Circus movement reentry commonly has been invoke as a mechanism for ventricular arrhythmias, yet the modes of initiation and perpetuation of reentry remain the subject of considerable debate and conjecture. The purpose of these studies is to identify the determinants of reentry and Purkinje-muscle junctions (PMJ) and to establish the mechanisms by which subthreshold electrical stimuli,ionic channel blocking agents and autonomic neurotransmitters modulate Purkinje-muscle reentry. These studies will utilize branched Purkinje-muscle preparations mounted in a partitioned bath. One PMJ will be superfused with normal Tyrode solution and the other PMJ will be superfused with a hyperkalemic, hypoxic and acidotic Tyrode solution. Multiple microelectrode recordings will be obtained simultaneously from both PMJs. The projected components of the reentry circuit are: a premature or postmature initiating stimulus; unidirectional anterograde conduction block at the PMJ superfused with altered Tyrode solution; circulation of the impulse around the functional obstacle crated by lack of electrical coupling between Purkinje and muscle cells except at the PMJ and ; marked retrograde activation delay and reentry at the previously blocked PMJ. The proposed mechanisms for these events are that reflection across the PMJ generates a premature stimulus that subsequently initiates reentry, where as time-dependent reduction of action potential amplitude, mediated by recovery of the early outward current, causes PMJ conduction block and the subsequent development of reentry following a postmature stimulus. Conduction block at the PMJ during attempted anterograde conduction is caused by the large electrical load, or sink to the large source generated by muscle. Drugs and neurotransmitters that alter the relationship between source and sink may facilitate or suppress reentry accordingly. Further experiments will test the hypothesis that sustained Purkinje-muscle reentry represents a biological oscillator whose period can be advanced, delayed, entrained or annihilated by properly timed subthreshold stimuli delivered to the PMJ. Phase plane trajectories of the reentry circuit will be analyzed to gain insights concerning the nonlinear behavior of reentry. These studies promise to define the mechanisms by which reentry is initiated and sustained and to suggest new ways whereby reentry can be modified.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL040800-02
Application #
3358037
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1989-04-01
Project End
1994-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Gilmour Jr, R F; Otani, N F; Watanabe, M A (1997) Memory and complex dynamics in cardiac Purkinje fibers. Am J Physiol 272:H1826-32
Otani, N F; Gilmour Jr, R F (1997) Memory models for the electrical properties of local cardiac systems. J Theor Biol 187:409-36
Watanabe, M; Gilmour Jr, R F (1996) Strategy for control of complex low-dimensional dynamics in cardiac tissue. J Math Biol 35:73-87
Pacioretty, L M; Gilmour Jr, R F (1995) Developmental changes of action potential configuration and I(to) in canine epicardium. Am J Physiol 268:H2513-21
Watanabe, M; Otani, N F; Gilmour Jr, R F (1995) Biphasic restitution of action potential duration and complex dynamics in ventricular myocardium. Circ Res 76:915-21
Gilmour Jr, R F; Watanabe, M (1994) Dynamics of circus movement re-entry across canine Purkinje fibre-muscle junctions. J Physiol 476:473-85
Cai, Q; Tapper, D N; Gilmour Jr, R F et al. (1994) Modulation of the excitability of avian peripheral nerves by vitamin D: relation to calbindin-D28k, calcium status and lipid composition. Cell Calcium 15:401-10
Pacioretty, L M; Cooper, B J; Gilmour Jr, R F (1994) Reduction of the transient outward potassium current in canine X-linked muscular dystrophy. Circulation 90:1350-6