The Heart Is a Suction Pumper
A. Forouhar, et. al., Science, vol. 312, pp. 751–753. © 2006, American Association for the Advancement of Science.
A 3-D reconstruction of a 26-hour-old zebrafish embryo’s heart tube. The glowing red cells are the myocytes, and the three-dimensional trajectory traced by the center of each cell (colored dots) over two successive heartbeats has been drawn in as well. The inflow tract is at the bottom, and the red double-headed arrow shows where the “pacemaker” cells are located. The 3-D scale bar at lower left corner is 20 microns, or millionths of a meter, along each leg.
Looking at an adult human heart and an embryo’s
heart, you’d never guess that the former developed from the latter.
While the adult heart is a fist-shaped organ with chambers and valves,
the embryo heart is tubular. It’s been assumed that the embryonic
heart pumps by peristalsis, like your intestines do—a method of
action similar to squeezing a tube of toothpaste. But Caltech biologists
and engineers leading an international team have shown that the tube is
actually a suction pump that works much like the left ventricle in the
mature heart.
Says Mory Gharib (PhD ’83), Caltech’s Liepmann
Professor of Aeronautics and professor of bioengineering, “Embryonic
and adult hearts look like two different engineers designed them separately.
But this study shows there is continuity to the pumping mechanism.”
Gharib’s graduate student Arian Forouhar (PhD ’06)
and the other researchers used confocal microscopes in the Biological
Imaging Resource Center (BIRC) located in Caltech’s Beckman Institute
to do time-lapse photography of embryonic zebrafish. Zebra-fish were chosen
because they are essentially transparent, thus allowing for easy viewing,
and because they develop completely in only a few days.
Scott Fraser, Caltech’s Rosen Professor of Biology
and professor of bioengineering and the principal investigator of the
BIRC, notes that “this pumping mechanism had not been noticed before
because of the limitations of imaging technology. Now we have a device
that is 100 times faster than the old microscopes, allowing us to see
things that previously would have been a blur. Now we can see the motion
of blood and the motions of cardiac walls at very high resolutions.”
The time-lapse photography showed that the embryo heart uses a valveless pumping action known as hydroelastic impedance pumping, in which a handful of cells called myocytes, usually situated near the entrance of the heart tube, contract to initiate a series of forward-traveling elastic waves that eventually reflect back from the tube’s far end. At a specific range of contraction frequencies, these waves constructively interfere with one another to generate an efficient dynamic-suction region at the tube’s outflow tract. This mode of action is also noteworthy because a small number of “pacemaker” cells are sufficient to sustain circulation.
A. Forouhar, et. al., Science, vol. 312, pp. 751–753. © 2006, American Association for the Advancement of Science.
Above,
A: In this set of six 3-D reconstructions during a single heartbeat, the
myocytes appear as white blobs, and the yellow lines mark the heart wall,
or endocardium. The grid size is 20 microns. B: The red and blue arrows
show the paths of the wave fronts as they spread out from the contraction
site. Changes in heart-tube diameter and elasticity at the inflow tract
(ift) and outflow tract (oft) reflect the waves back on themselves to
form the low-pressure zone that pumps the blood. Elapsed times are shown
in
milliseconds.
“The heart is one of the few things that makes itself
while it’s working,” Fraser says. “It likely begins
forming its structures when it’s still a tiny tube the diameter
of a hair.” “This allows us to reconsider how embryonic cardiac
mechanics may lead to anomalies in the adult heart, since impairment of
diastolic suction is common in congestive heart-failure patients,”
says Gharib. “One of the most intriguing features of this model
is that the mechanical stimuli from only a few contractile cells may guide
later stages of heart development,” says Forouhar.
According to Gharib, this simplicity of construction could
guide the design of devices to gently move blood, drugs, or other biological
fluids. The findings could also lead to new treatments of heart diseases
that arise from congenital defects, and, says Fraser, demonstrate the
promise of advanced biological imaging techniques for the future of medicine.
The work is described in the May 5 issue of Science. In addition to Forouhar, Gharib, and Fraser, the authors are Michael Liebling, a postdoc in the BIRC; bioengineering grad students Anna Hickerson (BS ’00, PhD ’05) and Abbas Nasiraei Moghaddam; Huai-Jen Tsai of National Taiwan University’s Institute of Molecular and Cellular Biology; Jay Hove of the University of Cincinnati’s Genome Research Institute; and Mary Dickinson of the Baylor College of Medicine. —RT
