Abstract 14844: An in vitro Model of Early- and No-Reperfusion-Scars to Understand Differences in Reentrant Arrhythmia Characteristics and Potential Therapeutic Interventions
Purpose: Early-reperfusion therapy for myocardial infarction (MI) causes patchy scars, whereas no reperfusion causes compact scars. Patchy scars show lower inducibility and shorter cycle length of ventricular tachycardia compared to compact scars. Despite the increasing number of reperfused patients there is little data on arrhythmia mechanisms. We investigated the applicability of an in vitro model of patchy and compact scar pattern to gain a mechanistic understanding of associated arrhythmic characteristics.
Methods: Neonatal Rat Ventricular Monolayers were locally ablated at day 3 by laser-cut stamps of one ø6mm circle to mimick late-reperfused,compact scars (compacts). A circular arrangement of sixteen ø1.2mm circles with an outer diameter of 6mm mimicked early-reperfused, patchy scars (patchies). At day 4, optical mapping was performed.
Results: Inducibility of reentry was lower in patchies (30%,n=23 vs 72%,n=11) and cycle length was shorter (252±33ms vs 325±43 ms,p<0.05) compared to compacts. Spiral-wave attachment to obstructions was 100% in compacts, but in 50% of patchies. Polymorphic arrhythmias were more prevalent in patchies, due to meandering and un/re-pinning, and excitability gradients were larger during arrhythmias. High-frequent electrical stimulation terminated arrhythmias less frequently in patchies (3 out of 6 vs 6 out of 6 in compacts) and could increase arrhythmic complexity due to wavebreaks. Nav1.5 blockade terminated 88% of arrhythmias in patchies but 25% in compacts.
Conclusions: An in vitro model of patchy and compact obstructions reproduces arrhythmic characteristics observed after early- and no- reperfused MI. Furthermore, it may provide mechanistic insights into potential efficacy of pharmacological and electrical termination of scar-related arrhythmias.
- © 2012 by American Heart Association, Inc.