Inflammatory Response of Healthy Horses Subjected to Small Colon Enterotomy and Treated or Not With Heparin

The acute phase response is a response to injury and depends on the severity of the trauma. Heparin is routinely used for postsurgical treatment of horses to prevent abdominal adhesions; however, its effect on inflammation is unknown. This study aimed to assess systemic inflammatory response of horses subjected to small colon enterotomy and to evaluate heparin effects on postsurgical inflammation. Ten adult horses were subjected to small colon enterotomy and were assigned to a control or a treatment group. Both groups received prophylactic antibiotics and flunixin, and the treatment group received 150 IU/kg heparin subcutaneously after surgery and every 12 hours for five days. WBC counts, peritoneal fluid evaluation, determination of serum and peritoneal haptoglobin (Hp), and serum amyloid A (SAA) were performed before, 12 hours, and 1, 2, 4, 6, 10, and 14 days after enterotomy. Forty-eight hours after surgery, a significant increase in serum Hp was observed in the control group, and SAA concentrations increased significantly in the both groups between 24 hours, 48 hours, and 4 days after surgery. The SAA and serum Hp concentrations produced no significant differences between the groups. Peritoneal Hp increased significantly in the control group 4 days after surgery and was significantly higher in the control group than in the treated group 14 days after surgery. Serum Hp and SAA identified the acute phase response changes faster, however, were not able to identify differences between groups. Peritoneal Hp concentrations identified inflammatory differences between the groups 14 days after surgery; the difference suggests that heparin may act decreasing inflammation.     

Serum amyloid A in the serum and milk of ewes with mastitis induced experimentally with Staphylococcus epidermidis

Mastitis was induced experimentally in ewes with Staphylococcus epidermidis, and the concentrations of serum amyloid A (SAA) in milk and serum, and the somatic cell counts and bacteria in the milk were determined for up to 10 weeks in two experiments, each examining five infected and five control ewes. The somatic cell counts peaked eight hours after infection and preceded an increase in SAA in milk. A maximum concentration of 6460 microg/ml SAA was recorded in milk from the infected sheep, compared with a mean concentration of 1.4 microg/ml in the control sheep. The mean peak concentration of SAA in serum (206.8 microg/ml) occurred earlier (one day after infection) than in milk. The serum concentration of SAA in the healthy animals ranged from 0 to 29.4 microg/ml. There was no correlation between the concentrations of SAA in serum and milk.     

Effects of ophthalmic disease on concentrations of plasma fibrinogen and serum amyloid A in the horse

Reasons for performing study: There is little scientific information available about the ability of ocular disease to cause a systemic inflammatory response. Horses are frequently affected with ocular disease and ensuring their systemic health prior to performing vision saving surgery under anaesthesia is essential for the successful treatment of ophthalmic disease. Hypothesis: Ocular disease will cause elevations in the concentration of the acute phase proteins fibrinogen and serum amyloid A in peripheral blood. Methods: Whole blood and serum samples were obtained from 38 mature horses with ulcerative keratitis or uveitis and no evidence of systemic disease, 9 mature horses with no evidence of ocular or systemic disease (negative controls) and 10 mature horses with systemic inflammatory disease and no evidence of ocular disease (positive controls). Blood samples were assayed for concentrations of the acute phase proteins fibrinogen and serum amyloid A. Results: Fibrinogen and serum amyloid A were significantly different in the positive control group compared to the negative control, corneal disease and uveitis groups (P<0.126). There was no significant difference between the negative control, corneal disease and uveitis groups (P<0.001). Conclusions: Ulcerative keratitis and anterior uveitis are not associated with elevated concentrations of the acute phase proteins fibrinogen and serum amyloid A in peripheral blood. Potential relevance: When the clinician is presented with a patient with ocular disease and elevated plasma fibrinogen or serum amyloid A concentrations, a nonocular inflammatory focus should be suspected.     

