Effects of ajmaline on rate-dependent atrioventricular node properties. Potential role in experimental atrioventricular re-entrant tachycardia.
Ajmaline is a well-known atrioventricular (AV) node depressant agent, but its effects on functional properties of the AV node and on experimental AV re-entrant tachycardia have not been explored. The aims of the present study were (1) to determine whether ajmaline administration modifies the rate-dependent properties of the AV node and (2) to correlate these changes with the actions of ajmaline on an in vitro model of AV re-entrant tachycardia. Selective stimulation protocols and mathematical formulations were used to quantify independently AV node recovery, facilitation, and fatigue in 10 isolated rabbit AV nodes. Ajmaline decreased facilitation and fatigue and had no significant effect on AV node recovery. The most important effect of ajmaline was rate-induced prolongation of AV node effective refractory period, resulting in a greater increase in tachycardia cycle length. AV re-entrant tachycardia was sustained when AV effective refractory period divided to tachycardia cycle length was less than 1, ajmaline suppressed AV re-entrant tachycardia by increasing the slope of the AV effective refractory period divided to tachycardia cycle length versus tachycardia rate relation, causing the critical ratio of 1 to be attained at a slower rate. A mathematical model incorporating quantitative descriptors of recovery, facilitation, and fatigue accounted for changes in nodal conduction time, AV effective refractory period, tachycardia cycle length, and AV effective refractory period divided to tachycardia cycle length under all conditions. It can be concluded that (1) ajmaline increases AV conduction time, decreases AV node fatigue, and facilitation, without altering AV node recovery. (2) Ajmaline significantly prolongs AV effective refractory period in a rate-dependent manner. (3) These changes play a role in ajmaline's actions on experimental AV re-entrant tachycardia. Ajmaline's ability to terminate re-entrant supraventricular tachycardia may be due, at least in part, to its ability to amplify the rate-induced prolongation of the nodal refractory period.
Nayebpour
M
M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 19835-355, Tehran, Iran. m_Nayeb_2000@yahoo.com
Naseri
M
M
Khori
V
V
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000404:Ajmaline / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001283:Atrioventricular Node / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008955:Models, Cardiovascular; D011817:Rabbits; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D000404:Ajmaline