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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL038917-02
Application #
3471418
Study Section
Cardiovascular Study Section (CVA)
Project Start
1987-08-01
Project End
1992-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198