Effects of exploratory laparotomy on plasma and peritoneal coagulation/fibrinolysis in horses

Plasma and peritoneal fluid samples were collected before and after surgery from 6 horses undergoing a ventral midline exploratory laparotomy and from 6 anesthetized control horses. Coagulation/fibrinolytic components measured in the plasma and peritoneal fluid of these horses included the functional activity of antithrombin III, alpha-2 antiplasmin, plasminogen, and protein C, and the concentrations of fibrinogen and fibrin degradation products. Peritoneal fluid antithrombin III, fibrin degradation products, and plasminogen values were significantly increased after surgery (over time) in principal horses. Compared with control horses, postoperative peritoneal fluid from horses undergoing laparotomy had significantly increased antithrombin-III activity at 12 and 72 hours, alpha-2 antiplasmin activity at 24 hours, fibrin degradation product concentrations at 6, 12, 24, 72, 96, and 144 hours, plasminogen activity at 6, 12, 24, 48, 72 and 96 hours, and protein-C activity at 12, 24, 72, and 96 hours. There were no significant changes in the peritoneal fibrinogen concentration in principal horses. Plasma plasminogen activity was significantly decreased at 24 hours after surgery in principal horses, compared with controls. Changes were minimal in the remaining plasma coagulation/fibrinolytic components of horses undergoing laparotomy. Plasma and peritoneal fluid values of anesthetized control horses did not change.     

Effects of indwelling nasogastric intubation on gastric emptying of a liquid marker in horses

OBJECTIVE: To determine the effects of indwelling nasogastric intubation on the gastric emptying rate of liquid in horses. ANIMALS: 6 healthy horses. PROCEDURES: Horses were assigned to treatment and control groups in a prospective randomized crossover study with a washout period of at least 4 weeks between trials. Acetaminophen (20 mg/kg) diluted in 1 L of distilled water was administered via nasogastric tube at time points of 0, 12, 30, 48, and 72 hours to evaluate the liquid-phase gastric emptying rate. In control horses, nasogastric tubes were removed after administration of acetaminophen. In horses receiving treatment, the tube was left indwelling and maintained for 72 hours. A 10-mL sample of blood was collected from a jugular vein immediately before and 20, 40, 60, 80, 100, 120, and 180 minutes after acetaminophen administration. Serum acetaminophen concentrations were measured by use of a colorimetric method. RESULTS: Peak serum acetaminophen concentration was significantly higher in the control group (38.11 microg/mL) than in the treatment group (29.09 microg/mL), and the time required to reach peak serum acetaminophen concentration was significantly shorter in the control group (22.79 minutes) than in the treatment group (35.95 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that indwelling nasogastric intubation has a delaying effect on the gastric emptying rate of liquids. Veterinarians should consider the potential for delayed gastric emptying when placing and maintaining an indwelling nasogastric tube for an extended period of time after surgery. Repeated nasogastric intubation may be better than maintenance of an indwelling tube in horses with ileus.     

Dynamics in serum of the inflammatory markers serum amyloid A (SAA), haptoglobin,fibrinogen and alpha2-globulins during induced noninfectious arthritis in the horse

Despite the importance of noninfectious joint diseases in equine medicine, little is known about the acute phase response which may be elicited if the local inflammatory process of noninfectious arthritis is sufficiently strong, Therefore the aim of this study was to monitor the systemic inflammatory response during experimentally-induced noninfectious arthritis by studying the dynamics in serum of the acute phase proteins serum amyloid A (SAA), haptoglobin, fibrinogen and alpha2-globulins. Twenty-four Standardbred horses, age 3-7 years, found healthy on thorough clinical, radiological, haematological and serum biochemical examination, were injected aseptically into the right midcarpal joint with amphotericin B. Blood samples were drawn before induction of arthritis (0 h), and at 8, 16, 24, 36 and 48 h postinduction and then on Days 3, 4, 5 and 15 postinduction. All horses developed lameness with joint effusion and joint heat as well as increased respiratory rate, heart rate and body temperature. The lameness started to decline after 24-36 h and, in most animals, systemic signs disappeared on Day 2 postinjection. The concentration of the acute phase proteins increased following induction of arthritis. The SAA concentrations were higher than baseline concentrations from 16 h postinduction and were maximal at 36-48 h (227 times baseline concentration). The haptoglobin concentrations were higher than baseline concentrations from 24 h and were maximal at 48-96 h (1.14 times baseline concentration). The maximal concentrations of fibrinogen were seen between 36-72 h postinjection and increased on average 0.87 times from baseline concentrations. The fibrinogen concentrations were higher than baseline concentrations from 24 h postinjection. Alpha2-globulins concentrations showed a minor increase and increased 0.55 times from baseline concentrations. The markers had returned to baseline concentrations by Day 15. Our results demonstrate that amphotericin B-induced arthritis in a single joint gives rise to a systemic acute phase response measurable as increased concentrations in serum SAA, haptoglobin, fibrinogen and alpha2-globulins during the first 2 weeks of the condition and, thereby, that such an increase need not be indicative of infectious arthritis. Further research should be aimed at determining whether chronic noninfectious arthritis in the horse gives rise to increased acute phase protein concentrations in serum.     

