QT interval measurement in the dog: chest leads versus limb leads.
BACKGROUND
An accurate measurement of the QT interval is dependent on the accurate identification of the end of the T wave. Although chest leads have been recommended in dog toxicology studies, their use has not been widely put into practice, as shown by a recent survey on methodology for ECG collection in the pharmaceutical industry. Therefore, there is little published data on dog QT measurement from chest leads.


METHODS
Electrocardiograms (ECGs) were taken from 100 beagle dogs (50 males, 50 females), with the dogs restrained in a sling. On the day of recording, measurements were performed at time zero and 1 h later. Recordings were repeated 7 to 10 days later. QT interval measurements were taken simultaneously from Lead II and the chest Lead CV5RL. Heart rate was taken from Lead II. Statistical analyses included the calculation of a QT correction formula, comparison of the mean values and variability of QT and QTc measurements from Leads II and CV5RL, the comparison of T-wave polarity from both leads, and a power analysis for QT and QTc.


RESULTS
The T wave was positive in almost all dogs (99/100) in the Lead CV5RL at all measurement periods, while it was either positive or negative in Lead II (64-75/100), and the incidence of positive T wave varied between measurement periods. The QT interval was significantly shorter (194+/-11 to 197+/-12 vs. 197+/-13 to 200+/-12 ms) when measured from the CV5RL lead at all recording periods and in both sexes. In addition, the standard deviation for QT measurement within each individual ECG record demonstrates less intra-animal variation when QT is measured from Lead CV5RL compared with Lead II (3.8 vs. 13.2 ms). The linear regression between QT and heart rate was improved when QT measurements were taken from CV5RL, as shown by the percentage of variability R2.


CONCLUSIONS
Estimates of the sample sizes showed that fewer animals would be required to detect a change at both the high and the mid-doses when using the chest Lead CV5RL. Using Lead II, we are able to detect within-animal changes of 10% in either QT or QTc; with Lead CV5RL, we are able to detect 10% change in QT and 5% change in QTc.
Nahas
Kamil
K
Amboise Laboratories, Pfizer Inc. Global Research and Development-safety Science Europe, B.P. 159, Amboise 37401, France. Kamil.nahas@pfizer.com
Geffray
Brigitte
B
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000295:instrumentation* / Q000662:veterinary*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D007756:Laboratory Animal Science / Q000379:methods*; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000662:veterinary*; D008297:Male; D013909:Thorax; D018675:Toxicity Tests; D015262:Xenobiotics / Q000494:pharmacology
D015262:Xenobiotics