Colitis induced ventricular alternans increases the risk for ventricular arrhythmia.

Area of Science:

• Cardiology
• Gastroenterology
• Molecular Biology

Background:

• Inflammatory bowel disease (IBD) is associated with increased risk of cardiac conduction defects and ventricular arrhythmias.
• Gut dysbiosis, systemic inflammation, and renin-angiotensin system (RAS) deregulation are linked to IBD and may contribute to cardiac complications.

Purpose of the Study:

• To investigate the mechanisms by which colitis induces electrophysiological remodeling and increases the risk of ventricular arrhythmia.
• To explore the role of the renin-angiotensin system in colitis-associated cardiac electrical instability.

Main Methods:

• A mouse model of dextran sulfate sodium-induced colitis was used to assess cardiac electrophysiology during active inflammation.
• Electrocardiography, Langendorff-perfused heart electrophysiology (field potential recordings), and isolated ventricular myocyte studies (calcium transient analysis) were performed.
• The effects of SERCA activator (Istaroxime) and RAS inhibitors (ACE inhibitor, AT1R blocker) were evaluated.

Main Results:

• Colitis induced prolonged QT duration, increased field potential dispersion, and a higher propensity for ventricular alternans.
• Isolated myocytes showed increased calcium transient alternans and prolonged duration, linked to attenuated phospholamban phosphorylation.
• Inhibition of the renin-angiotensin system (ACE or AT1R blockade) prevented the increased alternans inducibility.

Conclusions:

• Active colitis promotes reversible remodeling of ventricular calcium handling, increasing the risk of arrhythmias like alternans.
• Renin-angiotensin system activation plays a key role in these colitis-induced cardiac electrophysiological changes.
• Targeting the RAS may offer a therapeutic benefit for managing cardiac risks in patients with active inflammatory bowel disease.