Title page for ETD etd-07092009-163446


Type of Document Master's Thesis
Author Thompson, Jessica
URN etd-07092009-163446
Title Effects of Clenbuterol on Equine Skeletal and Cardiac Muscle
Degree Master of Science (M.S.)
Department Veterinary Clinical Sciences
Advisory Committee
Advisor Name Title
Rebecca S. McConnico Committee Chair
Daniel B. Paulsen Committee Member
Susan C. Eades Committee Member
Keywords
  • cardiac troponin I
  • echocardiogram
  • apoptosis
  • beta-adrenergic agonist
  • myopathy
  • horse
  • clenbuterol
Date of Defense 2009-06-17
Availability unrestricted
Abstract
Clenbuterol is a commonly prescribed β2-adrenergic agonist approved for veterinary use as a bronchodilator in horses with reactive and obstructive airway disease. Potential for abuse of this drug in the horse industry is substantial, due to the perceptions that clenbuterol increases performance and lean muscle mass. Although anabolic effects have been confirmed in multiple species, recent studies into the effects of clenbuterol in exercising horses suggest that clenbuterol doses within therapeutic ranges negatively impact aerobic capacity and cardiac function. Results of studies in murine models demonstrate that clenbuterol directly induces skeletal and cardiac muscle cell death at high doses.

Three cases of equine clenbuterol overdose are described, in which clinical signs of toxicity included tachycardia, muscle tremors, sweating and colic. Major laboratory abnormalities included hyperglycemia, azotemia and elevated creatine kinase activity. Two horses were euthanized due to complications of toxicity. Post-mortem abnormalities included skeletal and cardiac muscle necrosis.

The experimental study reported here examined the effects of oral clenbuterol on skeletal and cardiac muscle in clinically healthy horses undergoing treadmill exercise, as compared with a control group. Additionally, serum clenbuterol concentrations were measured throughout the treatment period.

This study was approved by the Louisiana State University Institutional Animal Care and Use Committee. Twelve clinically healthy Thoroughbred horses between the ages of 3 and 10 years old were randomly assigned to either the control group (n=6) or the clenbuterol group (n=6). Animals in the control group received saline by mouth twice daily for 14 days. Horses in the clenbuterol group received clenbuterol by mouth twice daily for 14 days, at incrementally increasing doses up to 3.2µg/kg. Horses were subjected to daily submaximal treadmill exercise during the treatment period. Muscle biopsies were collected before and after treatment for determination of apoptosis and histologic evidence of muscle damage. Echocardiographic measurements, serum clenbuterol concentration, and serum activities of creatine kinase, aspartate aminotransferase and cardiac troponin I were measured before, during, and after treatment. Venous blood samples were collected from the jugular vein(s) every 3 days during treatment. Echocardiography was repeated every 7 days after beginning treatment.

Serum biochemical and echocardiographic response variables were summarized as median and range. These variables were compared between treatment groups and across time periods using a Mann-Whitney U test and Friedman’s test for repeated nonparametric data, respectively. An adjusted level of significance at p<0.01 was used to reduce type I error. The presence of apoptosis in muscle biopsy samples was compared using a Cochran-Mantel-Haenszel stratified analysis, with a significance level of p<0.05. Serum clenbuterol concentrations and percent apoptosis were summarized as mean ± standard deviation.

No significant effect of clenbuterol or exercise on response variables was found between treatment and control groups at any time point, nor within groups over time. Clenbuterol was detected in the serum of all clenbuterol group horses during the treatment period. This study did not demonstrate any adverse effects of a 2-week course of clenbuterol treatment on equine cardiac or skeletal muscle at approved doses for treatment in horses.

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