Signalment:  

3-year-old, gelding, quarter horse, (Equus caballus) equineThe patient presented with muscle fasciculations, hyperhidrosis, tachycardia (88 bpm) and tachypnea. The temperature was within normal limits and capillary refill time was prolonged. ECG revealed sinus tachycardia. Laboratory abnormalities included mild thrombocytopenia, azotemia (creatine 4.8), hyperglycemia (glucose 483), hypokalemia (K 3.0), hyponatremia (Na 120), hypochloremia (Cl 81), hyperbilirubinemia (4.6) and elevated CK (5050) and AST (927).


Gross Description:  

An adult quarter horse gelding (500 kg) in good flesh with mild postmortem autolysis is presented for necropsy. The cranioventral lungs, representing approximately 20% of the lung parenchyma, are sharply demarcated, dark green, and consolidated with marked expansion of the interlobular spaces by edema and yellow friable material (fibrin). The trachea and bronchial airways are filled with white foam; clear fluid oozes from the cut section. The remaining lung tissue is rubbery and partially collapsed. The cranioventral pulmonary pleura is covered by a thin layer of brown friable material (fibrin). The pericardial sac contains ~ 200 mls of dark yellow fluid. There is pale tan streaking throughout the myocardium of the ventricular free wall and the interventricular septum; the left ventricular free wall appears most severely affected. This discoloration affects greater than 40% of the myocardium. The liver is mildly firm and has an accentuated lobular pattern. There are several dozen subcapsular hemorrhages in both kidneys. Approximately 40% of the glandular stomach is thickened and hyperemic; about half of this area is covered by a fibrinous pseudomembrane. The stomach contains grain and hay/grass ingesta. The small colon contains formed feces. Urine is clear and yellow. There is mild edema of the lamina of P3 in the right front and left rear feet.


Histopathologic Description:

Heart: Multifocal myocardial degeneration and necrosis are present within multiple sections of heart, affecting approximately 25% of the myocardium. The change is characterized by loss of myocardial cross striations, fragmentation, and vacuolation of myocardial cytoplasm, and nuclear pyknosis and karyolysis (Fig. 1-1). Sarcolemmal sheaths are collapsed, satellite cell nuclei are plump and closely arranged, and there are moderate numbers of macrophages with fewer lymphocytes and occasional neutrophils in the affected areas. Perivascular supporting tissues and tissues surrounding Purkinje cells are expanded by edema fluid or finely granular, basophilic, loose mucinous material.


Morphologic Diagnosis:  

Heart: Myocardial degeneration and necrosis, severe, multifocal to coalescing, subacute, quarter horse, Equus caballus


Lab Results:  


Mild thrombocytopenia
Azotemia (creatinine 4.8)
Hyperglycemia (glucose 483)
Hypokalemia (K 3.0)
Hyponatremia (Na 120)
Hypochloremia (Cl 81)
Hyperbilirubinemia (4.6)
Elevated CK (5070)
Elevated AST (927)


Condition:  

Clenbuterol toxicosis


Contributor Comment:  

This horse is one of several that died or were euthanized after being given clenbuterol. In addition to the myocardial necrosis, the horse had varying degrees of skeletal muscle necrosis in different muscle groups. High levels of clenbuterol were found in this horses serum the day after dosing, and clenbuterol overdose is believed to be responsible for the clinical signs of muscle fasciculation, tachycardia, and hyperhydrosis seen at presentation, as well as for the skeletal and cardiac muscle degeneration and necrosis seen grossly and histologically.

