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Introduction Fatal arrhythmias such as ventricular fibrillation (VF) are a major cause of sudden cardiac death (SCD), accounting for >100,000 deaths per year in the UK. Autonomic dysfunction is a hallmark of cardiac diseases like chronic heart failure post-myocardial infarction (MI) and is associated with increased arrhythmia risk although the underlying mechanisms remain unclear. Acute MI treatment aims to restore blood flow but there is an elevated risk of fatal arrhythmia development, particularly VF following MI. How occlusion duration affects electrophysiological and structural remodelling, autonomic modulation and arrhythmia susceptibility remains poorly understood. The aim of this study was to investigate how varying periods of coronary occlusion can impact cardiac electrophysiology and arrhythmia susceptibilityMethods New Zealand White Male Rabbits (2.2-2.5kg) underwent coronary artery ligation surgery with temporary occlusion for either 80 (MITO_80_8) or 40 minutes (MITO_40_8). After 8-weeks, histology or ventricular electrophysiology experiments were conducted. Histology (n=5/group) assessed scar size and structural remodelling using Evans blue and Triphenyl tetrazolium chloride. Ventricular electrophysiology (n=3/group) assessed effective refractory period (ERP), action potential duration (APD), APD restitution (APDR) and VF threshold at baseline and during vagal and sympathetic stimulation using four monophasic action potential (MAP) electrodes in different left ventricle regions.Results Histology showed more heterogenous, and patchy infarct in MITO_40_8 compared to MITO_80_8. Temporary occlusion increased the border region at the apex compared with permanent occlusion (MITO_40_8 11%, MITO_80_8 3.4% and permanent 1.5%) and in the mid-region of the heart (MITO_40_8 6.7%, MITO_80_8 1%) as seen in figure 1. Despite these structural differences, APDRmax and ERP were comparable between both groups across MAP locations and autonomic conditions, with preserved spatial gradients. In contrast, VFT was consistently lower in MITO_40_8 compared with MITO_80_8 under all conditions as shown in figure 2. With baseline VFT (2.4±0.5 vs 4±1.8), during vagal stimulation (4±0.8 vs 5±1.9), and during sympathetic stimulation (1.5±0.5 vs 2±0.2) indicating heightened VF vulnerability despite comparable repolarisation metrics. Although, autonomic influence on global repolarisation were limited, autonomic stimulation unmasks differences in VF vulnerability.Conclusion Shorter occlusion periods are associated with increased infarct heterogeneity and expansion of the border region as well as greater vulnerability to VF despite preserved global repolarisation and refractoriness. These findings highlight the importance of occlusion duration in shaping post-MI arrhythmic risk and support the translational relevance of this model.Abstract 278 Figure 1A) The average border region percentage across the heart in respect of region (apex, mid and base) for the five surgery groups as calculated through ImageJ. The three surgery groups with an n of 5 per group were permanent occlusion at 8 weeks remodelling (MIPO_8), 80-minute temporary occlusion following 8 weeks remodelling (MITO_80_8) and 40-minute temporary occlusion following 8 weeks remodelling (MITO_40_8). Individual values are plotted for each surgery group with bars representing mean ± SEM. Significant differences were identified through a two-way ANOVA with significant p values labelled * = ≤0.05 and ** = ≤0.01. B) Histology slice (Apex 2) from an 80-minute temporary occlusion following 8-week recovery. Different tissue regions are signified by different dotted lines as conducted in analysis. Healthy tissue is in blue and encircled by a blue dotted line, Border region is seen in red and infarct region is in white. The orientation of the histology slice is shown by the notation of the left and right ventricleAbstract 278 Figure 2The ventricular fibrillation threshold (VFT) without (baseline) and with autonomic stimulation (vagus or sympathetic). The VFT average border region percentage across the heart in respect of region (apex, mid and base) for the two surgery groups. The two surgery groups with 80-minute temporary occlusion following 8 weeks remodelling (MITO_80_8, n=3) and 40-minute temporary occlusion following 8 weeks remodelling (MITO_40_8, n=4). Individual values are plotted for each surgery group with bars representing mean ± SEM. No significant differences were identified through a two-way ANOVA