Pathophysiological remodeling of cardiac function occurs at multiple levels, spanning the spectrum from molecular and sub-cellular changes to those occurring at the organ-system levels. Complex alterations in a host of ion channels, Ca2+-cycling proteins, and gap junction related molecules modulates key electrophysiological properties, predisposing to arrhythmias caused by enhanced automaticity, triggered activity, and reentry. Heart failure induced ion channel dysfunction prolongs the AP, increases spatiotemporal gradients of repolarization, promotes the formation of arrhythmogenic triggers and results in conduction abnormalities. Cell-based therapies can significantly improve left ventricular function. As such, these therapies may activate complex signaling processes that reverse remodel the failing heart, and therefore prevent the incidence of arrhythmias. On the other hand, cell based therapies might also alter the resting membrane potential, produce abnormal triggers, promote electrical heterogeneities, modulate conduction, and favor reentrant excitation. Of major concern is the fact that hESC-CMs and, by inference, iPSC-CMs, display a range of functional and structural properties that are remarkably similar to those of failing heart cells. These properties along with a detailed investigation of their electrophysiological consequences require careful investigation before their clinical efficacy can be further assessed.
|Original language||English (US)|
|Title of host publication||Ventricular Arrhythmia|
|Subtitle of host publication||From Principles to Patients|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||13|
|State||Published - Feb 1 2013|
ASJC Scopus subject areas