MODELS OF ECTOPIC ATRIAL AUTOMATICITY

Atrioventricular valve leaflets and atrial trabeculae from rabbit
hearts will be used in experimental models of ectopic atrial
automaticity designed to examine the electrophysiologic
determinants of exit block. First, spontaneously active valve
leaflets maintained in vitro will be mapped with microelectrodes
to identify sites of local conduction delay and block and to
characterize the electrophysiologic organization of ectopic foci.
The role of anisotrophy in exit block will be examined by
correlating experimentally measured indices of impaired
conduction with histologic analyses of cell orientation. Second,
the sucrose gap technique will be used in experiments aimed at
studying the source-sink relationship between leading pacemaker
fibers and their contiguous neighbors. This model will be applied
to the study of mechanisms by which autonomic neurotransmitters
conceal or unmask existing ectopic activity and alter manifest
pacemaker periodicity. Also the relative efficacy and site of
action of antiarrhythmic drugs will be analyzed on the basis of
induced changes in the source-sink relationship. Finally, sucrose
gap experiments will be extended to include a model of abnormal
automaticity using isolated atrial trabeculae partly exposed to
Ba2+. Source-sink factors in this model and antiarrhythmic drug
actions will be examined and compared with properties of normal
automaticity observed in valve tissue. The clinical revelance of these studies relates to a more precise
understanding of those factors that are most important for the
expression of ectopic automaticity in the intact human heart.
This information may be of use in identifying effective
pharmacologic approaches for the management of intermittent or
sustained atrial tachyarrhythmias.