For people who suffer from a rapid heartbeat condition
called tachycardia, an implanted device can usually nudge
the racing blood pump back into a normal rhythm by applying
electrical pulses to the heart. But on rare occasions, in a
twist that has baffled physicians, the anti-tachycardia
pulses produce the opposite effect: They trigger an even
faster and more dangerous heartbeat.
By electrically jolting cardiac cells in a lab and
mapping the change in the electrical activity, biomedical
engineers at Johns Hopkins may have found an answer to this
mystery. Writing in the Oct. 26 edition of Proceedings
of the National Academy of Sciences, the researchers
proposed that maverick electrical waves called multiarm
spirals might be causing the accelerated heartbeats.
The findings could lead to improvements in the next
generation of implantable cardioverter defibrillators,
devices used by tens of thousands of people with heart
rhythm abnormalities. "At present, the devices can be
programmed by the physician to deliver any one of many
different combinations of pulse parameters, and although
standard algorithms exist, the optimum algorithm is not
known," said Leslie Tung, a co-author of the paper and
director of the lab in which the research was conducted.
Tung is an associate professor in the Whiting School's
Department of Biomedical
Engineering.
"When the condition called ventricular tachycardia is
accelerated to the point where it becomes indistinguishable
from ventricular fibrillation, the patient must now receive
a powerful, painful shock to restore normal rhythm, a
scenario that is best avoided," said lead author Nenad
Bursac, who worked on the research as a postdoctoral fellow
in Tung's lab. "We are the first to show that these
multiarm spiral waves can be electrically induced in sheets
of cardiac cells, and we think that implanted devices could
sometimes be setting off the same pattern in the heart."
Tung's lab is one of the few in the world that studies
electrical activity in large-scale cardiac cell cultures.
The Johns Hopkins researchers collect ventricular cells
from newborn rats and remove the connective tissue. The
remaining cardiac cells are placed in a nutrient solution,
where they thrive and establish electrical connections with
one another. The result is a roughly circular single-cell
layer of cardiac cells, about 2 centimeters in diameter,
situated atop a microscope cover slip.
For the experiments in their new study, Tung's team
stained the cells with a voltage-sensitive dye. The
researchers then used the tip of a platinum wire to
administer electric pulses to the cell culture. Within
milliseconds of each jolt, a wave of electrical activity
moved through the culture, causing the stained cells to
glow as it passed through them. An optical-fiber bundle
beneath the culture captured this light show, enabling the
researchers to see the shape and movement of each
electrical wave as it passed through the cardiac cells.
This gave the researchers a glimpse into the type of
electrical activity that takes place in the heart. In a
healthy organ, these waves move smoothly through the
cardiac cells, causing the muscle fibers to contract and
pump blood in a coordinated manner, like soldiers marching
in near lockstep. During ventricular tachycardia, however,
electrical waves can often form in the shape of a
single-arm spiral, throwing the cellular soldiers out of
sync and into a very fast but inefficient rhythm that
results in a weakened pump output. Implanted devices can
deliver a series of electrical pulses to disrupt these
errant waves and restore a normal heartbeat.
The Johns Hopkins researchers found that the same kind
of spiral wave behavior could be reproduced in their cell
cultures, making the spiral waves available for scrutiny.
Just as is the case with implanted devices, when electrical
pulses were administered to single-arm spirals, the waves
were not always halted. Instead, they broke up into a new
pattern called multiarm spirals, exhibiting complex wave
dynamics and an accelerated rhythm. The researchers
hypothesize that what they witnessed in the lab may mirror
what happens when an implanted device inadvertently
triggers an accelerated heartbeat. "The basic rules on how
waves propagate and respond to electrical stimuli may best
be learned in simplified models of the heart," Tung said.
"With further research, it may be possible to evaluate and
optimize different anti-tachycardia algorithms."
Funding for this research was provided by the
Mid-Atlantic Affiliate of the American Heart Association
and the National Institutes of Health.
Bursac, the lead author of the study, is now an
assistant professor of biomedical engineering at Duke
University. Felipe Aguel, a co-author of the study, was a
postdoctoral fellow in Tung's lab when the research was
conducted. He is now a staff fellow with the U.S. Food and
Drug Administration.
Related Web Site
Leslie Tung's Cardiac Bioelectric Systems Lab
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