This work will use a novel laser scanning system to investigate the causes of certain cardiac arrhythmias. Both atrial flutter and ventricular tachycardias are serious health problems in the United States. Reentry is strongly implicated in causing these arrhythmias, and the proposed research addresses several crucial issues regarding the mechanisms that allow reentry to develop and to be terminated: - the spatial interplay of slowed conduction and recovery of excitability in predisposing cardiac tissue to reentry, - effects of myocardial fiber orientation in establishing the above conditions, and - the mechanisms by which therapeutic interventions can effectively interrupt this arrhythmogenic process. The investigations will utilize a laser scanner that monitors electrical activity from myocardium stained with a fluorescent, voltage-sensitive dye. Both endocardium and epicardium can be monitored simultaneously at 64 points on each surface. High-resolution activation maps will be obtained under conditions of tachycardia induced by premature stimulation. The studies will determine whether stimulation during the relative refractory period induces reentry by causing a shift from fast conduction along the direction of myocardial fibers to a condition of slow conduction perpendicular to fiber orientation. This issue will be examined in guinea pig and rabbit myocardium, and the effects of antiarrhythmic drugs and programmed stimulation on underlying mechanisms will be determined. Results, in the form of electrical propagation maps, will allow us to directly observe the spatial and temporal relationships involved in the initiation and termination of reentrant circuits, and to correlate these results with histological evidence regarding fiber orientations.
