In addition to clinical trials, investigators at NYU Langone Medical Center's Cardiac Electrophysiology/Heart Rhythm Center also conduct laboratory research to decipher the cellular mechanisms that initiate and sustain cardiac arrhythmias, especially atrial fibrillation (AF). Led by Dr. Douglas Holmes, the scientists use a rabbit model of myocardial infarction to study the cellular changes induced by pressure overload atrial dilation. They accomplish their work by scrutinizing myocytes with a new confocal microscope generously donated by Leon Charney.

The most common variety of atrial fibrillation develops in patients with abnormally large atrial dimensions associated with hypertensive, atherosclerotic, and valvular heart disease. These atria have electrophysiological changes that promote fibrillation, such as conduction velocity slowing and refractory period lengthening. While atria are hypokinetic after AF, it is not known to what extent these dilated cardiac structures are hypokinetic prior to AF. Histological evidence, however, does suggest dysfunction. The electrical changes could be the consequence of compensatory mechanisms in the face of atrial contractile failure. NYU investigators propose that atrial fibrillation is most closely related to atrial contractile failure, that this failure is slowly progressive until a threshold level is reached beyond which AF is inevitable, and that this contractile failure will be manifest both clinically and at the cellular level.

At the cellular level, the researchers are investigating the electrophysiologic alterations underlying abnormal automaticity and triggered activity. Failing cardiac tissues undergo remodeling of their ion handling proteins, characterized by up or down regulation of protein expression. In general, these changes tend to amplify subthreshold electrical events into triggered activity. While the mechanisms behind ventricular ectopy have become well characterized, those of the atrium are less well understood.

Among the differences between atrial and ventricular cells is the presence of IP3 receptors in atrial tissue. These calcium-releasing receptors are up-regulated in failing atrium, and may play a role in both triggered activity within the atrial free wall and abnormal automaticity from spontaneously firing cells within the pulmonary veins. Using confocal microscopy and patch clamp techniques, in a collaboration with the laboratory of Drs. William Coetzee and Michael Artman, the investigators simultaneously measure subcellular calcium transients and sarcolemmal membrane currents. Interactions between excitation-contraction mechanisms and IP3 calcium release could form the basis of new atrial specific therapeutic targeting.

Cardiac Electrophysiology/Heart Rhythm Center

403 East 34th Street, RIV-2nd Floor
New York, NY 10016
Phone: 212-263-7149

Larry A. Chinitz, M.D.
Director, The Heart Rhythm Center

Neil E. Bernstein, M.D.
Assistant Director, The Heart Rhythm Center

Douglas S. Holmes, M.D.
Assistant Professor of Medicine

Anthony Aizer, M.D.
Instructor of Medicine