Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions.

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Arrhythmogenesis Research

Background:

• Ventricular tachycardia/fibrillation (VT/VF) rearrest post-resuscitation is a significant clinical challenge with poor survival rates.
• Impaired gap junctions (GJs) can exacerbate discordant alternans (DIS ALT), a proposed mechanism for VT/VF.
• Spontaneous in vivo demonstration of DIS ALT-induced VT/VF and the role of GJs remain unclear.

Purpose of the Study:

• To investigate the occurrence of spontaneous DIS ALT-induced VT/VF in vivo.
• To determine if preserving Cx43-mediated GJ coupling can suppress VT/VF rearrest.

Main Methods:

• Utilized a porcine model for in vivo resuscitation from cardiac arrest.
• Employed ex vivo optical mapping in porcine left ventricular wedge preparations.
• Administered rotigaptide and αCT11 to assess GJ effects on DIS ALT and VT/VF.

Main Results:

• In vivo DIS ALT frequently preceded VT/VF at normal and mild hypothermia temperatures.
• Rotigaptide significantly reduced DIS ALT and VT/VF incidence, particularly during mild hypothermia.
• Ex vivo, rotigaptide and αCT11 markedly reduced DIS ALT by improving action potential duration heterogeneity.

Conclusions:

• Provides strong in vivo evidence linking spontaneous DIS ALT to VT/VF in a clinically relevant setting.
• Suggests that preserving GJ coupling during resuscitation can effectively suppress VT/VF rearrest.
• Highlights the therapeutic potential of targeting GJs to prevent cardiac arrhythmias.