Heart Rate-Specific Reference Ranges for Qt-Interval in Beagle Dogs

Abstract

In toxicity studies, the ECG is recorded over a range of escalating doses and the assessment of QT prolongation is made by comparing treated to untreated animals. As the QT interval and heart rate are inversely related, any imbalance in the distribution of heart rate across groups may bias this comparison. To avoid that risk, a formula for correcting QT intervals for heart rate is derived from the fit of a power model with random coefficients to historical controls. The correction and heart rate-specific reference ranges for QT are then used to refine the toxicity evaluation. The factor for dogs (1/5) is smaller than those used in humans (Bazett: 1/2; Fridericia: 1/3). This suggests that species-specific correction factors should be used to avoid misleading conclusions on QT prolongation.