The acute phase response in calves experimentally infected with bovine viral diarrhoea virus and/or Mannheimia haemolytica

The aim of this investigation was to study differences and similarities in the acute phase response of calves experimentally infected in the respiratory tract with either bovine viral diarrhoea virus (BVDV) or Mannheima haemolytica (Mh), or with a combination of both (BVDV/Mh). A non-inoculated control group was also included. The acute phase response was measured by serum or plasma concentrations of the acute phase proteins (APPs) haptoglobin, serum amyloid A (SAA) and fibrinogen, and of cortisol, prostaglandin F2alpha-metabolite and interferon-alpha (IFN-alpha) activity. Clinical symptoms were also recorded and were most severe in the BVDV/Mh group. The symptoms were mild to moderate in the BVDV group, while none, or very mild symptoms were observed in the Mh group. In all inoculated groups, a significant acute phase response was observed, with elevated values of haptoglobin, SAA and fibrinogen, while the control group remained unaffected throughout the study. In general, the magnitude of the response was similar, but the duration of elevated concentrations of APPs was significantly longer in the BVDV/Mh group than in the BVDV group, reflecting the duration of the clinical symptoms. However, in the single infection groups, the APP response and the clinical symptoms were not correlated. The IFN-alpha activity increased in all BVDV-inoculated animals, but no response in cortisol and PGF2alpha-metabolite concentrations was observed after infection. Basal levels of serum concentrations of haptoglobin, SAA and fibrinogen were established and may be used for evaluating calf health in herds. The duration of elevated haptoglobin, SAA and fibrinogen values did not differ significantly within groups indicating that their value as indicator of disease is equal.     

Acute Phase Response to Surgery of Varying Intensity in Horses: A Preliminary Study

Objective— To evaluate the postoperative inflammatory response of horses to elective surgery of varying intensity.
Study Design— Prospective longitudinal study.
Animals— Horses referred to 2 hospitals for either arthroscopic removal of a unilateral osteochondritic lesion in the tibiotarsal joint (minimal surgical trauma, n=11), correction of recurrent laryngeal neuropathy by laryngoplasty and ventriculectomy (intermediate surgical trauma, n=10) or removal of an ovarian tumor by laparotomy (major surgical trauma, n=5).
Methods— Horses had a thorough clinical examination every day. White blood cell (WBC) counts and concentrations of serum amyloid A (SAA), fibrinogen, and iron were assessed in blood samples obtained before, and 1–3, 5, 7, 9, and 11 days after surgery. Differences in levels of the inflammatory markers between the 3 surgical groups were analyzed using repeated measures ANOVA.
Results— Postoperative concentrations of SAA and fibrinogen were significantly higher in horses that had laparotomy and ovariectomy than in horses that had laryngoplasty and ventriculectomy, or arthroscopy. Iron concentrations decreased to lower levels after intermediate and major surgical trauma than after small surgical trauma. WBC count did not differ between the 3 groups.
Conclusions— Levels of SAA, fibrinogen, and iron reflected the intensity of the surgical trauma, whereas WBC count did not.
Clinical Relevance— Postoperative measurements of SAA, fibrinogen, and iron may be useful for comparing surgical trauma associated with new and established surgical techniques. Moreover, knowledge of the normal postoperative acute phase response is essential, if acute phase reactants are to be used for monitoring occurrence of postoperative infections.     

