EFFECTS OF ADENOSINE ON RATE-DEPENDENT ATRIOVENTRICULAR NODAL FUNCTION - POTENTIAL ROLES IN TACHYCARDIA TERMINATION AND PHYSIOLOGICAL REGULATION

Citation
M. Nayebpour et al., EFFECTS OF ADENOSINE ON RATE-DEPENDENT ATRIOVENTRICULAR NODAL FUNCTION - POTENTIAL ROLES IN TACHYCARDIA TERMINATION AND PHYSIOLOGICAL REGULATION, Circulation, 88(6), 1993, pp. 2632-2645
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiac & Cardiovascular System",Hematology
Journal title
ISSN journal
0009-7322
Volume
88
Issue
6
Year of publication
1993
Pages
2632 - 2645
Database
ISI
SICI code
0009-7322(1993)88:6<2632:EOAORA>2.0.ZU;2-N
Abstract
Background. Adenosine is well known to depress atrioventricular (AV) n odal conduction, but the potential interactions between adenosine and functional AV nodal properties have not been explored. The purpose of the present study was to determine (1) whether exogenous adenosine mod ifies the rate-dependent properties of the AV node, (2) to what extent such changes underlie the actions of adenosine in an in vitro model o f AV reentrant tachycardia (AVRT), and (3) the potential role of endog enous adenosine in rate induced AV nodal responses. Methods and Result s. The functional properties of AV nodal recovery (defining the conduc tion delay of a single premature activation), facilitation (effect of short cycles on subsequent nodal recovery), and fatigue (slowly develo ping AV nodal delay at a rapid rate) were studied selectively in isola ted, superfused rabbit and guinea pig cardiac preparations. Exogenous adenosine increased AV nodal fatigue and attenuated facilitation, resu lting in tachycardia-dependent increases in AH interval and AV nodal e ffective refractory period (AVERP). In experimental AVRT, adenosine ca used greater increases in tachycardia cycle length (T) and AVERP as ta chycardia rate increased. AVRT was sustained when AVERP/T was <1, and adenosine suppressed AVRT by increasing the slope of the AVERP/T versu s tachycardia rate relation, causing the critical ratio of 1 to be att ained at slower rates. A mathematical model incorporating quantitative descriptors of recovery, facilitation, and fatigue accounted for chan ges in AH interval, AVERP, tachycardia cycle length, and AVERP/T under control conditions and in the presence of adenosine. In the absence o f exogenous adenosine, I-phenyltheophylline (10 mu mol/L), an adenosin e receptor antagonist, did not alter recovery or facilitation but sign ificantly reduced rate-related fatigue (by 31+/-8%, mean+/-SEM, P<.05, in rabbit hearts; 46+/-5%, P<.01, in guinea pig hearts). Combined inh ibition of adenosine deaminase (with erythro-9-[2-hydroxy-3-nonyl]-ade nine hydrochloride, 5 mu mol/L) and adenosine uptake (with dipyridamol e, 1 mu mol/L) increased fatigue in the absence of exogenous adenosine by 57+/-20% (P<.05). Conclusions. We conclude that (1) exogenously ad ministered adenosine increases AV nodal fatigue and reduces facilitati on, without altering AV nodal recovery; (2) these changes cause rate-d ependent AV nodal depression, which plays a role in adenosine's action s on experimental AVRT; and (3) endogenous adenosine receptor activati on plays a role in physiological AV nodal fatigue. Adenosine's ability to terminate reentrant supraventricular tachycardia may be due, at le ast in part, to its ability to enhance the physiological conduction sl owing that results from sustained increases in AV nodal activation rat e.