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The Utility of the Small Rodent Electrocardiogram in Toxicology
Citation:
FARRAJ, A., M. S. HAZARI, AND W. E. Cascio. The Utility of the Small Rodent Electrocardiogram in Toxicology. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 1(1):11-30, (2011).
Impact/Purpose:
Thousands of agents have cardiotoxic effects. The electrocardiogram is a sensitive measure of cardiotoxicity. Because rats and mice are the predominant species used in toxicological studies and a review of the utility of the ECG in these species in toxicology has not been examined in decades, it is important to provide an up-to-date review of the utility of the small rodent ECG in toxicology.
Description:
Extensive research has lead to a growing appreciation that the heart is acutely sensitive to a broad array of toxicants via multiple routes of exposure. These agents are as diverse as the anti-neoplastic drug doxorubicin and various components of ambient air pollution. Adverse effects in the heart often manifest as a change in the electrocardiogram (ECG). The ECG has long been used in the clinic to assess human cardiovascular health. Surface electrocardiographic recordings (i.e., those made from the skin) in humans often help detect abnormal myocardial impulse formation, conduction, cardiac rhythm disturbances, and altered autonomic regulation of the heart. In toxicology, the ECG provides a collection of endpoints that may be used to assess both the quality and magnitude of cardiac toxicity. The most recent review of the utility of ECG measurements in toxicological studies was published in 1997 and described assessments in multiple species based on methodologies that relied on anesthesia or physical restraint, which have now been replaced by modem non-invasive techniques in conscious animals. While the dog is the primary model used to assess ECG affects in the pharmaceutical industry, rats and mice are the most common species used in general toxicological studies and there is increasing interest in the incorporation of ECG assessments in small rodent studies to assess cardiotoxicity. This review will discuss the utility of the small rodent ECG, various methodologies used to derive ECG data in rats and mice, and ways to incorporate ECG measurements and analysis in small rodent toxicology studies.
