What is the physiological mechanism by which increased vagal tone prevents threshold capture in a leadless pacemaker?
GPT 4o answwer:
The inability of a leadless pacemaker to achieve threshold capture under conditions of increased vagal tone primarily results from neurocardiac modulation of myocardial excitability. The main physiological mechanisms involved are:
Mechanism: Vagal stimulation releases acetylcholine (ACh) at the sinoatrial (SA) node, atrioventricular (AV) node, and ventricular myocardium.
Effect on Myocytes:
ACh binds to muscarinic M2 receptors, activating inward rectifying IK,ACh channels.
This increases potassium efflux (K⁺), leading to hyperpolarization of the resting membrane potential.
Impact on Pacemaker Capture:
A hyperpolarized membrane requires a larger depolarizing stimulus to reach the threshold potential, often beyond what the pacemaker's programmed output can deliver.
Mechanism:
M2 receptor activation inhibits adenylyl cyclase, reducing cAMP levels.
Low cAMP decreases L-type calcium channel activity.
Impact:
Reduced calcium influx weakens myocardial excitability and slows depolarization.
Lower intracellular calcium also impairs contractility, compounding the difficulty of achieving effective capture.
Increased vagal tone slows conduction velocity and prolongs the effective refractory period by modulating ionic currents, making it more challenging for an external stimulus (pacemaker output) to depolarize the tissue during its excitable phase.
Vagal tone naturally increases during sleep, particularly in NREM Stage N3, and in certain body positions (e.g., right decubitus or prone), further promoting myocardial hyperpolarization and making capture thresholds more difficult to achieve at night.
Higher Output Settings: Sometimes necessary to overcome this barrier, though it drains battery faster and increases fibrosis risk.
Sensor-Driven Adjustments: Devices with active sensors (e.g., accelerometers or minute ventilation sensors) may help mitigate this effect by adjusting pacing during sleep or postural changes.
Alternative Leadless Technologies: Consideration of conduction system pacing (e.g., His bundle or left bundle branch pacing) where thresholds are generally lower and less affected by vagal tone.
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