Age-dependent electrocardiographic changes in Pgc-1β deficient murine hearts

Area of Science:

• Cardiology
• Mitochondrial Biology
• Genetics

Background:

• Chronic energetic dysfunction is linked to human cardiac arrhythmias.
• Mitochondrial impairment, specifically Pgc-1β knockout, causes arrhythmias in mice.
• The combined effects of Pgc-1β knockout, aging, and electrocardiographic changes are not well understood.

Purpose of the Study:

• To investigate the impact of Pgc-1β knockout and aging on cardiac electrophysiology.
• To analyze electrocardiographic (ECG) changes in wild-type (WT) and Pgc-1β knockout mice of different ages.
• To determine the pro-arrhythmic substrate in Pgc-1β knockout mice.

Main Methods:

• Electrocardiographic (ECG) recordings were performed on young and aged WT and Pgc-1β knockout mice.
• Mice underwent a β1-adrenergic challenge using dobutamine.
• ECG intervals were analyzed for differences between groups before and after the challenge.

Main Results:

• Pgc-1β knockout mice showed impaired sino-atrial node function and atrioventricular conduction defects, especially when aged.
• Ventricular activation was prolonged in Pgc-1β knockout mice, indicating slowed conduction.
• Shortened repolarization intervals and a reduced QT interval were observed in Pgc-1β knockout mice, increasing arrhythmia risk.

Conclusions:

• Pgc-1β knockout exacerbates age-related cardiac dysfunction.
• Mice lacking Pgc-1β exhibit an electrocardiographic profile consistent with a pro-arrhythmic substrate.
• These findings highlight the role of mitochondrial function in cardiac electrical stability and aging.