Clinical trial NCT05034419: Synaptic Plasticity in the Epicardial Ganglionated Plexi
Official title: Synaptic Plasticity in the Epicardial Ganglionated Plexi
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Atrial Fibrillation
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
First posted: 2021-09-05
Enrollment: 90
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Atrial fibrillation (AF) is the most common arrhythmia and the prevalence increase with age. Autonomic nervous system play a critical role in the initiation and maintenance of AF. The intrinsic cardiac autonomic nervous system includes ganglionated plexus (GP) modulate the level of parasympathetic activity to the heart. Experimental and clinical studies suggest that GP activation plays a significant role in clinical AF in both the initiation of and the maintenance of AF.

Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the GP neurons innervating the heart. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by GP neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation.

Low level tragus stimulation (LLTS) has been shown to decrease AF burden among patients with paroxysmal AF. However, the exact mechanism remains unclear. The objective of this study is to examine changes in synaptic density of GP neurons in patients with paroxysmal AF and persistent AF compared to those without AF undergoing cardiac surgery. In addition, we aim to examine the effect of LLTS on the synaptic plasticity of the GP neurons. A group of patients undergoing open heart surgery will be randomized to active LLTS for 30 min (pulse width of 200 μs, amplitude of 20 mA and a pulse frequency of 20 Hz) or no stimulation. Biopsy from GP tissue will be taken immediately after stimulation and histological staining for choline acetyl transferase (ChAT), tyrosine hydroxylase (TH) and synaptophysin will be performed to examine synaptic plasticity.

Understanding the effect of LLTS on GP SP will help to determine whether changes in synaptic plasticity can increase or decrease autonomic tone of the heart, and its role in generating the aberrant electrical impulses in the GP around the pulmonary veins that can trigger and drive AF.


Eligibility criteria: Inclusion Criteria:

1. Male and female patients older than 21 year old
2. Patient is going to have open heart surgery.

Exclusion Criteria:

1. Patients undergoing emergent open heart surgery.

Primary outcomes:
measure: choline acetyltransferase
timeFrame: 30 minutes
measure: tyrosine hydroxylase
timeFrame: 30 minutes
measure: synaptophysin
timeFrame: 30 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: OU Medical Center
state: Oklahoma
Study officials:
References: