Biomedical Engineering Reference
In-Depth Information
pacemaker and follower cells but, if the load is excessive, it may arrest the pacemaker
by clamping pacemaker cells to hyperpolarized resting membrane potentials. The SA
node has special means to circumvent this problem, including expression of an
hyperpolarization-activated depolarizing current (
I
f
) [10] and a complex architecture
of the node atrium interface [1, 6]. In the case of bio-pacemakers, the interface
architecture can be hardly controlled; thus, for their development, prediction of the
interplay between polarizing and depolarizing currents and quantitative estimates of
the required generator size may be necessary. As reviewed by Wilders in this issue
[14], accurate computer models of the SA node activity, now available, may help in
understanding how depolarizing and repolarizing currents interact and respond to
perturbing conditions. The problem of the match between generator and load is
illustrated in this issue by Joyner et al. [6]. These investigators addressed this problem
with a mixed approach in which SA electrical activity, generated by a numerical
model, was electrically coupled through a variable resistor to a real atrial myocyte.
This allowed to test how coupling resistance may affect the pacemaker load
interaction and to obtain a quantitative evaluation of the conditions required for
propagated pacemaking [6].
As highlighted in this issue, research in the field of bio-pacemaking is blooming.
Nonetheless, in light of the performance and safety of the electronic pacemakers now
available, development of a better alternative is an extremely demanding task. It yet
has to be proven that the bio-pacemaker surpasses its electronic counterpart with
regard to adaptability to physiological requirements of the body and longevity. While
potentially effective pacemaking strategies have been identified, the development of
genetic engineering methods suitable to implement them with safety and stability
remain a considerable challenge. The possibility of uncontrolled gene expression,
carcinogenic risk of viral vectors affording stable transduction and immune rejection
of implants are among the problems that need to be solved before bio-pacemaking can
be considered for clinical use. Moreover, ventricular resynchronization, a major
advancement of artificial pacemaking, may be difficult to achieve with bio-
pacemakers.
Despite these concerns, bio-pacemaking seems more easily achievable than other
potential applications of cardiac cell therapy. This is because bio-pacemaking aims to
restore a single function with a well-defined mechanism, it requires myocardial
homing of a limited number of cells and a localized intervention. Development of bio-
pacemakers may be an ideal challenge for the approach typical of bioengineering,
based on a close interaction between expertise in biophysics, molecular and cell
biology.
References
1.
Anghel TM, Pogwizd SM (2006) Creating a cardiac pacemaker by gene therapy. Med Biol
Eng Comput 45:145-155
2.
de Boer TP, van Veen TA, Houtman MJ, Jansen JA, van Amersfoorth SC, Doevendans
PA, Vos MA, van der Heyden MA (2006) Inhibition of cardiomyocyte automaticity by
electrotonic application of inward rectifier current from Kir2.1 expressing cells. Med Biol
Eng Comput 44:537-542
