Intracardiac electrophysiology to characterize susceptibility to ventricular arrhythmias in murine models

Area of Science:

• Cardiology
• Genetics
• Physiology

Background:

• Sudden cardiac death (SCD) and ventricular fibrillation are critical complications of cardiovascular diseases.
• Genetic conditions like channelopathies and cardiomyopathies are leading causes of SCD in young individuals.
• Effective experimental models are crucial for studying arrhythmia mechanisms and developing therapies.

Purpose of the Study:

• To adapt and validate a programmed electrical stimulation (PES) protocol for arrhythmia induction and recording in mice.
• To compare arrhythmia susceptibility between transgenic mouse models and control groups.
• To provide a detailed protocol for PES in mice, including catheterization, stimulation, and ECG interpretation.

Main Methods:

• Programmed electrical stimulation (PES) adapted from clinical practice was applied to two transgenic mouse models (Brugada syndrome, cardiolaminopathy) and controls.
• Intracardiac catheterization via the jugular vein was used for right ventricular stimulation and electrophysiological recording.
• Progressive stimulation protocols with a limited number of right ventricular extrastimuli were employed.

Main Results:

• The PES protocol successfully differentiated arrhythmia phenotypes between control and diseased mice.
• Transgenic mouse lines exhibited a higher susceptibility to triggered ventricular arrhythmias compared to controls.
• Detailed procedural information and ECG interpretation guidelines for PES in mice were provided.

Conclusions:

• This adapted PES technique is a valuable tool for characterizing arrhythmias in murine models.
• The study successfully phenotyped two arrhythmogenic-disease mouse models, revealing distinct rhythmic phenotypes.
• This method facilitates the study of arrhythmogenicity and the testing of novel antiarrhythmic treatments in genetically modified mice.