to 168 hours. The 3 viscoelastic solutions resulted in an increased mean IOP by postinjection hours (PIH) 2; from PIH 12 until PIH 72, the IOP was significantly (P less than 0.001) lower than baseline. The control group did not have an increase in IOP at PIH 2; mean IOP decreased below baseline measurements within 2 hours and remained lower until PIH 72. Mean differences in IOP were not found among treated eyes (P = 0.50), and a significant interaction of any treated eyes in a group was not detected (P = 0.21). By PIH 168, the IOP approached baseline values in all groups.