Heart rate correction of the QT duration in rats.

Abstract Duration of heart rate corrected QT interval (QTc) is a crucial and critical factor in the assessment of repolarization changes considering safety of drugs and cardiac disorders. In rats, a validated approach to QT correction is lacking. In this study, we tested the normalization of QTc using normalization factor according to rat's cardiac cycle length (RR). Standard 12-lead ECG was measured in anesthetized rats at basal conditions and at various pharmacological conditions such as beta-adrenergic stimulation with isoproterenol or medication with clarithromycin (single- or repeated dosing for seven days), bisoprolol or ivabradine. For QT correction, standard Bazett's formula (QTc-B = QT / (RR) 1/2 ) and Bazett's formula normalized to average rat RR (QTc n -B = QT / (RR /  f ) 1/2 , f  = 150 ms) were compared. Duration of QT showed a positive correlation with RR duration (Pearson r  = 0.7645, P n -B were in the physiological range. QTc n -B was unrelated to RR (Pearson r  = 0.1122, not significant) but the relationship between QTc n -B and QT remained preserved (Pearson r  = 0.7216, P n -B was used. Beta-adrenergic stimulation with isoproterenol prolonged, while beta-blockade with bisoprolol shortened QTc n -B. Ivabradine dose-dependently induced bradycardia without altering QT. However, QTc n -B showed false positive shortening at sustained bradycardia. Therefore, adjusted formula for QTc n -B is suitable for QT correction in rats but its use should be considered carefully in case of very low heart rate.