Related Experiment Video

Updated: Feb 3, 2026

Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats
05:12

Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats

Published on: February 14, 2022

3.8K

Atrial Fibrillation Initiated by Early Afterdepolarization-Mediated Triggered Activity during Acute Oxidative Stress:

Arash Pezhouman1, Hong Cao2, Michael C Fishbein3

  • 1Translational Arrhythmia Section, UCLA Cardiovascular Research Laboratory, USA.

Journal of Heart Health
|November 6, 2018
PubMed
Abstract

Insights

Oxidative stress activates Ca-calmodulin dependent protein kinase (CaMKII), initiating atrial fibrillation (AF) through early afterdepolarizations in aged, fibrotic atria. Blocking the late sodium current (INa-L) with GS-967 effectively suppressed this oxidative AF.

Area of Science:

  • Cardiology
  • Electrophysiology
  • Oxidative Stress Research

Background:

  • The mechanisms underlying atrial fibrillation (AF) triggered by acute oxidative stress are not well understood, and current drug therapies are often suboptimal.
  • Aged atrial tissue exhibits increased fibrosis, potentially predisposing it to arrhythmias.

Purpose of the Study:

  • To investigate the role of Ca-calmodulin dependent protein kinase (CaMKII) activation in oxidative stress-induced AF.
  • To determine if blocking the late sodium current (INa-L) can suppress AF originating from early afterdepolarizations (EADs).

Main Methods:

  • Utilized high-resolution voltage optical mapping and microelectrode recordings in isolated-perfused rat hearts.
  • Induced AF using hydrogen peroxide (H2O2) in aged and young atria.
  • Administered CaMKII inhibitor (KN-93) and INa-L blocker (GS-967) to assess their effects on AF.

Main Results:

  • Aged atria (23-24 months) showed a 10-fold increase in fibrosis and spontaneously developed AF (39/41 hearts) during H2O2 perfusion, unlike young atria (0/12 hearts).
  • AF initiation was linked to focal EAD-mediated triggered activity in the left atrium.
  • Both KN-93 and GS-967 significantly suppressed H2O2-induced AF.

Conclusions:

  • Oxidative activation of CaMKII, in the context of atrial fibrosis, initiates AF via EADs.
  • Specific blockade of INa-L with GS-967 is a promising therapeutic strategy for suppressing oxidative AF.
  • Targeting INa-L offers a potential new approach for treating human AF where conventional therapies are insufficient.
Keywords:
Atrial fibrillationCAMKIIEarly afterdepolarizationsFibrosisGS-967Hydrogen PeroxideLate inward sodium currentOptical activation map

More Related Videos

Robotic Ablation of Atrial Fibrillation11:21

Robotic Ablation of Atrial Fibrillation

Published on: May 29, 2015

20.2K
Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation28:13

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Published on: February 26, 2013

34.1K

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
11.9K
Amyloid Fibrils03:03

Amyloid Fibrils

6.4K
Neuromuscular Junction And Blockade01:29

Neuromuscular Junction And Blockade

The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
5.0K
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
39.0K
Initiation of Translation02:33

Initiation of Translation

8.1K
Oxidation Numbers03:14

Oxidation Numbers

In redox reactions, the transfer of electrons occurs between reacting species. Electron transfer is described by a hypothetical number called the oxidation number (or oxidation state). It represents the effective charge of an atom or element, which is assigned using a set of rules.
42.6K