A heterogeneous approach to understanding the mechanisms for reentry

This thesis presents the continuing research effort towards understanding the mechanisms in cardiac tissue that facilitate reentry, the process which is generally agreed upon to cause ventricular fibrillation. Fibrillation is an abnormal rhythm disorder where the heart does not contract in a coordinated manner to pump blood, but instead exhibits chaotic, dyssynchronous contraction characterized by the uncontrolled quivering or twitching of the muscle fibers; when it occurs in the lower chambers of the heart is it called ventricular fibrillation, which can rapidly progress to sudden cardiac death. Sudden cardiac death is the leading cause of death in the western, industrialized world, it is not fully understood and there is no known cure.;However, in recent years, the use of new technology called optical mapping has provided some interesting clues, one of which is the phenomena of cardiac muscle activation waves, responsible for contraction and which normally spread in a synchronous fashion across the surface of the heart, break into a dyssynchronous spread during ventricular fibrillation. This break in activation waves can cause the formation of spiral waves which re-activate tissue at a faster rate of uncoordinated contraction than would normally occur.;The first part of this thesis presents a useful tool for understanding cardiac wave dynamics by examining a well-known chemical oscillator: the Belousov-Zhabotinsky, or BZ, reaction. The BZ reaction serves as a chemical model of non-equilibrium thermodynamics present in biological processes such as in cardiac tissue. The chemical substrate of the BZ reaction is excitable, and can form activation waves just as those seen in the heart. These waves can also be perturbed to form spiral waves. This visual teaching exercise was presented to students of various backgrounds and degrees of education to understand cardiac wave dynamics and elicit interest in cardiac research, and it resulted in the paper Teaching cardiac electrophysiology modeling to undergraduate students: laboratory exercises and GPU programming for the study of arrhythmias and spiral wave dynamics. Adv Physiol Educ 35: 427.437, 2011;;One prominent theory on the mechanism of fibrillation is the process of reentry, which could be facilitated by heterogeneity within the muscle itself. The second part of this thesis presents the use of silicon microprobes with ultrasonic PZT actuators to reduce penetration force to measure action potential duration in canine left ventricular tissue. Platinum electrodes patterned on the microprobe transduce intramural membrane potentials to measure action potential duration and assess the degree of heterogeneity within the ventricle wall. This technique differs from other techniques that have been used to study intramural electrophysiology in that the mid-myocardial tissue remains in a syncytium that does not electrically decouple the tissue, such as with previous studies by sharp electrode impalement, optical mapping, or patch-clamp study which require sectioning the tissue with a dermatome, or dissociation into individual cells.;The third part of this thesis examines the role that the Purkinje fiber network itself may play in participating in or initiating reentry. It is popularly held that the structure of the Purkinje network is fractal, to maximize signal transmittance in a limited volume. But closer examination shows that this is not the case, and incorporation of a fractal network into computer models to simulate the cause of fibrillation could yield a different result than a network that incorporates loop structures.