Depressant effect of adenosine in isolated human and canine atrial fibres.
STUDY OBJECTIVE0--he aim was to explore the cellular mechanisms responsible for the depressant effects of adenosine in human atrial tissues.


METHODS
Conventional microelectrode technique was used to record transmembrane action potential of human atrial tissues obtained at cardiac surgery. Effects of adenosine (0.1-100 microM) on action potential characteristics and contractile force of human atrial fibres in the absence and presence of an adenosine receptor antagonist (DPSPX) were evaluated. Results were then compared with those obtained from the canine atrial tissues.


METHODS
Atrial tissues obtained from hearts of 25 patients undergoing corrective cardiac surgery were used. Seven mongrel dogs were anaesthetised and strands of atrial muscle were removed and used for comparison.


RESULTS
In human atrial fibres showing fast response action potential (mean dV/dtmax around 100 V.s-1) in normal [K]o (4 mM) Tyrode solution, adenosine (1 nM-10 microM) did not induce consistent effects on the action potential characteristics. When the fibres were depolarised in high [K]o (27 mM) or in atrial fibres showing slow response action potential (dV/dtmax less than 50 V.s-1), however, 10 microM adenosine reduced the upstroke velocity and the amplitude of action potential significantly and markedly depressed the contractile force. In atrial fibres spontaneously active in normal Tyrode solution (maximum diastolic potential around -50 mV), adenosine inhibited rate of spontaneous discharge in a concentration dependent manner. Delayed afterdepolarisation and aftercontraction induced by adrenaline or/and high [Ca]o were also suppressed. The depressant effects of adenosine were blocked after pretreatment with 50 microM DPSPX, a specific antagonist for adenosine receptor.


CONCLUSIONS
These findings show that adenosine may abolish abnormal automatic rhythms and triggered activity in human atria.
Wang
G Y
GY
National Defence Medical Centre, Taipei, Taiwan, Republic of China.
Wei
J
J
Lin
C I
CI
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003470:Culture Media; D046508:Culture Techniques; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology
D003470:Culture Media; D001285:Atropine; D013806:Theophylline; D000241:Adenosine; D000109:Acetylcholine