Cell and gene therapy strategies for the treatment of postmyocardial infarction ventricular arrhythmias.
Ventricular arrhythmias in the setting of a healed myocardial infarction represent a major cause of morbidity and mortality. The underlying mechanism is the presence of slow conduction tissue within the infarct border zone. In the current review we describe experimental gene and cell therapy approaches targeting the electrophysiologic substrate of the border zone, with the aim of preventing postinfarction ventricular arrhythmias. These include strategies that aim to prevent reentry by improving conduction velocity or by prolonging refractoriness. Attempts to augment conduction velocity include cardiomyocyte transplantation to regenerate the infarct, overexpression of unique sodium channels (to improve excitability), and methods to improve cell-to-cell coupling. Strategies to prolong refractoriness include gene therapy to prolong action potential duration or cell therapy using engineered cell grafts transfected ex vivo to express unique potassium channels. Finally, we will also discuss the potential advantages and drawbacks of these strategies as well as a road map for future clinical use.
Gepstein
Lior
L
The Sohnis Family Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, The Bruce Rappaport Institute in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. mdlior@tx.technion.ac.il
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000601:surgery / Q000628:therapy*; D017690:Cell Transplantation; D015316:Genetic Therapy; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics* / Q000601:surgery / Q000628:therapy*