Research selected as 'world changing idea'

by Dawn Brazell
Public Relations

The parents he meets know him as their child's anesthesiologist at MUSC Children's Hospital. Others may recognize him from TV and print ad campaigns where he's dressed in a monkey towel blowing bubbles with children.

Dr. Frank McGowan as seen on commercials that ran promoting MUSC's Children's Hospital.

But there's yet another side to Frank McGowan, M.D., who collaborates with researchers at Boston Children's Hospital in Massachusetts on a new technique heralded as a potential medical breakthrough. The team has developed microparticle-based oxygen-delivery technology that oxygenates the blood and bypasses the lungs. It has the potential of saving lives for a wide array of patients and conditions, from wounded veterans in the field to premature babies in intensive care units.

The research landed on the cover of the December issue of Scientific American as one of 10 "world changing ideas." It also was the cover of the journal Science Translational Medicine in June 2012 with its successful use in an animal model. McGowan said the possibilities of promising clinical applications will keep researchers busy for many years to come.

Dr. Frank McGowan holds up the December issue of Scientific American that selected the research he and Boston colleagues are doing as a world-changing idea.

The idea first came up five years ago when McGowan worked at Boston Children's Hospital. A doctor in residence, John Kheir, M.D., asked how he could have saved a patient he lost because of an inability to quickly oxygenate her blood. "We started thinking why don't we have better ways to acutely deal with this while we're trying to figure out what we're going to do longer term."

Then Kheir and McGowan began to do more than talk.

The challenge was to devise some kind of shell to safely encase and deliver oxygen in the blood so that it could release the encapsulated oxygen to deoxygenated blood and then collapse in a non-toxic form to be eliminated from the body.
"We found that there are materials that can do that with shells made of lipid or mixtures of fats and other substances, many of which are normally found in the body," McGowan said. "We found a number of really smart people who had spent their lives trying to figure out how to encase various substances, biologic drugs, viruses, genes and other things in lipids and other compounds. There's always a whole world out there when you go looking."

McGowan said the research is the perfect example of why basic science research is needed. "There was a tipping point. People had devoted careers doing fundamental work in related areas for many reasons and applications. We were able to study and theorize based upon it. If we had to start completely from scratch, we would have had to have spent five careers trying to do this."

Another advantage of having physician-scientists collaborate with basic scientists is that the former could understand and take advantage of the basic research and apply it to solve a clinical problem. Part of this was having the knowledge to construct the right paradigms and develop effective experimental models, he said. "It's these interactions with people of widely disparate backgrounds and experiences that produce the best results sometimes."

That's not to say it was easy.

McGowan said they had many failures until about three years ago when their persistence started to pay off. McGowan recalled finishing a case in the operating room and deciding it was time to test the latest shell version. They drew some of his blood and made it hypoxic, turning it dark red. When they injected the substance, his blood turned pink. It was a turning point. They then had a number of things to test, including defining the chemical and biologic characteristics of the microparticles' shells before designing an animal model to test the further refined foam suspension.

The suspension contains lipid-based microparticles, smaller than what would block the body's tiniest capillaries, that encapsulate a core of pure oxygen gas that can be delivered via intravenous injection. Once the shell delivers oxygen, it collapses to sub-micron size and is eliminated by normal body processes. The amount of lipid delivered is consistent with what can be tolerated in other medical applications, he said.

McGowan said the ability to administer oxygen and other gases directly to the bloodstream may represent a technique for short-term rescue of profoundly hypoxemic patients, to selectively augment oxygen delivery to at-risk patients or organs, or for novel diagnostic techniques. They will need further research to prove the lipid delivery system is safe and to find the optimum chemical formulation and delivery method.

One of the main advantages he foresees for clinical use is that it can buy time in situations with acute airway loss.

"We'd be able to buy five or 10 minutes with someone who could pull up with a cart and inject you with oxygen as we are preparing more definitive, longer-term therapy to restore your ability to oxygenate."

It will be five to 10 years before the research is ready for clinical applications, but a sampling of other possible uses that may prove successful are:

• a bridge to ECMO (extracorporeal membrane oxygenation) or endotracheal intubation;
• short-term treatment by paramedics and emergency room physicians for those with airway loss until they can be stabilized;
• delivering oxygen intravenously may allow reduced mechanical ventilation in patients with various kinds of lung disease, perhaps reducing ventilator-related lung injury;
• as a treatment for diabetic wounds (either topically or intravenously), which are notoriously hard to heal
• lower dosages for patients who only need partial oxygen replacement as might occur in situations such as lung injury or heart disease;
• for use in the battlefield for paramedics treating extreme blood loss or to improve the outcome of cardiopulmonary resuscitation (CPR).
  

"The toughest nut of all to crack and the one that is among the most interesting is the lower level, longer duration-needed application – the lung injury patient, or the cyanotic (blue) baby situation. Clinically, these may be some of the better applications, but experimentally, they're also some of the toughest models."

McGowan compares doing the research with his Boston and MUSC colleagues as similar to playing a team sport at a high level. It's constantly challenging and stimulating.

"I'm certain that I'm better clinically because of what we're doing in the lab, and I also think that I'm better in the lab because of what I do clinically. It really does inform in both directions."

Though he doesn't know what applications might pan out, McGowan said it's worth all the extra work. He apologizes for tearing up as he explains what motivates him to do translational research.

"Parents hand me their child every day to take into the operating room. I still don't know how they have the courage to do it. I usually have about 10 minutes to meet them and convince them to allow me to take care of their child. To continually try to be worthy of that trust and improve the outcome of what we do are the best parts of this."

Friday, Feb. 1, 2013