Acetylcholine release by a stimulus train lowers atrial fibrillation threshold

Area of Science:

• Cardiovascular Physiology
• Autonomic Nervous System
• Cardiac Electrophysiology

Background:

• The role of local autonomic neuromediators in cardiac electrical activity is not fully understood.
• Atrial fibrillation (AF) is a common arrhythmia influenced by autonomic tone.

Purpose of the Study:

• To investigate the impact of electrical stimulation on local autonomic neuromediator release in the right atrium.
• To determine the effect of these neuromediators on the atrial fibrillation threshold (AFT).

Main Methods:

• Experiments were conducted on anesthetized, denervated open-chest dogs.
• The AFT was measured using electrical stimuli (train or single pulse) applied to the right atrium.
• Pharmacological interventions included beta-adrenergic blockade (timolol) and muscarinic blockade (atropine).
• Monophasic action potentials were recorded to assess repolarization changes.

Main Results:

• Beta-adrenergic blockade did not affect the AFT.
• Atropine significantly increased the AFT when measured with a train of stimuli, but had a smaller effect with a single stimulus.
• Electrical stimulation trains caused marked shortening of atrial action potential duration, which was abolished by atropine.
• These findings suggest acetylcholine release contributes to reduced AFT.

Conclusions:

• Electrical stimulation of the atrium releases local acetylcholine.
• Acetylcholine release shortens atrial repolarization, significantly decreasing the current required to induce atrial fibrillation.
• Autonomic neuromediators play a critical role in modulating cardiac excitability and susceptibility to arrhythmias.