Biological pacemakers: The oscillatory road ahead

Abstract

f ( a p a v p n c i s i o w l i v n n The rhythmic contraction of the mammalian heart depends on the coordinated periodic electrical discharges of thousands of electrically coupled pacemaker cells comprising the sinoatrial node. Periodic excitation by and propagation from the sinoatrial node is of paramount importance for normal cardiac function and can occur up to 3 billion times in the lifetime of an individual. A disruption in such a atural pacemaking ability has serious consequences, inluding bradycardia, syncope, arrhythmias, and death. The advent of electronic pacemakers has arrested the progressive detrimental effects of a dysfunctional sinus rhythm. However, electronic pacemakers come with their own set of problems: these include complicated technical maintenance, device or lead malfunction, associated infections, and the difficulty in treating pediatric patients, whose heart is still in the developmental stage. As a result, researchers in the last 15 years or so have begun addressing the challenge of creating alternative therapies, in the form of so-called biological pacemakers. The long-term goal of this research endeavor is to create robust pacemakers by using “natural elements” that are far superior than the currently available electronic pacemakers and last a lifetime, via manipulating endogenous genes, by exogenous cell therapy, or a combination thereof. Although many researchers ave made important contributions, 2 groups have been at he forefront in this area, one led by Dr Eduardo Marban, ormerly at Johns Hopkins University, now at Cedarsinai Heart Institute in Los Angeles, and Dr Michael R. osen, at Columbia University and SUNY Stonybrook. he goals of these 2 groups are similar: to understand the echanisms governing cardiac impulse initiation, with he idea of constructing a clinically applicable biological acemaker. But their approaches are different, the forer using techniques derived from gene therapy and the atter using cell therapy methodology.