Biomedical Engineering Reference
In-Depth Information
HCN212 has faster activation/deactivation kinetics. Different HCN channels were
expressed in heart cells. Channel parameters and the effect on spontaneous rate
were measured, and the channel parameters were entered into a computer simula-
tion to explore their contribution to the rate effect. The biological pacemaker
appears to respond to the body's signals in the same manner as the heart's native
pacemaker, yet it requires no batteries or replacement of electrical stimulator leads,
and could last a lifetime. These results illustrate the benefit of screening HCN con-
structs in spontaneously active myocyte cultures and may provide the basis for
future optimization of HCN-based biological pacemakers for cardiac arrhythmias.
In addition, the HCN-expressing heart culture system could serve as a screening
assay for new pharmacological agents to regulate heart rate.
Ventricular Tachycardia
Ventricular tachycardia (VT) refers to a rapid heartbeat originating in the ventricles,
where the rate is anywhere from 100 to 250 beats per minute. VT is usually the
result of serious damage to the heart muscle, although it occasionally occurs in
healthy individuals. Patients at the highest risk for VT are commonly treated with
implantable defibrillators. Such patients also require the use of antiarrhythmia
drugs in the chronic management of VT as a result of the patient's discomfort
resulting from the shocks associated with the firing of the defibrillators. Bioheart is
developing MyoCell VT
™
, a cell-based product that can provide VT patients with
a normalized heart function, to accomplish these objectives.
The proteins responsible for the cardiac cell to cell communication and the for-
mation of intercalated disks and gap junctions are Cx 43 and N-Cadherin.
Dr. Charles Murry, University of Washington, a Bioheart collaborator, has published
on the ability of myoblasts to express Cx 43 and N-Cadherin in vitro. By injecting
genetically modified myoblasts that have the ability to electromechanically couple
in the area of VT block, an “electrical bridge” across the VT block can be estab-
lished and therefore restore normal electrical conduction pathways within the heart.
Current research is focused on in vivo models for simulating the overexpression of
Cx 43 and N-Cadherin in preclinical settings and alleviating the conduction block-
ages that form VT.
Prevention of Myoblast-Induced Arrhythmias
by Genetic Engineering
Skeletal myoblasts are an attractive cell type for transplantation because they are
autologous and resistant to ischemia. However, clinical trials of myoblast transplanta-
tion in heart failure have been plagued by ventricular tachyarrhythmias and sudden
cardiac death. Previous research from animal transplants showed that heart tissue
regrowth produced a mix of skeletal and heart muscle. The pathogenesis of arrhyth-
mias following myoblast transplant is poorly understood, but may be related to the
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