Introduction: Ventricular fibrillation (VF) is a malignant arrhythmia associated with Sudden cardiac death (SCD). There is no effective therapies to prevent SCD highlighting the importance of better understanding of VF mechanisms. The electrical restitution property of the heart has been used to determine arrhythmia susceptibility. This is the relationship between Action potential duration (APD) and diastolic interval (DI). Sequential APD changes during VF are believed to still be impacted by preceding APD and DI, referred to as cardiac memory, which could play an important role in VF initiation.   Electrical heterogeneity also influences cardiac restitution and arrhythmia susceptibility which can be impacted by pacing location.   This study investigates the relationship between APD and DI during VF and the impact of pacing location on restitution, in order to better understand the mechanisms underlying VF initiation.  

Methods: New Zealand White Male Rabbits (3-3.5kg) n=8 were sedated via subcutaneous injection (0.2mg/kg Sedator, 10mg/kg Ketamine and 0.01mg/kg Torbugesic). Hearts were isolated for a Langendorff heart preparation. Monophasic Action Potentials (MAPs) were recorded from the apex and base of the left ventricle epicardium. Pacing stimulation protocols such as effective refractory period (ERP), Action potential duration (APD), S1 delay, S2 delay, and standard restitution were conducted from five pacing sites. There were four epicardial pacing sites – Right Ventricle (RV) apex epicardium (epi), RV base epi, left ventricle (LV) apex epi and LV base epi and one endocardial site RV apex. Epicardial Pacing location was randomised. A VF pacing protocol was conducted via pacing at the endocardial site. 

Results: There were no significant differences in APD restitution (APDR) max, conduction velocity restitution (CVR) or ERP with pacing at the different locations. However, significant differences were identified in S1and S2 delay when comparing pacing locations. There was a significant difference between LV Apex Epi and RV Base epi for S1 and S2 delay (p≤0.005) from the Apex MAP recordings. Significant differences were also identified from the Base MAP recordings between LV Base epi and RV Apex epi (p≤0.01). During VF, a negative relationship was found between APD and preceding DI (up to n-5), but this relationship disappeared after 30 beats (Apex R value = -0.45) with no distinct relationship being found after 90 beats (Apex R value = -0.05). A positive relationship was found between APD and preceding APD (up to x-5) but the similar lack of relationship was found with an average decrease in R value of 0.3. 

Conclusions: This study showed that there are no significant differences on electrical restitution when comparing pacing sites except for S1 and S2 delay where there is a distance effect. It was found that there is a relationship within the first 30 beats of VF between APD and DI.  These findings highlight the potential of restitution analysis to capture VF dynamics within the first 30 beats of onset. The observation that VF may exhibit non-random, memory-dependent patterns suggests that exploiting this could enable more precise timing of defibrillation and ultimately improve clinical outcomes.