Clenbuterol is a beta-2 sympathomimetic, with most of the pharmacologic activity coming from the levo form.4 The drug is used as a bronchodilator in horses and non-lactating cattle at a recommended dosage of 0.8 micrograms per kilogram of body weight.4 Excretion is primarily via urine as unmetabolized clenbuterol. Four studies have shown that clenbuterol induces myocardial necrosis in laboratory rats 1, 2, although a recent study of the relative myotoxicity of clenbuterol versus other beta agonists showed that clenbuterol is less myotoxic than fenoterol, another beta-2 sympathomimetic.3

In this case, further history revealed a questionable source of clenbuterol that, when tested at the LSU Analytical Systems Laboratory, contained 67.4 times the FDA approved level of the drug. The bottle was labeled Clenbuterol HCl, 72.5 mcg/ml, 0.5 ml/100lb, but actually contained 5.0 mg/ml instead of the labeled 72.5 mcg/ml, or 0.0725 mg/ml. The horse was given clenbuterol from this bottle five days prior to euthanasia.


JPC Diagnosis:  

Heart, left ventricle: Myocardial degeneration and necrosis, multifocally extensive, moderate, with histiocytic and lymphocytic myocarditis and fibroplasia


Conference Comment:  

Catecholamines and catecholamine receptor agonists are believed to cause myocardial necrosis in various settings including brain-heart syndrome, pheochromocytoma and sympathomimetic drug overdoses. Numerous toxins cause myocardial necrosis as well.

Ionophore toxicity occurs in horses and other monogastrics that are mistakenly fed coccidiostats used in ruminant and poultry feed.4

Cardiac glycosides are found in several different plants in various parts of the world, and ingestion often causes death within a few hours with little to no gross or histologic footprint.4These glycosides inhibit the sodium-potassium ATPase pump causing a disruption in ion concentration and membrane potential leading to muscle necrosis.4 Diagnosis is often based on discovery of the offending plant in the gastrointestinal system or circumstantial evidence.4

Some toxic alcohols, such as gossypol and tremetol, can cause myocardial necrosis. Gossypol, often found in cottonseed meal used as a protein supplement in feed, causes myocardial necrosis in young ruminants, pigs, and dogs.4 Tremetol is the toxic principal in Eupatorium rugosum (white snakeroot).4

Horses ingest blister beetles in dried hay, and the canthardin present in the insects causes gastric lesions, hemorrhagic cystitis, enterocolitis, and myocardial necrosis.4 Hairy vetch (Vicia villosa) can also cause myocardial lesions in cattle but not horses. Histologic lesions consist of monocytes, lymphocytes, plasma cells, and giant cells. In cattle, eosinophils are also present.5


References:

1. Burniston JG, Chester N, Clark WA, Tan LB, Goldspink DF: Dose-dependent apoptotic and necrotic myocyte death induced by the beta2-adrenergic receptor agonist, clenbuterol. Muscle Nerve 32:767-774, 2005
2. Burniston JG, Ng Y, Clark WA, Colyer J, Tan LB, Goldspink DF: Myotoxic effects of clenbuterol in the rat heart and soleus muscle. J Appl Physiol 93:1824-1832, 2002
3. Burniston JG, Tan LB, Goldspink DF: Relative myotoxic and haemodynamic effects of the betaagonists fenoterol and clenbuterol measured in conscious unrestrained rats. Exp Physiol 91:1041-1049, 2006
4. EMEA: Clenbuterol Hyodrochloride Summary Report (1), ed. Products CfVM. European Agency for the Evaluation of Medicinal Products, Veterinary Medicines and Information Technology Unit, 2000
5. Ginn, PE, Mansell JEKL, Rakich PM: Skin and appendages. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, vol. 1 ed. Maxie MG, pp. 619-620. Elsevier Limited, Philadelphia, PA, 2007
6. Maxie MG, Robinson WF: Cardiovascular system. In: Jubb, Kennedy and Palmers Pathology of Domestic Animals, vol. 3 ed. Maxie MG, 5th ed., pp. 32-33. Elsevier, Philadelphia, PA, 20073. Burniston JG, Tan LB, Goldspink DF: Relative myotoxic and haemodynamic effects of the betaagonists fenoterol and clenbuterol measured in conscious unrestrained rats. Exp Physiol 91:1041-1049, 2006


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1-1. Myocardium, horse.



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