The apicobasal dispersion of ventricular repolarization in humans is associated with age and affects arrhythmia vulnerability

作者：Vladimír Sobota, Job Stoks, Kiran Haresh Kumar Patel, Roshni Shetty, Haibo Ni, Eleonora Grandi, Fu Siong Ng, Paul G.A. Volders, Matthijs Cluitmans, Jason D. Bayer · 发表于：The Journal of Physiology · 年份：2025 · DOI：10.1113/jp288356 · 被引用次数：4 · 研究领域：Cardiac electrophysiology and arrhythmias、Cardiac Arrhythmias and Treatments、Cardiac pacing and defibrillation studies

The apicobasal repolarization gradient (ABRG) plays an important role in determining the sequence of ventricular repolarization, but the effects of sex and age on ABRG are unknown. In this study, we investigate the age- and sex-related differences in ABRG and evaluate their possible role in vulnerability to arrhythmia. Electrocardiographic imaging was performed in 22 healthy subjects (16 females and 6 males) during sinus rhythm, and the average recovery time (RT) at the ventricular apex and base was determined. Fifty-six different ABRGs were simulated in a male and female model of human ventricular epicardium with sex-specific electrophysiology by simultaneously adjusting the apicobasal gradients of the slow and rapid delayed rectifier potassium currents. The models were burst paced from the ventricular apex and right ventricular outflow tract to assess the effect of ABRGs on arrhythmia vulnerability. Apicobasal differences in RT (human subjects) and repolarization time (simulation data) were calculated to quantify the ABRGs. In human subjects, ABRGs diminished and eventually inverted (longer RT at the apex than at the base) with increasing age (r = -0.7265, P = 0.0001). In both male and female models, apical pacing resulted in arrhythmia in 20/ 56 simulations, whereas right ventricular outflow tract pacing resulted in arrhythmia in 15/56 simulations. Arrhythmias were attributable to re-entry from unidirectional block and generally lasted longer in the models with shorter RT ...