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Sterile Pericarditis in Aachener Minipigs As a Model for Atrial Myopathy and Atrial Fibrillation
Published on: September 24, 2021
Effect of n6-cyclopentyladenosine on ouabain-induced toxicity in isolated Guinea pig atria
A Bakhtiarian1, M-J Hosseini, A Pousti
1Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Abstract:
ABSTRACT The effect of N6-cyclopentyladenosine (CPA), an A(1)-selective adenosine agonist, was studied on ouabain-induced toxicity in spontaneously beating isolated guinea pig atria. CPA (2-16 nM) produced a dose-dependent decrease in the force of contractions (34%-51%) and in the rate of contractions (22%-48%). CPA significantly increased the time of onset of arrhythmia (toxicity) induced by ouabain (1.2 muM) when it was administered 10 min before ouabain was added in organ bath. Ouabain (1.2 muM) alone produced arrhythmia at 7 min and either asystole or standstill at 22 min. CPA (8 nM) increased the time required to produce arrhythmia to 27.5 min and prolonged beating atria to more than 63 min and prevented the occurrence of asystole. These findings indicated that CPA produces direct cardiac action, probably due the inhibition of cardiac Na(+) and Ca(2+) channels. Moreover, our results suggest that CPA may reduce the membrane conduction through inhibition of ionic channels, which decrease ouabain-induced toxicity.
Insights
N6-cyclopentyladenosine (CPA), an A(1)-selective adenosine agonist, reduces cardiac contractility but protects guinea pig atria against ouabain-induced toxicity by delaying arrhythmia onset and preventing asystole.
Area of Science:
- Cardiology
- Pharmacology
- Cardiac Electrophysiology
Background:
- Ouabain is a cardiac glycoside that induces toxicity by inhibiting the Na+/K+-ATPase pump.
- Adenosine receptor agonists can modulate cardiac function and potentially counteract cardiotoxicity.
Purpose of the Study:
- To investigate the effect of N6-cyclopentyladenosine (CPA), an A(1)-selective adenosine agonist, on ouabain-induced cardiotoxicity in isolated guinea pig atria.
Main Methods:
- Isolated spontaneously beating guinea pig atria were used to assess the effects of CPA on contractility and ouabain-induced toxicity.
- CPA was administered prior to ouabain exposure to evaluate its protective potential.
Main Results:
- CPA (2-16 nM) decreased atrial contraction force (34%-51%) and rate (22%-48%) in a dose-dependent manner.
- CPA significantly delayed the onset of ouabain-induced arrhythmia and prevented asystole, prolonging atrial beating.
- At 8 nM, CPA increased arrhythmia onset time to 27.5 min and maintained atrial function for over 63 min.
Conclusions:
- CPA exhibits direct cardiac actions, likely through inhibition of cardiac Na+ and Ca2+ channels.
- CPA may reduce membrane conduction, thereby mitigating ouabain-induced cardiotoxicity.
