alw4@columbia.edu

PROFESSOR OF PHARMACOLOGY

Mechanisms for arrhythmias caused by cardiac disease

Cardiac diseases cause the heart to beat abnormally, either with very rapid or very slow rhythms that often originate in areas modified by the disease. The abnormal rhythms, known as cardiac arrhythmias, compromise the ability of the heart to pump enough blood to meet the demands of the major organs of the body and may cause death. Our research is to determine why and how these abnormal rhythms occur, particularly in the setting of myocardial ischemia and infarction. We study the effects of ischemia caused by coronary artery occlusion on the initiation and propagation of electrical impulses in the intact heart of experimental animals. Computerized instrumentation has been designed to record the electrical activity at a large number of sites and to analyze the waveforms. This analysis enables us to determine why and how the arrhythmias are occurring. Once we learn the mechanisms, our long-term goal is to develop drugs that can restore the normal heart beat.

Selected Publications:

1. Peters NS, Coromilas J, Severs NJ, Wit AL:  Disturbed connexin 43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation 95:988-996, 1997. Abstract Full Text

2. Costeas C, Peters NS, Waldecker B, Wit AL. Coromilas J:  Mechanisms causing sustained ventricular tachycardias with multiple QRS Morphologies; results of mapping studies in the infarcted canine heart. Circulation 96:3721-3731, 1997. Abstract Full text

3. Peters NS, Coromilas J, Hanna MS, Josephson ME, Costeas C, Wit AL: Characteristics of the temporal and spatial excitable gap in anisotropic reentrant circuits causing sustained ventricular tachycardia. Circ. Res. 82:279-293, 1998.Abstract PDF file

4. Cabo C, Schmitt H, Wit AL: New mechanism of antiarrhythmic drug action: Increasing L-type calcium current prevents reentrant ventricular tachycardia in the infarcted canine heart. Circulation 102:2417-2425, 2000. Abstract PDF file

5. Chiello Tracy C, Cabo C, Coromilas J, Kurokawa J, Kass RS and Wit AL: Electrophysiological consequences of human I_Ks channel expression in adult murine heart. Am. J. Physiol. Heart Circ. Physiol. 284:H168-175, 2003. Abstract PDF File

Contour map showing the pattern of impulse propagation in an infarcted region of the canine heart is at the left. Each of the small numbers indicates the time at which the impulse reached the recording site. Isochrones are drawn at 10 msec intervals and are labelled with larger numbers. By following the sequence of numbers it can be seen that the electrical wavefront moves in a circular pattern. At the right are representative electrogram recordings.