Cardiac catheterization is a technology first conceived in 1929 and implemented in clinical practice starting in the 1940s. Initially a diagnostic tool, catheters (thin tubes) were inserted into a vein or artery in the arm or leg and threaded guided by x-ray into close proximity to or inside the heart. Using contrast dye injected into the heart and blood vessels through the catheter, doctors were able to see their structure two-dimensionally. This was revolutionary for diagnosis.

But in the 1960s catheterizations evolved beyond diagnosis and became useful as a compliment to surgery. Doctors started using them to change the internal blood flow. A catheter could poke a hole where needed. Or it could be used to carefully open a blood vessel. But this really didn’t get going until the 1970s when catheters with inflatable balloons were first used to open blocked coronary arteries. By the 1990s interventional catheterizations were common practice in hospitals around the world.

Devices of all kinds from stents (little wire mesh structures that could be embedded in blood vessel walls) to patches were among the many tools that doctors could now insert into patients. No need to cut open the patient. In the case of my daughter’s last procedure she received a pulmonary valve that was inside a stent. When implanted through a balloon catheter the stent was opened up and with it the bovine valve. It meant she could avoid another open heart surgical procedure. It’s now six years and she’s been going strong with her new valve.

But it gets even better. In the last month researchers at Boston Children’s Hospital and the Wyss Institute of Harvard University announced the next generation of catheterization technology, a specialized catheter for repairing holes in the heart using biodegradable adhesive patches. Their research is reported in an article entitled, “A light-reflecting balloon catheter for atraumatic tissue defect repair,” in the September 23, 2015 issue of Science Translational Medicine. The new catheter and adhesive features several innovations. The former features a balloon with a highly reflective surface and an ultraviolet pinpoint light source that can be directed to a a specific site. The latter a patch containing a biodegradable adhesive coating.

During a procedure such as the closing of a septal defect (a hole in the heart wall separating the organ’s pumping chambers), the catheter tip is directed to the repair site. The patch is deployed and the ultraviolet light source is switched on. The light reflects off the balloon surface. This activates the adhesive coating in the patch. The glue then cures. The balloon is deflated and the catheter is removed. The patch takes less than five minutes to cure. The four images below illustrate the procedure. The upper left shows the catheter insertion. The upper right the deployment of the balloon on one side of the hole. The lower left shows the adhesive patch being deployed and bathed in ultraviolet light to cure it. The lower right shows the patch after removal of the catheter.

The remarkable, light-activated adhesive agent is a product of Gecko Biomedical. It is highly viscous and hydrophobic making it capable of working in wet environments such as the inside of a blood-filled beating heart. Fully biodegradable and elastic so it conforms to the tissue surface to which it adheres, and once in place the patch gets replaced by the body’s own cells which grow over it as it dissolves. The biodegradable rate is adjustable for patches that need to be in place for a longer period of time to ensure viability of the repair. In the end the heart is left with no foreign materials that can become places where bacteria can collect leading to endocarditis (inflammation of the lining of the heart).

“This really is a completely new platform for closing wounds or holes anywhere in the body,” states Conor Walsh, Assistant Professor of Mechanical and Biomedical Engineering, Harvard Biodesign Lab. The potential for the technology’s use in repairing internal wounds goes far beyond cardiology. The variable rate of biodegradability makes the adhesive patch usable for all kinds of procedures. As for cardiology the technology is revolutionary, further extending the use of minimally invasive procedures to replace complicated open heart surgery which usually involves stopping a beating heart and going on bypass machines to maintain life support.

Researchers at Boston Children’s Hospital, however,  have been experimenting with a new way of delivering oxygen to the blood using microscopic nanobubbles of oxygen encased in a foamy lipid suspension that releases the gas directly when injected like a vaccine. In the image below you can see one of the microscopic nanobubbles in yellow, adjacent to some red blood cells.

So far the test subjects, rabbits with obstructed airways, have remained alive and stable without taking a breath for 15 minutes. The results of this research have been published in the journal, Science Translational Medicine. What does this mean for victims suffering from pneumonia, a heart attack, stroke, asthma, drowning or airway injuries? When administered the microscopic bubble infusion temporarily stops the hypoxemia, which can give a medical trauma team the opportunity to restore airway or lung function. From rabbits to larger animal trials and finally human clinical trials, we may soon see this discovery become a regular part of CPR and emergency medical procedures, saving countless lives.

The current maximum time of use for microscopic nanobubble injections is 30 minutes with serum volume being the limiting factor. The researchers, however, are working on increasing the ratio of microscopic bubbles to fluid to extend the therapy.

For those of you who know me, CHD is a subject near and dear to me because of my daughter. She was born with a rare heart lesion and has had multiple surgical corrections throughout her life. That’s one of the reasons I have been studying and writing about biomedicine for so many years.

The new procedure comes from one of the hotbed facilities doing CHD research, Boston Children’s Hospital in Boston Massachusetts. The surgeons and cardiologists there have been working to find a way to let the body help itself in repairing the rare condition known as Hypoplastic Left Heart Syndrome (HLHS) seen in the image below.

Children born with this defect suffer from an underdeveloped, almost non-existent left-ventricle. Normally that venticle serves as the major pumping chamber of the heart pushing blood through the aorta to the rest of the body. But in HLHS children the chamber is malformed. When the child is in utero the condition is not life threatening. But once born HLHS without intervention is a death sentence. HLHS is very rare with maybe 1,000 children born in the United States and 100 in Canada each year. Early surgical intervention is the only chance these children have for surviving days let alone weeks, months or years.

When a HLHS baby is born they are immediately compromised. Early intervention attempts to keep the holes that exist in utero between the major blood vessels and the two upper chambers of the heart open. Normally these close within a few hours after birth. With the holes open there is at least some circulation of blood to the body’s major organs.

Surgical intervention prior to this new protocol has involved creating temporary fixes. The first is called the Norwood Procedure which turns the right ventricle used to pump blood to the lungs into a single pumping chamber pumping blood to both the lungs and the rest of the body. Using the right ventricle this way has drawbacks. The right side of the heart is less muscular than the left because the circulatory demands on it are far less than the left. In turning it into a dual-purpose pumping chamber the muscle gets highly stressed and eventually fails. That’s because there isn’t enough muscle to do both jobs.

If a child survives for a period of time after a Norwood then other procedures can be done to try and create as close to a permanent fix as possible. But ultimately the preferred treatment for any HLHS child is to find a donor heart. Transplantation comes with its own challenges including donor availability and rejection management and therefore is considered a last resort. Surgeons would far prefer to use a body’s original parts whenever possible to affect a cure. That’s why finding a way for the body to self heal is considered ideal.

So the team at Boston Children’s set out to do just that, find a way to stimulate the left ventricle to grow from its hypoplastic state to a near normal size. Their newly developed surgical protocol is a technique that involves directing blood not away from but to the underdeveloped left ventricle and by doing this triggering the ventricle to grow so that it can eventually assume its normal function.The doctors who have pioneered this technique recently reported preliminary results in the Journal of the American College of Cardiology. They selected 34 patients for the new procedure and reported that 12 of them now have two working ventricles.

What’s involved with the protocol? Multiple surgical interventions. The first procedure alters the circulation of blood in and around the heart to stimulate left ventricle growth. Secondary procedures follow to repair or replace malformed or occluded heart valves, close off any holes between the pumping chambers, and reduce the amount of inelastic tissue in and surrounding the heart so that it can pump more efficiently.

Considering past results, even with multiple surgical procedures, this new protocol should give HLHS children a fighting chance at a full life.