For the first time, researchers have controlled the pace of an embryonic heart using pulses of light. The new method is a leap forward for cardiologists and developmental biologists, who hope it will help yield a better understanding of heart development and congenital heart disease. They also hope the development could eventually lead to new types of optical pacemakers.
Artificial pacemakers normally use electrodes to deliver regular, “paced” electrical impulses to the heart muscle to keep its beats consistent. While the devices are safe in the short term, they can cause damage to the muscle if used over decades. The technique’s intrusive methods–which require contact with the heart –also limit its capabilities as a research tool.
“If you’re trying to use an electrode to touch the heart and stimulate it, the contacts could disrupt potential observation of the heartbeat,” says Ed Boyden, a professor of biological engineering at MIT. Boyden was not involved in the research. “A noninvasive methodology for pulsing the heart is important for science. Potentially, this could open up a lot of experiments.”
The idea of controlling cells with light is not new: Some labs have shown that neurons can be turned on and off with optical stimulation, and one group has used powerful laser pulses to pace cardiac cells in culture. But this is the first time that an entire heart in a live animal has been paced with light.
In the new technique, described today in the journal Nature Photonics, scientists placed an infrared laser fiber one millimeter above the developing hearts of two-day-old quail embryos. As they changed the pace of the laser pulses, the heartbeat shifted to match. “Noninvasively pacing a heart with light has different advantages and disadvantages from electrical stimulation,” says Michael Jenkins, a postdoc in bioengineering at Case Western Reserve University in Cleveland, and the study’s first author. “It has the potential to be used all the way from basic research to clinical applications.”
Jenkins and his colleagues are working on optical pacing of adult quail hearts now, using the same technique of threading an optic fiber into their bodies so that they are next to the heart. But the tissues are more opaque than those found in embryos, making light penetration more difficult. Because the adult quails are larger, it’s also more difficult to find precisely the right spot on which to train the light.
Scientists hope that this type of nonintrusive method can help uncover more about cardiac development and the unknown causes of congenital heart disease. “We can use it to noninvasively study how environmental changes that change the heart rate might lead to heart defects,” Jenkins says. “Or to study how changes in the heart rate during crucial stages of growth might change gene expression.”
Jenkins can’t yet explain how the light causes the heart muscle to contract, and says that it may take years to figure this out. But he thinks it may be that the infrared wavelengths are heating up the cells, somehow changing the ability of a particular set of ion channels to transmit a charge.
Douglas Cowan, an assistant professor at Children’s Hospital in Boston, has been working on a different method for stimulating heart muscle function, one based on tissue engineering. He posits that Jenkins’s approach might help nudge stem cells to differentiate into beating cardiac cells.
Because light waves can’t get through more than a few layers of tissue, the researchers suggest that, in humans, their technique might be particularly useful for pacing an exposed heart during surgery.
Beyond that, an implanted optical pacemaker–while still a far-off prospect–is an idea that many researchers believe is worth pursuing. “In kids, electric pacing for 15 or 20 years causes the heart not to develop so well,” Jenkins says. While this is less worrying for a 75-year-old, it can be a big concern for a pediatrician who’s putting a pacemaker into a three-year-old. “If optical pacing were able to pace the heart in such a way that it beats more intrinsically, that could be an advantage,” he says.