Species differences in metabolism, tissue localization, specificity and sensitivity for cardiac damage influence the choice of biochemical investigation used in the assessment of cardiotoxicity. The tests currently used in toxicological studies are broadly categorized herein as enzymes and other proteins, lipids and electrolytes; some limitations of these tests are also discussed. * This paper has been prepared on behalf of, and reviewed by, the membership of the Animal Clinical Chemistry Association of the UK. The opinions expressed are a consensus view, and do not necessarily represent the views of any individual member. t Author t o whom correspondence should be addressed.
ment. Drugs for the treatment of cardiovascular disease may be used over a long period, e.g. hypolipidemics and hypertensives, while others for much shorter periods, e.g. thrombolytic agents. Many reviewers of cardiotoxicity have emphasized the importance of histopathology and electrocardiography for diagnosis. Lesser emphasis has been given to clinical chemistry measurements, as biochemical and functional changes may not be detected during early stages of cardiotoxicity, although there is histological evidence at necropsy.
Since both toxicological and pharmacological responses vary between species, the choice of an appropriate animal is not always obvious. It has been suggested that some common laboratory species, e.g. rat and mouse, are not completely satisfactory for studies of drug-induced cardiomyopathies. Other less commonly used species, such as the turkey poult, have been proposed as alternatives3 but even in this species, enzyme changes were demonstrated more readily in cardiac tissue than blood following the administration of the growth promotor furazolidone.4 Obesity, diet. genetic variation, anaemia, thyroid status, poor nutritional status and age may all be contributing factors to cardiotoxicity, e.g. the cardiotoxic effects of cobalt given to rats increase with age, protein and thiamine deficiency.
Occasionally, animal models of cardiac disease are used in determining paradoxical cardiac effects caused by some drugs, e.g. bronchodilators: in these investigations, it is essential to establish baseline data. Consideration also must be given to possible drug interactions that may cause cardiotoxicity, e.g. the administration of diuretics can cause excessive losses of potassium and magnesium and these losses then potentiate the cardiac effects of digitalis.
Urine tests are generally not helpful in detecting