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Heterogeneities are required parts of systems. However, extreme
differences are often the hallmark of a disease. We need to understand
what promotes these extremes and the implications of such extremes.
This goal requires the work of many people working on many different
processes... a heterogeneity of science if you will.
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Regional Ventricular Heterogeneities
In order to better
understand the results of remodeling that occurs in disease states, we must
first understand the differences that make up the entire system. For a long
time, the left ventricle has been the focus of much study because it is the
ventricle which provides systemic circulation. However, the right ventricle
has many unique properties which suggest that it may be as important for understanding where arrhythmias originate. To that end,
this project looks at all areas of both ventricles from the apex to base,
left to right, anterior to posterior, and epicardium to endocardium.
The two projects for
studying interventricular heterogeneities are:
Andersen-Tawil Syndrome-1 (ATS1). ATS1 in humans is characterized by
frequent non-sustained runs of bi-directional VT. We have recreated this
phenomenon in a guinea pig drug induced model of ATS1. Importantly, the
originating beats arise from specific regions of the heart. The purpose of
these studies is to understand the calcium regulatory mechanisms underlying
this regionally preferential manifestation of these arrhythmic beats.
The Connexin-Conduction Relationship. In guinea pig, right ventricular
tissue conducts electrical impulses from cell to cell faster than the left
ventricle despite a lower protein concentration of the principal gap
junction protein connexin43. This project explores this apparently
paradoxical finding.
Current Voltage Spectroscopy
Ion channels can be modeled as simple resistor capacitor
networks. The purpose of the model is to predict many behaviors as
simplistically as possible. However, we may gain further insights into ion
channel behavior if we remember that ion movement through a channel is a
very dynamic process that includes more than a single value for the
conductance of an ion across the membrane. New studies tell us that the
method by which an ion moves through the protein channel is a highly
regulated process where the ion usually goes through an elaborate route
dictated by amino-acid locations. This suggests that each process may be
governed by different rate constants and the overall measure of
transmembrane conductance may be only a very small part of the picture and
our understanding. To understand these differences, we are measuring the
response to transmembrane conductance in the presence of specific electric
field frequencies hoping to better understand the differences between ion
channel conductances. The end goal of this work is to be able to measure the
individual contributions of ion channels to the action potential in real
time.
Non-traditional Bioelectric Mapping
Current methods for measuring electrical potentials in
excitable tissue include microelectrode recordings, optical mapping with
voltage sensitive dyes, and needle recordings. Microelectrode recordings are
considered the gold standard for measuring the transmembrane potential of a
single cell. However, it is difficult to have many stable microelectrode
recordings for the billions of myocytes that make up a heart. Optical
mapping with voltage sensitive dyes allows one to measure the transmembrane
potential over an average area of tissue. However, the average signal comes
from a group of myocytes, can only be measured from a 2-D surface, and is
complicated by optical phenomenon. A needle electrode can have multiple
electrodes at fixed distances which can be pushed into the depth of the
heart. However, these electrodes measure electric fields instead of
transmembrane potential. Furthermore, data generation is difficult because
the spatial orientation of the needles is time consuming to quantify. There
is also a concern that plunging electrodes through tissue may generate some
type of injury response in the tissue. We are investigating alternative
minimally invasive methods for measuring bio-electric phenomenon in 3-D.
BIOEN 1101: Introduction to Biomedical Engineering
BIOEN 3202: Physiology for Engineers
BIOEN 6460: Electrophysiology and Bioelectricity of Tissues
BIOEN 6464: Contemporary Topics in Cardiac Electrophysiology
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Steven Poelzing, Ph.D. Research Assistant Professor of Bioengineering University of Utah Cardiovascular Research and Training Institute 95 South 2000 East, Room 233 Salt Lake City, Utah 84112-5000 Phone: 801-585-1862 |
