Electrophysiologic Effects of a Novel Selective Adenosine A1 Agonist (CVT-510) on Atrioventricular Nodal Conduction in Humans
| Autor: | Alan H. Kadish, Kenneth M. Stein, David J. Slotwiner, Bruce B. Lerman, Markus Jerling, Steven M. Markowitz, Revati Shreeniwas, Andrew A. Wolff, Luiz Belardinelli, Edward V. Platia, Suneet Mittal, Marc A. Scheiner, Sei Iwai, Kenneth A. Ellenbogen |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Agonist Tachycardia medicine.medical_specialty Adenosine medicine.drug_class Blood Pressure 030204 cardiovascular system & hematology Purkinje Fibers Electrocardiography 03 medical and health sciences Adenosine A1 receptor 0302 clinical medicine Bolus (medicine) Heart Rate Internal medicine Purinergic P1 Receptor Agonists medicine Humans Pharmacology (medical) Sinus rhythm 030212 general & internal medicine Furans Aged Pharmacology Dose-Response Relationship Drug business.industry Receptors Purinergic P1 Middle Aged Atrioventricular node Electrophysiology medicine.anatomical_structure Anesthesia Atrioventricular Node Cardiology Female medicine.symptom Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology and Therapeutics. 6:237-245 |
| ISSN: | 1940-4034 1074-2484 |
| DOI: | 10.1177/107424840100600304 |
| Popis: | Background: CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, is a selective A,-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-5 10 on AV nodal conduction and hemodynamics. Methods and Results: Patients in sinus rhythm with normal AV nodal function at electrophysiologic study (n = 32) received a single intravenous bolus of CVT-5 10. 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 pg/kg) caused a dosedependent increase in the AH interval. At 1 minute, a dose of 10,ug/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,ug/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 pg/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,-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 A2-adenosine receptor, as well as the vasodepressor and negative inotropic effects associated with 3-adrenergic receptor blockade and/or calcium channel blockers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|