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Theoretically, anyone could do what Shelley Miyamoto, MD, pediatric cardiologist at Children's Hospital Colorado, does — study pediatric heart failure through muscle bath research — but it seems that almost no one else is doing it.
At least, that’s according to Dr. Miyamoto, who doesn't think her work is ingenious, but instead lauds the visionaries who had the foresight to build an infrastructure to study pediatric heart failure.
Pulling together the right team of experts
Part of that is what she calls the "serendipity" of having the right people in the right place at the right time. Those right people include Mike Bristow, MD, a cardiologist at University of Colorado Hospital, who first brought the muscle bath technology to Denver 40 years ago. Based at the Anschutz Medical Campus, he shares his equipment with other researchers in close proximity, including Dr. Miyamoto at Children's Colorado (which is also on the Anschutz Medical Campus).
Those right people also include Dunbar Ivy, MD, Chief of Pediatric Cardiology, whom she credits as having the vision to invest in several special freezers to store the tissue, allow her protected time to keep the tissue bank active, build a pediatric heart transplant program that would eventually amass enough hearts to create a significant tissue bank, and build an on-call team that could collect heart transplant tissue any time of the day or night, any day of the week.
"I've been fortunate because Dr. Ivy gets it," Dr. Miyamoto says.
The study that might lower mortality for children with heart disease
Hypoplastic left heart syndrome (HLHS), though quite rare, is the number one cause of heart-related death in infants. This severe form of heart disease requires sophisticated surgical, post-operative and outpatient care. Despite significant advancements in these areas over the past decade, many children still die prematurely.
"We can do both excellent clinical care and cutting-edge research because Dr. Ivy's leadership has made it happen." - Dr. Shelley Miyamoto
In an attempt to improve outcomes, Dr. Miyamoto is researching sildenafil, which is increasingly used to treat some kids with single ventricle heart disease.
According to the U.S. National Library of Medicine, sildenafil works in adults "by relaxing the blood vessels in the lungs to allow blood to flow easily." The drug is effective in helping children with HLHS who are not doing well because of inadequate blood flow to their lungs, but Dr. Miyamoto thinks there may be more to this story.
Working to improve outcomes for kids with HLHS
Dr. Miyamoto hypothesizes that sildenafil not only lowers the pressure in the lung blood vessels, allowing increased blood flow, but it also works directly on heart muscle cells to improve heart function. If this hypothesis proves true, sildenafil may be indicated in a wider range of children with HLHS and could improve outcomes for these children.
To find out, she's collaborating with the hospital's cardiac surgery team to collect heart tissue during the Norwood procedure, the first of three standard cardiac surgeries used to treat HLHS.
As a routine part of the procedure, the surgeon removes a tiny piece of heart tissue, which is otherwise discarded. Dr. Miyamoto recognized this as an opportunity to study the child’s heart without added risk, injury or inconvenience to the child or family. By simply adding a step in pre-op to obtain parental consent, Dr. Miyamoto can now study HLHS tissue (relatively) en masse. She has also created a process for gathering sick HLHS hearts after children receive a heart transplant.
Once Dr. Miyamoto collects the heart tissue, it is taken immediately to a lab at the University of Colorado where it is suspended in a muscle bath (a medication-infused solution) and electrically stimulated as a means of measuring muscle function. The tissue is exposed to various medications, including sildenafil, in different muscle baths. Dr. Miyamoto carefully measures the amount of contraction of the muscle.
Waiting to find out if sildenafil improves heart muscle function
Through these experiments, Dr. Miyamoto can observe if, in fact, sildenafil is improving the muscle’s function. If it is, then this would begin to form the evidence needed to prove that sildenafil could be a viable treatment of heart failure in children with HLHS.
"Kids deserve focused study," Dr. Miyamoto says. "We shouldn't just rely on what is known to occur in adults; you have to study children just as carefully, just as intensely, as you study adult disease."
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