title: Regadenoson, a novel pharmacologic stress agent for use in myocardial perfusion imaging, does not have a direct effect on the QT interval in conscious dogs.
abstract: Our goal was to determine the effect of regadenoson (a novel A2A adenosine receptor agonist) on the QT interval in conscious dogs. Sixteen mongrel dogs were chronically instrumented for measurements of blood pressure and ECG. Regadenoson (2.5, 5, and 10 microg/kg, IV) caused a dose-dependent QT interval shortening (DeltaQT: 14 +/- 3, 24 +/- 5, and 27 +/- 5 ms, mean +/- SEM; n = 7 to 11; all P < 0.05) associated with significant increases in HR (Peak HR: 114 +/- 9, 125 +/- 6, and 144 +/- 7 bpm). Atrial pacing (135, 150, and 165 bpm) also caused a frequency-dependent shortening of the QT interval (DeltaQT: 15 +/- 3, 22 +/- 3, and 39 +/- 5 ms; n = 6 to 7; all P < 0.05). Regadenoson- and pacing-induced shortenings in the QT interval were significantly correlated with the R-R interval (r = 0.67 and 0.8, both P < 0.05). Regadenoson at 5 and 10 microg/kg did not cause a significant change in HR or QT interval either during atrial pacing at 165 bpm or after administration of propranolol and atropine to prevent HR from changing or after treatment of dogs with hexamethonium to block autonomic ganglia. Regadenoson (5 to 10 microg/kg) caused no significant changes of QT interval in the heart in which HR was kept constant via physiological or pharmacological procedures, indicating that regadenoson has no direct effect on the QT interval.
authors.affiliation: Department of Pharmacology, CV Therapeutics, Inc., Palo Alto, California 94304, USA. gong.zhao@cvt.com
authors.forename: Gong
authors.initials: G
authors.lastname: Zhao
authors.forename: Sabrina
authors.initials: S
authors.lastname: Serpllion
authors.forename: John
authors.initials: J
authors.lastname: Shryock
authors.forename: Eric
authors.initials: E
authors.lastname: Messina
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Xu
authors.forename: Manuel
authors.initials: M
authors.lastname: Ochoa
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hintze
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005080:Exercise Test / Q000379:methods; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D055414:Myocardial Perfusion Imaging / Q000379:methods; D011687:Purines / Q000009:adverse effects* / Q000494:pharmacology; D011720:Pyrazoles / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D011687:Purines; D011720:Pyrazoles; C430916:regadenoson