Assessment of ECG interval and restitution parameters in the canine model of short QT syndrome.
BACKGROUND
The short QT syndrome (SQTS) is characterized by a short QT interval resulting from accelerated ventricular repolarization, and may be associated with ventricular fibrillation but not torsades de pointes. There are abundant data on the adverse effects of long QT, but knowledge of SQTS is sparse. The aim of this study was to examine whether analyses of several ECG biomarkers (QT, QTcB, QTcF, QTcV, QT(btb), and QT(RR1000)) and dynamic restitution of the beat-to-beat QT-TQ relationship (TQ(min), %QT/TQ ratio>1, QT/TQ ratio(max)) can be used to assess ECG changes in conscious dogs.


METHODS
Sling-trained dogs were infused with escalating concentration of levcromakalim (0, 1.0, 3.3, and 10.0 microg/kg/min), pinacidil (0, 3.3, 10.0, and 33.3 microg/kg/min), and nicorandil (0, 0.03, 0.1, and 0.3 mg/kg/min), drugs known to shorten QT. The RR, QT, QTcB, QTcF, QTcV, QT(RR1000), and TQ were measured before and after each concentration of the QT shortening test compounds.


RESULTS
Levcromakalim, pinacidil, and nicorandil but not vehicle significantly shortened RR, QT, QT(btb), QT(RR1000), and TQ but not QTc(B,F,V). The QT-RR cloud also shifted to the lower bounds of the normal QT-RR boundary by the test compounds. The percentage of beats with a QT/TQ ratio>1 was significantly increased in a dose response manner with levcromakalim and pinacidil and the lower TQ interval boundary (5th percentile) was decreased when compared to baseline or vehicle.


CONCLUSIONS
QT(btb), QT(RR1000), and dynamic beat-to-beat measurements of restitution constitute clinically applicable ECG biomarkers for assessment of changes associated with arrhythmogenic risk of ventricular fibrillation due to QT abbreviation.
QTest Labs, LLC., 6438 Fiesta Dr, Columbus, OH 43235, USA.
Anusak
A
Kijtawornrat
Yaowalak
Y
Panyasing
Carlos
C
Del Rio
Robert L
RL
Hamlin
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D019806:Cromakalim / Q000633:toxicity; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D013577:Syndrome; D013997:Time Factors
D019806:Cromakalim