Objective—To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa.
Sample—Gastric mucosa from 6 mature mixed-breed dogs.
Procedures—Sections of gastric mucosa were mounted in Ussing chambers, and carprofen (40 or 400μg/mL [CAR40 and CAR400, respectively]), meloxicam (8 or 80μg/mL [MEL8 and MEL80, respectively]), or no drug (controls) was added to the bathing solution. For all sections, conductance was calculated every 15 minutes for 240 minutes and flux of mannitol was calculated for 3 consecutive 1-hour periods; histologic examination was performed after the experiment. The area under the conductance-time curve for each chamber was calculated. Values of conductance × time, flux of mannitol, and the frequency distribution of histologic findings were analyzed for treatment effects.
Results—For CAR400- and MEL80-treated sections, conductance X time was significantly higher than that for control and MEL8-treated sections. The effect of CAR40 treatment was not different from that of any other treatment. Over the three 1-hour periods, mannitol flux increased significantly in MEL80-, CAR40-, and CAR400-treated sections but not in MEL8- treated or control sections. Major histologic changes including epithelial cell sloughing were limited to the CAR400-treated sections.
Conclusions and Clinical Relevance—In the gastric mucosa of dogs, carprofen and meloxicam increased in vitro conductance and permeability to mannitol. At a concentration of 400 μg/mL, carprofen caused sloughing of epithelial cells. Carprofen and meloxicam appear to compromise gastric mucosal integrity and barrier function in dogs.
Objective—To measure effects of carprofen on conductance and permeability to mannitol and histologic appearance in canine colonic mucosa.
Sample Population—Colonic mucosa from 13 mature mixed-breed dogs.
Procedures—Sections of mucosa from the transverse colon and proximal and distal portions of the descending colon were obtained immediately after dogs were euthanized. Sections were mounted in Ussing chambers. Carprofen (400 μg/mL) was added to the bathing solution for treated sections. Conductance was calculated at 15-minute intervals for 240 minutes. Flux of mannitol was calculated for three 1-hour periods. Histologic examination of sections was performed after experiments concluded. Conductance was graphed against time for each chamber, and area under each curve was calculated. Conductance × time, flux of mannitol, and frequency distribution of histologic findings were analyzed for an effect of region and carprofen.
Results—Carprofen significantly increased mean conductance × time, compared with values for control (untreated) sections for all regions of colon. Carprofen significantly increased mean flux of mannitol from period 1 to period 2 and from period 2 to period 3 for all regions of colon. Carprofen caused a significant proportion of sections to have severe sloughing of cells and erosions involving ≥ 10% of the epithelium, compared with control sections.
Conclusions and Clinical Relevance—Carprofen increased in vitro conductance and permeability to mannitol in canine colonic mucosa. Carprofen resulted in sloughing of cells and erosion of the colonic mucosa. These findings suggested that carprofen can compromise the integrity and barrier function of the colonic mucosa of dogs.
Objective—To determine pathophysiologic effects of phenylbutazone on the equine right dorsal colon (RDC).
Animals—12 healthy adult horses.
Procedures—A controlled crossover observational study was conducted. Clinical and serum variables, colonic inflammation (histologic grading), and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA) and prostaglandin E2 (PGE2) concentrations, ingesta volatile fatty acid (VFA) content, and arterial blood flow in the RDC were evaluated for a 21-day period in horses administered phenylbutazone (8.8 mg/kg, PO, q 24 h) or a control substance.
Results—Data from 8 horses were analyzed. Plasma albumin concentrations decreased significantly from days 10 to 21 during phenylbutazone treatment, compared with results during the same days for the control treatment. Phenylbutazone treatment caused neutropenia (< 3.0 × 103 cells/μL). No other clinical or hematologic abnormalities were detected for phenylbutazone or control treatments. Two horses developed colitis while receiving phenylbutazone. No significant differences were detected in the RDC between phenylbutazone and control treatments for MPO activity, MDA and PGE2 concentrations, and histologic evidence of inflammation. Arterial blood flow in the RDC was significantly increased during phenylbutazone treatment, compared with values for the control treatment. Differences were identified in VFA production during phenylbutazone treatment, compared with the control treatment, with a decrease in acetic acid concentrations over time.
