Electrophysiologic effects of a novel selective adenosine A1 agonist (CVT-510) on atrioventricular nodal conduction in humans.
BACKGROUND
CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, is a selective A(1)-adenosine receptor agonist with potential potent antiarrhythmic effects in tachycardias involving the atrioventricular (AV) node. This study, the first in humans, was designed to determine the effects of CVT-510 on AV nodal conduction and hemodynamics.


RESULTS
Patients in sinus rhythm with normal AV nodal function at electrophysiologic study (n = 32) received a single intravenous bolus of CVT-510. AH and HV intervals were measured during sinus rhythm and during atrial pacing at 1, 5, 10, 15, 20, 30, 45, and 60 minutes after the bolus. Increasing doses of CVT-510 (0.3 to 10 microg/kg) caused a dose-dependent increase in the AH interval. At 1 minute, a dose of 10 microg/kg increased the AH interval during sinus rhythm from 93 +/- 23 msec to 114 +/- 37 msec, p = 0.01 and from 114 +/- 31 msec to 146 +/- 44 msec during atrial pacing at 600 msec, p = 0.003). The AH interval returned to baseline by 20 minutes. CVT-510 at doses of 0.3 to 10 microg/kg had no effect on sinus rate, HV interval, or systemic blood pressure, and was not associated with serious adverse effects. At doses of 15 and 30 microg/kg, CVT-510 produced transient second/third degree AV heart block in all four patients treated. One of these patients also had a prolonged sedative effect that was reversed with aminophylline.


CONCLUSIONS
CVT-510 promptly prolongs AV nodal conduction and does not affect sinus rate or blood pressure. Selective stimulation of the A(1)-adenosine receptor by CVT-510 may be useful for immediate control of heart rate in atrial fibrillation/flutter and to convert paroxysmal supraventricular tachycardia to sinus rhythm, while avoiding vasodilatation mediated by the A(2)-adenosine receptor, as well as the vasodepressor and negative inotropic effects associated with beta-adrenergic receptor blockade and/or calcium channel blockers.
Lerman
B B
BB
Department of Medicine, Division of Cardiology, New York Hospital-Cornell University Medical Center, 525 East 68th Street, New York, NY 10021, USA.
Ellenbogen
K A
KA
Kadish
A
A
Platia
E
E
Stein
K M
KM
Markowitz
S M
SM
Mittal
S
S
Slotwiner
D J
DJ
Scheiner
M
M
Iwai
S
S
Belardinelli
L
L
Jerling
M
M
Shreeniwas
R
R
Wolff
A A
AA
D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001283:Atrioventricular Node / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005663:Furans / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D058906:Purinergic P1 Receptor Agonists; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000502:physiology
D005663:Furans; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; C118601:tecadenoson; D000241:Adenosine