For decades, cardiac researcher James McCully, PhD, has been spellbound by the idea of using mitochondria, the “batteries” of the body’s cells, as a therapy to boost heart function. Finally, a clinical trial at Boston Children’s Hospital is bringing his vision — a therapy called mitochondrial transplantation — to life.
Mitochondria, small structures inside all of our cells, synthesize the essential energy that our cells need to function. In the field of cardiac surgery, a well-known condition called ischemia often damages mitochondria and its mitochondrial DNA inside the heart’s muscle cells, causing the heart to weaken and pump blood less efficiently. Ischemia, a condition of reduced or restricted blood flow, can be caused by congenital heart defects, coronary artery disease and cardiac arrest.
For the smallest and most vulnerable patients who are born with severe heart defects, a heart-lung bypass machine called extracorporeal membrane oxygenation (ECMO) can help restore blood flow and oxygenation to the heart. But even after blood flow has returned, the mitochondria and their DNA remain damaged.
“In the very young and the very old, especially, their hearts are not able to bounce back,” says McCully.
Ischemia can be fatal for the tiniest patients
After cardiac arrest, for instance, a child’s mortality rate jumps to above 40 percent because of ischemia’s effects on mitochondria. If a child’s heart is too weak to function without the support of ECMO, his or her risk of dying increases each additional day spent connected to the machine.
But what if healthy mitochondria could come to the rescue and replace the damaged ones? …
Soft robotic actuators, which are pneumatic artificial muscles designed and programmed to perform lifelike motions, have recently emerged as an attractive alternative to more rigid components that have conventionally been used in biomedical devices. In fact, earlier this year, a Boston Children’s Hospital team revealed a proof-of-concept soft robotic sleeve that could support the function of a failing heart.
Despite this promising innovation, the team recognized that many pediatric heart patients have more one-sided congenital heart conditions. These patients are not experiencing failure of the entire heart — instead, congenital conditions have caused disease in either the heart’s right or left ventricle, but not both.
“We set out to develop new technology that would help one diseased ventricle, when the patient is in isolated left or right heart failure, pull blood into the chamber and then effectively pump it into the circulatory system,” says Nikolay Vasilyev, MD, a researcher in cardiac surgery at Boston Children’s.
Now, Vasilyev and his collaborators — researchers from Boston Children’s, the Harvard John A. Paulson School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering at Harvard University — have revealed their soft robotic solution. They describe their system in a paper published online in Science Robotics today. …
Medical implants can save lives by correcting structural defects in the heart and other organs. But until now, the use of medical implants in children has been complicated by the fact that fixed-size implants cannot expand in tune with a child’s natural growth.
To address this unmet surgical need, a team of researchers from Boston Children’s Hospital and Brigham and Women’s Hospital have developed a growth-accommodating implant designed for use in a cardiac surgical procedure called a valve annuloplasty, which repairs leaking mitral and tricuspid valves in the heart. The innovation was reported today in Nature Biomedical Engineering. …
About 1 out of 100 babies are born with a congenital heart defects. Thanks to medical and surgical advances, these children usually survive into adulthood, but they are often left with developmental, behavioral or learning challenges.
Children with “single-ventricle” defects — in which one of the heart’s two pumping chambers is too small or weak to function properly — are especially at risk for neurodevelopmental problems. “Single-ventricle physiology creates cerebrovascular hemodynamics that can reduce oxygen delivery to the brain,” explains Jane Newburger, MD, MPH, director of the Cardiac Neurodevelopmental Program at Boston Children’s Hospital.
How does this play out in adolescence? In three recent studies, Boston Children’s Heart Center collaborated with the departments of Neurology and Psychiatry to track neurodevelopmental outcomes after corrective Fontan operations. They evaluated preteens and teens as old as 19 — the longest follow-up to date. …
In 1962, the Harvard School of Public Health made a critical loan to Boston Children’s Hospital: the Harvard hyperbaric chamber. It established a new approach to pediatric heart surgery at Boston Children’s.
For many children — including a premature infant named Janet, born in 1964 with a heart murmur — the hyperbaric chamber would prove to be life-saving.
At that time, before the invention of the heart-lung bypass machine, hyperbaric chambers offered a way to operate on infants more safely. That’s because hyperbaric oxygenation, coupled with the effects of increased pressure on the respiratory system, seemed to give infants a better chance of surviving heart surgery. …
Developing a child-centric approach to treating heart failure is no easy task. For one thing, the underlying causes of decreased cardiac function in children vastly differ from those in adults. While most adults with heart failure have suffered a heart attack, heart failure in children is more likely the result of congenital heart disease (CHD), or a structural defect present at birth that impairs heart function. And most therapies designed for adults haven’t proven equally effective in children.
Reporting in the April 1 Science Translational Medicine, Brian Polizzotti, PhD, and Bernhard Kuhn, MD, demonstrate that not only does the drug neuregulin trigger heart cell regeneration and improve overall heart function in newborn mice, but its effects are most potent for humans within the first six months of life. …
When a patient needs a cardiac intervention, surgeons can choose to access the heart in one of two ways: open-heart surgery or a cardiac catheterization.
Open-heart surgery offers clear and direct access to the heart, but it also requires stopping the heart, draining the blood, and putting the patient on an external heart and lung machine. Catheterization—insertion of a thin, flexible tube through the patient’s groin and up into the still-beating heart—is less invasive. But it’s not suitable for very complicated situations, because it is hard to manipulate the heart tissue with catheter-based tools from such a far distance.
Both methods have been highly optimized, but each has its own risks, benefits and drawbacks. Wouldn’t it be nice if there were a way to directly access the heart and maintain normal heart function and blood flow while repairs are performed?
A safe and effective adhesive, or glue, that can be used internally in the body has been a pressing need in medicine. Its creation has faced major hurdles—not the least of which is ensuring the glue is nontoxic and capable of repelling fluids—but a new study published today in Science Translational Medicine offers a potential breakthrough.
Congenital heart defects occur in nearly 1 in 100 births, and those that require treatment are plagued with multiple surgeries to deliver or replace implants that do not grow along with the child. Currently, therapies are invasive and challenging due to an inability to quickly and safely secure devices inside the heart. Sutures take too much time to stitch and can cause stress on fragile heart tissue, and the available clinical adhesives are subpar.
“Current glues are either toxic or easily wash out in the presence of blood or react immediately upon contacting water,” says Pedro del Nido, MD, chief of Cardiac Surgery at Boston Children’s Hospital and senior co-author of the study. “The available options also tend to lose their sticking power in the presence of blood or under dynamic conditions, such as in a beating heart.” …
The new strategy, called staged left ventricle recruitment (SLVR), seeks to harness a child’s native capacity for growth and healing to encourage the undersized left ventricle to grow, giving the child a fully functional heart.
The human heart is kind of like a busy factory with two powerful pumps—the ventricles—and two “unloading docks,” called the atria. Together, these chambers maintain a delicate balance, ensuring that oxygen-rich blood moves out into the body and that oxygen-poor blood gets pushed back to the heart and lungs.
Just like any factory, however, the heart’s essential functions can be seriously disrupted if just one piece of machinery isn’t working properly.
The mitral valve is a key part of that mechanical balance. This one-way valve helps move blood from the left atrium into the left ventricle, which then pushes the blood out to the body. A failure of the valve can be life-threatening, but fixing or replacing it in children is incredibly complex—and often requires many repeat operations over time.
But two cardiac surgeons at Boston Children’s Hospital, Sitaram Emani, MD, and Pedro del Nido, MD, may have made the repair a little easier by developing a replacement mitral valve that can expand as a child grows. …