Objective:

To test whether selective activation of cholinergic neurons within the intrinsic cardiac ganglia (ICG) reduces arrhythmias and improves oxygenation of ischemic border zone tissue after an acute coronary occlusion, potentially offering a novel therapeutic strategy.

Key Findings:

• LAD ligation resulted in a significant drop in pO2 in the ischemic zone, highlighting the severity of ischemia.
• DREADDs-mediated cholinergic ICG activation prolonged the PR interval and reduced arrhythmia incidence, indicating a protective effect.
• Ischemic border zone pO2 increased significantly after cholinergic ICG activation, demonstrating improved oxygenation.
• NADH fluorescence trended lower in the ischemic zone, indicating increased mitochondrial oxidation, which is beneficial.
• Effects were blocked by the muscarinic antagonist atropine, confirming the mechanism of action.

Interpretation:

Selective stimulation of cholinergic ICG neurons could improve oxygen delivery to the ischemic border zone and reduce arrhythmias through a muscarinic-dependent mechanism, suggesting a new avenue for therapeutic intervention.

Limitations:

Conclusion:

The study supports further investigation of the intrinsic cardiac cholinergic network as a therapeutic target for early intervention in acute myocardial infarction, emphasizing the potential for improved patient outcomes.