Non-drug-related electrocardiographic features in animal models in safety pharmacology

No study of a test article is complete without attempting to determine its risk for production of toxicity to all important components of cardiovascular function (e.g., electrophysiological, mechanical, biochemical, baroreceptor). Electrocardiography is extremely useful for interrogating important electrophysiological properties: chronotropy (heart rate), dromotropy (conduction through the atria and ventricles, and through atrioventricular conduction), and predilection to produce arrhythmia, in particular, torsade de pointes. However, there are many factors that make electrocardiography less than optimal for detecting potential toxicological effects in studies of safety pharmacology. This paper will present examples of common difficulties in recording or in interpreting electrocardiograms, specifically due to artifacts in ECGs produced by the methods of electrocardiography, and by the “unusual” electrophysiology of the species/subject. One of the most contentious issues in electrocardiology is correction of QT for heart rate (Malik, M. (2001). Problems of heart rate correction in assessment of drug-induced QT interval prolongation. Journal of Cardiovascular Electrophysiology, 12, 411-420). This will not be discussed.