Comparison of methods used to diagnose generalized inflammatory disease in manatees (Trichechus manatus latirostris).

Manatees (Trichechus manatus latirostris) are afflicted with inflammatory and infectious disease secondary to human interaction, such as boat strike and entanglement, as well as "cold stress syndrome" and pneumonia. White-blood-cell count and fever, primary indicators of systemic inflammation in most species, are insensitive in diagnosing inflammatory disease in manatees. Acute phase-response proteins, such as haptoglobin and serum amyloid A, have proven to be sensitive measures of inflammation/infection in domestic large animal species. This study assessed diagnosis of generalized inflammatory disease by different methods including total white-blood-cell count, albumin: globulin ratio, gel electrophoresis analysis, C-reactive protein, alpha, acid glycoprotein, haptoglobin, fibrinogen, and serum amyloid A. Samples were collected from 71 apparently healthy and 27 diseased animals during diagnostic medical examination. Serum amyloid A, measured by ELISA, followed by albumin:globulin ratio, measured by plasma gel electrophoresis, were most sensitive in diagnosing inflammatory disease, with diagnostic sensitivity and specificity of approximately 90%. The reference interval for serum amyloid A is <10-50 microg/ml with an equivocal interval of 51-70 microg/ml. The reference interval for albumin:globulin ratio by plasma gel electrophoresis is 0.7-1.1. Albumin: globulin ratio, calculated using biochemical techniques, was not accurate due to overestimation of albumin by bromcresol green dye-binding methodology. Albumin:globulin ratio, measured by serum gel electrophoresis, has a low sensitivity of 15% due to the lack of fibrinogen in the sample. Haptoglobin, measured by hemoglobin titration, had a reference interval of 0.4-2.4 mg/ml, a diagnostic sensitivity of 60%, and a diagnostic specificity of 93%. The haptoglobin assay is significantly affected by hemolysis. Fibrinogen, measured by heat precipitation, has a reference interval of 100-400 mg/dl, a diagnostic sensitivity of 40%, and a diagnostic specificity of 95%.     

Concentrations of gentamicin in serum and bronchial lavage fluid after once-daily aerosol administration to horses for seven days

OBJECTIVE: To assess gentamicin concentrations in serum and bronchial lavage fluid (BLF) of horses during a 24-hour period after once-daily aerosol administration of gentamicin (GAER) for 7 days and the pattern and degree of bronchial tree inflammation associated with repeated GAER. ANIMALS: 13 healthy adult horses (9 geldings and 4 mares). PROCEDURE: The treatment group comprised 8 horses, and 5 horses were untreated control animals. Gentamicin (20 mL of gentamicin [50 mg/mL]) was administered via aerosol once daily for 7 days. Samples of serum and BLF were obtained from all horses before GAER and 0.5, 4, 8, and 24 hours after the final day of GAER. Gentamicin concentrations were determined for all samples from treated horses, and cytologic examinations were performed on all BLF samples. RESULTS: Peak median BLF gentamicin concentration detected at 0.5 hours was 2.50 microg/mL. Median serum gentamicin concentration was < 0.50 microg/mL at all time points. Significant differences were not observed in total nucleated cell counts or differential cell counts in BLF between groups at any time point. Neutrophil count in BLF for all horses was increased over baseline at 4 and 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: We did not detect evidence of gentamicin accumulation or respiratory inflammation after once-daily GAER for 7 days. This protocol appears unlikely to result in local or systemic toxicosis. Repeated daily GAER to horses appears to be a safe procedure and may have clinical use in the treatment of horses with bacterial infections of the airways.     

Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions

The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were higher in the serum and milk of the cows with mastitis than in the cows in the other two groups. Four of the cows with extramammary inflammatory conditions had serum amyloid A concentrations in serum above 100 microg/ml, but negligible concentrations in milk, indicating that a pathogen must be present in the mammary gland for serum amyloid A to accumulate in milk. The acute phase protein concentrations in milk increased significantly with increasing somatic cell count, suggesting that they may be indicators of the severity of an infection.     

Hyaluronan in horses: physiological production rate, plasma and synovial fluid concentrations in control conditions and following sodium hyaluronate administration

REASONS FOR PERFORMING STUDY: Hyaluronic acid (HA) is an endogenous glycosaminoglycan used in the treatment of joint diseases, but medication control is required by horseracing authorities. Therefore, a medication control policy needs to be established. OBJECTIVES: To establish physiological plasma HA concentrations in post race horses, determine the HA endogenous production rate and document the disposition of HA after i.v. and intra-articular hyaluronic acid administration at recommended therapeutic doses. METHODS: Hyaluronan concentrations in plasma were determined using an ELISA specific test; concentrations in synovial fluid were determined using a radiometric binding assay. RESULTS: The overall mean plasma HA concentration in 120 post competition horses was 89 ng/ml. In a group of 6 experimental horses, synovial fluid control concentration was 328+/-112 microg/ml. After i.v. sodium hyaluronate administration (37.8 mg in toto), the terminal half-life was very short (43+/-29 mins) and after a delay of 3 h, the plasma concentration returned to control values. The endogenous HA production rate was 33-164 mg in toto per day, i.e. 1-4 times the recommended i.v. daily dose. Twenty-four hours after intra-articular administration, HA concentration was not significantly different from control values (328+/-112 microg/ml). CONCLUSIONS AND POTENTIAL RELEVANCE: Due to the rapid disappearance of HA from plasma after i.v. administration and from the joint after intra-articular administration, long-term detection needs a more appropriate approach to be developed.     

Serum iron and plasma fibrinogen concentrations as indicators of systemic inflammatory diseases in horses

BACKGROUND: Detection of systemic inflammation, which is important for proper diagnosis and prompt treatment, can be challenging. HYPOTHESIS: Measurement of plasma iron concentration is a sensitive method for detecting systemic inflammation in horses compared with measurements of plasma fibrinogen concentration, a traditional marker for inflammation in the horse. ANIMALS: Ninety-seven horses hospitalized with diseases causing systemic inflammation, 22 horses with localized inflammation, and 12 clinically normal horses were included in this study. METHODS: A retrospective study was made on hospitalized horses that had both plasma iron and fibrinogen concentrations measured on hospital admission. RESULTS: Plasma iron concentration was lower in horses with systemic inflammation (64 +/- 45 microg/dL) than the reference interval minimum (105 microg/dL) and were significantly lower (P = .001) than the value in a group of horses with local inflammation (123 +/- 45 microg/dL) and in healthy transported horses (143 +/- 29 microg/dL). Low plasma iron and high fibrinogen concentrations were both sensitive indicators of systemic inflammation in horses with sensitivity of 90 and 82%, respectively. There was a similar correlation between either continued decreases in iron concentration (Rsp of 0.239) or increases in fibrinogen concentration (Rsp of 0.280) during hospitalization and a worse prognosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of plasma iron concentration better reflected acute inflammation than did fibrinogen concentration.     

Systemic dexamethasone concentration in horses after continued topical treatment with an ophthalmic preparation of dexamethasone.

