Abstract:
In this thesis, mathematical modelling, instrumentation development and experimental
studies are combined to effect two advances in the study of cardiac electrophysiology.
Firstly, we outline a method that will enable microstructural information gathered using
extended confocal microscopy to be incorporated into whole heart models of electrical
propagation. A structured finite element technique is used to solve the bidomain
equations on a realistic representation of myocardial architecture. The effects of
intercellular gaps in the tissue on electrical propagation, and the response of myocardium
to defibrillation-strength shocks, are examined. It is shown that myocardium is not a
transversely isotropic electrical medium as has been widely assumed. Instead it is most
appropriately viewed as orthotropic, with different electrical properties assigned to three
microstructurally defined orthogonal axes. It is also concluded that the intercellular
tissue gaps provide a likely mechanism for activation of a critical volume of tissue during
defibrillation.
Secondly, a novel imaging system is presented which enables transmembrane potentials
to be recorded simultaneously at multiple sites through the heart wall. While heart surface
optical recordings of transmembrane potential have been widely used in studies of normal
and pathological heart rhythms, it is difficult to obtain information about propagation
processes deep within the heart wall. A probe constructed from optical fibers is used to
deliver excitation light to and collect fluorescence from 6 tissue sites each spaced 1mm
apart. For individual channels, excitation is provided by the 488nm line of a watercooled
argon-ion laser, while the fluorescence of a voltage-sensitive dye is split at 600nm
and imaged into separate photodiodes for later signal ratioing. The system has been
sucessfully used to record intramural action potentials in the isolated rabbit heart and is
designed to be easily expandable to accommodate multiple optical probes. The
fluorescence collection volume of the fibre-optic probe has been characterised in
rhodamine solution using two-photon microscopy. These data are compared with
corresponding results obtained with two flat cleaved optical fibres in solution and in
stained heart tissue. The results demonstrate that the effective collection depth in cardiac tissue for our optrodes was 100μm, but that this is dependent on the type of optical fibre
used to fabricate the optrode.
These techniques developed in this research provide a basis for more systematic study of
the initiation and termination of reentrant electrical activity in the heart. Future research
that builds on the original findings presented in this thesis is discussed.