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Project

BLOOD PRESSURE INDUCED PREMATURE VENTRICULAR BEATS AS TRIGGERS FOR VENTRICULAR ARRHYTHMIA IN ISCHEMIC CARDIOMYOPATHY

Sudden cardiac death (SCD) by ventricular arrhythmia (VA) is an important cause of death in patients with coronary artery disease. The occurrence of SCD varies in time similar to variations of blood pressure suggesting a pro-arrhythmic effect of fluctuations in sympathetic tone and afterload. We demonstrated previously in healthy pigs that an acute blood pressure increase resulted in an abrupt left ventricular pressure decline, which had a profound effect on myocardial mechanics with enhanced post-systolic shortening and coincided with induced transient depolarizations and pressure-induced premature beats (PVBs). We moreover have a vast experience with a pig model of ischemic cardiomyopathy (ICMP) at risk for VA.In this project we want to elucidate the cellular mechanisms of the origin of PVBs and to provide evidence that these PVBss arising from the myocardial infarct border zone can trigger VA in ICMP. We hypothesize that regional changes in adrenergic innervation and mechano-sensitivity of Ca2+ signaling are responsible for this mechano-electrical coupling and that the border zone of an infarct is a specific “area at risk” for the genesis of PVBs because of the increased strain on this region, increased oxidative stress and regional changes in cardiac innervation. With specific pharmacological tools, merging of cardiac activation maps with information derived from simultaneous PET and MRI imaging we will clarify the pathophysiologic and regional origin of these PIPBs as triggers for VA.
Date:1 Oct 2018 →  Today
Keywords:sudden cardiac death, cardiomyopathy, coronary artery disease, ventricular arrhythmia, infarct border zone, mechano-electrical feedback
Disciplines:Cardiac and vascular medicine