Objective—To examine the secretory response (in
the presence and absence of prostaglandin inhibition)
in vitro and structural alterations of colonic mucosa in
horses after intragastric administration of black walnut
Animals—14 adult horses.
Procedure—Seven horses were administered
BWE intragastrically and monitored for 11 hours.
Tissue samples were obtained from the right ventral,
left ventral, and right dorsal colons (RVC, LVC,
and RDC, respectively) of the 7 BWE-treated and 7
control horses. Tissue samples were examined via
light microscopy, and the extent of hemorrhage,
edema, and granulocytic cellular infiltration (neutrophils
and eosinophils) was graded. Colonic
mucosal segments were incubated with or without
flunixin meglumine (FLM) for 240 minutes; spontaneous
electrical potential difference and short-circuit
current (Isc) were recorded and used to calculate
Results—Colonic tissues from BWE-treated horses
(with or without FLM exposure) had an overall greater
Isc during the 240-minute incubation period, compared
with tissues from control horses. The resistance
pattern in RVC, LVC, and RDC samples (with or
without FLM exposure) from BWE-treated horses
was decreased overall, compared with control tissues
(with or without FLM exposure). Histologically,
colonic mucosal tissues from BWE-treated horses
had more severe inflammation (involving primarily
eosinophils), edema, and hemorrhage, compared
with tissue from control horses.
Conclusions and Clinical Relevance—In horses,
BWE administration appears to cause an inflammatory
response in colonic mucosal epithelium that results
in mucosal barrier compromise as indicated by
decreased mucosal resistance with presumed concomitant
electrogenic chloride secretory response,
which is not associated with prostaglandin mediation.
(Am J Vet Res 2005;66:443–449)
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 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 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 determine the effects of clenbuterol, at a dosage of up to 3.2 μg/kg for 14 days, PO, on skeletal and cardiac muscle in healthy horses undergoing treadmill exercise.
Animals—12 healthy horses from 3 to 10 years old.
Procedures—Horses were randomly assigned to a control group (n = 6) or clenbuterol group (6) and received either saline (0.9% NaCl) solution or clenbuterol, PO, every 12 hours for 14 days. Horses were subjected to submaximal treadmill exercise daily during treatment. Muscle biopsy specimens were collected before and after treatment for determination of apoptosis. Echocardiographic measurements, serum clenbuterol and cardiac troponin I concentrations, and serum activities of creatine kinase and aspartate aminotransferase were measured before, during, and after treatment. Jugular venous blood samples were collected every 3 days during treatment. Echocardiography was repeated every 7 days after beginning treatment. Response variables were compared between treatment groups and across time periods.
Results—No significant effect of clenbuterol or exercise on response variables was found between treatment and control groups at any time point or within groups over time.
Conclusions and Clinical Relevance—Results did not reveal any adverse effects of treatment with an approved dose of clenbuterol on equine cardiac or skeletal muscle in the small number of horses tested.
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.