Synaptic Plasticity in the Epicardial Ganglionated Plexi
- Conditions
- Atrial Fibrillation
- Interventions
- Device: Sham stimulationDevice: Parasym
- Registration Number
- NCT05034419
- Lead Sponsor
- University of Oklahoma
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- Male and female patients older than 21 year old
- Patient is going to have open heart surgery.
- Patients undergoing emergent open heart surgery.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sham stimulation Sham stimulation Patients undergoing cardiac surgery will be randomized to sham stimulation for 30 min. The Parasym device will be placed on the patient's tragus, but no current will be delivered. Active stimulation Parasym Patients undergoing cardiac surgery will be randomized to active low level tragus stimulation for 30 min (pulse width of 200 μs, amplitude of 20 mA and a pulse frequency of 20 Hz). Stimulation will be provided using the Parasym device.
- Primary Outcome Measures
Name Time Method synaptophysin 30 minutes Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for synaptophysin will be performed
choline acetyltransferase 30 minutes Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for choline acetyl transferase (ChAT) will be performed
tyrosine hydroxylase 30 minutes Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for tyrosine hydroxylase will be performed
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States