OBJECTIVE: To determine concentrations of dexamethasone in serum and urine of horses treated repeatedly with a topically administered ophthalmic dexamethasone preparation. ANIMALS: 4 clinically normal horses (2 mares, 2 geldings). PROCEDURE: 0.1% dexamethasone ophthalmic ointment was administered to the left eye of each horse every 5 to 9 hours for 8 consecutive days, yielding an estimated cumulative dexamethasone dose of 6.4 microg/kg of body weight. Serum and urine samples were obtained before the first dexamethasone treatment, on days 4 and 8 of treatment, and 24, 48, and 96 hours after cessation of treatment. To detect small concentrations of dexamethasone, serum and urine samples were analyzed by use of a competitive enzyme immunoassay. RESULTS: During the period of continued topical treatment, serum dexamethasone concentrations increased to between 0.10 and 0.49 ng/ml, then decreased below the limit of detection (0.06 ng/ml) within 24 hours after cessation of treatment. Dexamethasone also was detected in urine samples at concentrations of up to 0.98 ng/ml. CONCLUSIONS: Repeated topical administration of dexamethasone ophthalmic ointment generated low, but detectable glucocorticoid concentrations in serum and urine. CLINICAL RELEVANCE: Because treatment of performance horses with dexamethasone is prohibited for most types of competitions and because enhanced glucocorticoid detection methods may result in positive test results, owners and trainers may wish to reconsider entering horses in competitions during periods of treatment with ophthalmic dexamethasone preparations.     

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.     

Pharmacokinetics of flunixin meglumine in donkeys, mules, and horses

OBJECTIVE: To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. ANIMALS: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. PROCEDURE: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumine concentrations. The serum concentration-time curve for each horse, donkey, and mule were analyzed separately to estimate noncompartmental pharmacokinetic variables RESULTS: Mean (+/-SD) area under the curve for donkeys (646 +/- 148 minute x microg/ml) was significantly less than for horses (976 +/- 168 minute x microg/ml) or for mules (860 +/- 343 minute x microg/ml). Mean residence time for donkeys (54.6 +/- 7 minutes) was significantly less than for horses (110 +/- 24 minutes) or for mules (93 +/- 30 minutes). Mean total body clearance for donkeys (1.78 +/- 0.5 ml/kg/h) was significantly different from that for horses (1.14 +/- 0.18 ml/kg/h) but not from that for mules (1.4 +/- 0.5 ml/kg/h). Significant differences were not found between horses and mules for any pharmacokinetic variable. CONCLUSION AND CLINICAL RELEVANCE: Significant differences exist with regard to serum disposition of flunixin meglumine in donkeys, compared with that for horses and mules. Consequently, flunixin meglumine dosing regimens used in horses may be inappropriate for use in donkeys.     

In vitro dose-dependent effects of enrofloxacin on equine articular cartilage.

OBJECTIVE: To determine whether enrofloxacin has detrimental, dose-dependent effects on equine articular cartilage in vitro. ANIMALS: Cartilage explants were developed from 6 healthy horses between 0 and 96 months old. PROCEDURE: Patellar cartilage explants were incubated in 5 concentrations of enrofloxacin (2 microg/ml, 10 microg/ml, 1,000 microg/ml, 10,000 microg/ml, and 50,000 microg/ml) for 72 hours. Proteoglycan synthesis (Na35SO4 incorporation for 24 hours), proteoglycan degradation (Na35SO4 release for 72 hours), endogenous proteoglycan content (dimethylmethlene blue assay), and total protein content were determined. Cartilage explants were evaluated by use of histomorphologic and histomorphometric techniques (toluidine blue stain) for cytologic and matrix characteristics. Quantitative data were analyzed with a one-way ANOVA to compare results among various enrofloxacin concentration groups and the control group. A general linear model was used to determine whether age had an effect. RESULT: Proteoglycan synthesis was excellent in control specimens and in specimens incubated in low concentrations of enrofloxacin (2 microg/ml and 10 microg/ml). High concentrations of enrofloxacin (> 1,000 microg/ml) effectively eliminated proteoglycan synthesis regardless of horse age. Proteoglycan degradation at low concentrations (2 microg/ml and 10 microg/ml) was not different than control. High concentrations of enrofloxacin (> 1,000 microg/ml) caused significant degradation. Different concentrations of enrofloxacin did not affect endogenous proteoglycan. High concentrations of enrofloxacin were associated with a significant increase in number of pyknotic nuclei. CONCLUSION: Concentrations of enrofloxacin that might be achieved following systemic administration did not suppress chondrocyte metabolism in vitro. High concentrations of enrofloxacin (> 1,000 microg/ml) were toxic to chondrocytes.     

Pharmacokinetics of imipramine in narcoleptic horses

OBJECTIVE: To validate use of high-performance liquid chromatography (HPLC) in determining imipramine concentrations in equine serum and to determine pharmacokinetics of imipramine in narcoleptic horses. ANIMALS: 5 horses with adult-onset narcolepsy. PROCEDURE: Blood samples were collected before (time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration of imipramine hydrochloride (2 or 4 mg/kg of body weight). Serum was analyzed, using HPLC, to determine imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed separately to estimate pharmacokinetic values. RESULTS: Adverse effects (muscle fasciculations, tachycardia, hyperresponsiveness to sound, and hemolysis) were detected in most horses when serum imipramine concentrations were high, and these effects were most severe in horses receiving 4 mg of imipramine/kg. Residual adverse effects were not apparent. Value (mean +/- SD) for area under the curve was 3.9 +/- 0.7 h X microg/ml, whereas volume of distribution was 584 +/- 161.7 ml/kg, total body clearance was 522 +/- 102 ml/kg/h, and mean residence time was 1.8 +/- 0.6 hours. One horse had signs of narcolepsy 6 and 12 hours after imipramine administration; corrresponding serum imipramine concentrations were less than the therapeutic range. CONCLUSIONS AND CLINICAL RELEVANCE: Potentially serious adverse effects may be seen in horses administered doses of imipramine that exceed a dosage of 2 mg/kg. Total body clearance of imipramine in horses is slower than that in humans; thus, the interval between subsequent doses should be longer in horses.     

Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy

A randomized, controlled, blinded clinical trial was performed to determine whether butorphanol administered by continuous rate infusion (CRI) for 24 hours after abdominal surgery would decrease pain and surgical stress responses and improve recovery in horses. Thirty-one horses undergoing exploratory celiotomy for abdominal pain were randomly assigned to receive butorphanol CRI (13 microg/kg/h for 24 hours after surgery; treatment) or isotonic saline (control). All horses received flunixin meglumine (1.1 mg/kg IV q12h). There were no significant differences between treatment and control horses in preoperative or operative variables. Treatment horses had significantly lower plasma cortisol concentration compared with control horses at 2, 8, 12, 24, 36, and 48 hours after surgery. Mean weight loss while hospitalized was significantly less for treatment horses than control horses, whether expressed as total decrease in body weight (13.9+/-3.4 and 27.9+/-4.5 kg, respectively) or as a percentage decrease in body weight (2.6+/-0.7 and 6.3+/-1.1%, respectively). Treatment horses were significantly delayed in time to first passage of feces (median times of 15 and 4 hours, respectively). Treatment horses had significantly improved behavior scores during the first 24 hours after surgery, consistent with the conclusion that they experienced less pain during that time. Butorphanol CRI during the immediate postoperative period significantly decreased plasma cortisol concentrations and improved recovery characteristics in horses undergoing abdominal surgery.     

Acute exercise does not induce an acute phase response (APR) in Standardbred trotters

The purpose of the study was to investigate whether acute strenuous exercise (1600- to 2500-m race) would elicit an acute phase response (APR) in Standardbred trotters. Blood levels of several inflammatory markers [serum amyloid A (SAA), haptoglobin, fibrinogen, white blood cell count (WBC), and iron], muscle enzymes [creatinine kinase (CK) and aspartate transaminase (AST)], and hemoglobin were assessed in 58 Standardbred trotters before and after racing. Hemoglobin levels increased and iron levels decreased 12 to 14 h after racing and haptoglobin concentrations, white blood cell counts, and iron levels were decreased 2 and/or 7 d after racing. Concentrations of CK, AST, SAA, and fibrinogen were unaltered in response to racing.Acute strenuous exercise did not elicit an acute phase reaction. The observed acute increase in hemoglobin levels and decreases in haptoglobin and iron levels may have been caused by exercise-induced hemolysis, which indicates that horses might experience a condition similar to athlete’s anemia in humans. The pathogenesis and clinical implications of the hematological and blood-biochemical changes elicited by acute exercise in Standardbred trotters in the present study warrant further investigation.