Conclusions and Clinical Relevance—Prolonged phenylbutazone administration caused hypoalbuminemia, neutropenia, changes in RDC arterial blood flow, and changes in VFA production. Veterinarians should monitor serum albumin concentrations and neutrophil counts and be cautious when making dosing recommendations for phenylbutazone treatment of horses.
Objective—To evaluate chondrocyte death in canine articular cartilage exposed in vitro to bupivacaine with and without methylparaben and to compare viability for cartilage with intact or mechanically debrided surfaces.
Sample Population—Both glenohumeral joints from 10 adult canine cadavers.
Procedures—10 osteochondral cores were harvested from each of the 20 humeral heads; synovium and 1 core from each joint were examined to verify joint health, and the other 9 cores were exposed to canine chondrocyte culture medium (CCCM), a 0.5% solution of bupivacaine, or 0.5% solution of bupivacaine with methylparaben for 5, 15, or 30 minutes.
Results—For the superficial zone of surface-intact chondrocytes, bupivacaine with methylparaben caused a significantly higher percentage of chondrocyte death at 5 minutes (47.7%) than did bupivacaine (23.6%) or CCCM (25.4%). Bupivacaine (53.8%) and bupivacaine with methylparaben (62.5%) caused a significantly higher percentage of chondrocyte death at 30 minutes than did CCCM (20.0%). For the superficial zone of chondrocytes with debrided surfaces, bupivacaine with methylparaben caused a significantly higher percentage of chondrocyte death at 30 minutes (59%) than it did at 5 minutes (37.7%). Bupivacaine with methylparaben caused a significantly higher percentage of chondrocyte death at 30 minutes (59.0%) than did CCCM (28.9%). For middle and deep zones of chondrocytes, treatment solution and surface debridement had minimal effects on percentage of chondrocyte death.
Conclusions and Clinical Relevance—Bupivacaine and bupivacaine with methylparaben were cytotoxic to canine articular chondrocytes in vitro. Intra-articular administration of bupivacaine is not recommended for clinical use until additional studies are conducted.
Case Description—3 Quarter Horse racehorses were examined for suspected clenbuterol overdose 12 to 24 hours after administration by mouth of a compounded clenbuterol product.
Clinical Findings—All horses developed sinus tachycardia, muscle tremors, hyperhidrosis, and colic. Abnormalities on serum biochemical analysis included hyperglycemia, azotemia, and high creatine kinase activity. The presence of clenbuterol in the serum of all 3 horses and in the product administered was confirmed and quantified by use of liquid chromatography-electrospray tandem mass spectrometry.
Treatment and Outcome—Propranolol (0.01 mg/kg [0.005 mg/lb], IV) was administered to all 3 horses for antagonism of β-adrenergic effects and caused a transient decrease in heart rate in all patients. All horses also received crystalloid fluids IV and other supportive treatment measures. Two horses were euthanatized (2 and 4 days after admission) because of complications. One horse recovered and was discharged 4 days after admission to the hospital. In the 2 nonsurviving horses, skeletal and cardiac muscle necrosis was evident at necropsy, and tissue clenbuterol concentrations were highest in the liver.
Clinical Relevance—Clenbuterol is a β2-adrenergic receptor agonist licensed for veterinary use as a bronchodilator. At doses ≥ 10 2μg/kg (4.5 μg/lb), in excess of those normally prescribed, β-adrenergic stimulation by clenbuterol may cause sustained tachycardia, muscle tremors, hyperglycemia, and cardiac and skeletal muscle necrosis. Laminitis, acute renal failure, rhabdomyolysis, and cardiomyopathy were fatal complications associated with clenbuterol overdose in 2 horses in the present report. At the dose administered, propranolol was effective for short-term control of sinus tachycardia, but it did not alleviate all clinical signs in patients in the present report. These cases demonstrated the risks associated with the use of nonprescribed compounded medications for which the ingredients may be unknown.