Tuesday, July 10, 2018

Dying Organs Restored to Life in Novel Experiments

Dying Organs Restored

When Georgia Bowen was born by emergency cesarean on May 18, she took a breath, threw her arms within the air, cried twice, and went into asystole.

The baby had had an attack, presumably while she was still within the womb. Her heart was profoundly damaged; an outsized portion of the muscle was dead, or nearly so, leading to the asystole.

Doctors kept her alive with a cumbersome machine that did the work of her heart and lungs.

The physicians moved her from Massachusetts General Hospital, where she was born, to Boston Children’s Hospital and decided to undertake a procedure that had never before been attempted during a person following an attack .

They would take a billion mitochondria — the energy factories found in every cell within the body — from a little plug of Georgia’s healthy muscle and infuse they into the injured the muscle of her heart.

Mitochondria are tiny organelles that fuel the operation of the cell, and that they are among the first parts of the cell to die when it's bereft of oxygen-rich blood. Once they're lost, the cell itself dies.

But a series of experiments have found that fresh mitochondria can revive flagging cells and enable them to quickly recover.

In animal studies at Boston Children’s Hospital et al. , mitochondrial transplants the revived cardiac muscle that was stunned from an attack but not yet dead, and revived injured lungs and kidneys.

Infusions of mitochondria also prolonged the time organs might be stored before they were used for transplants, and even ameliorated brain damage that occurred soon after a stroke.

In the only human tests, mitochondrial transplants appear to revive and restore the heart the muscle in infants that was injured in operations to repair congenital heart defects.

For Georgia, though, the transplant was an extended shot — the attack is different from a temporary loss of blood during an operation, and therefore the prognosis is stark.

there's only a short time between the onset of an attack and therefore the development of connective tissue was once there have been living muscle cells.

The problem was that nobody knew when the baby’s attack had occurred. Still, said Dr. Sitaram Emani, a pediatric cardiologist who administered the transplant, there was little risk to the infant and an opportunity, though slim, that some cells suffering from her heart attack might still be salvageable.

“They gave her a fighting chance,” said the infant’s mother, Kate Bowen, 36, of Duxbury, Mass.

The idea for mitochondrial transplants was born of serendipity, desperation and therefore the  lucky meeting of two researchers at two Harvard teaching hospitals — Dr. Emani at Boston Children’s and James McCully at Beth Israel Deaconess center.

Dr. Emani may be a pediatric surgeon. Dr. McCully may be a scientist who studies adult hearts.

Both were wrestling with an equivalent problem: the way to fix hearts that had been bereft of oxygen during surgery or an attack.

“If you narrow off oxygen for an extended time, the guts barely beats,” Dr. McCully said. The cells may survive, but they'll never fully recover.

While preparing to offer an interview to surgeons, Dr. McCully created electron micrographs of damaged cells.

the pictures clothed to be revelatory: The mitochondria within the damaged heart cells were abnormally small and translucent, rather than a healthy black.

The mitochondria were damaged — and zip Dr. McCully tried revived them.

One day, he decided simply to tug some mitochondria from healthy cells and inject them into the injured cells.

Working with pigs, he took a plug of abdominal the dimensions of a rubber eraser, whirled it during a blender to interrupt the cells apart, added some enzymes to dissolve cell proteins, and spun the combination during a centrifuge to isolate the mitochondria.

He recovered between 10 billion and 30 billion mitochondria, and injected one billion directly into the injured heart cells.

To his surprise, the mitochondria moved like magnets to the right places within the cells and commenced supplying energy. The pig hearts recovered.

Meanwhile, Dr. Emani was battling an equivalent heart injury in his work with babies.

Many of his patients are newborns who need surgery to repair life-threatening heart defects. Sometimes during or after such an operation, a small vessel gets kinked or blocked.

The heart still functions, but the cells that were bereft of oxygen beat slowly and feebly.

He can hook the baby up to a machine just like the one that kept Georgia Bowen alive, an extracorporeal membrane oxygenator, or ECMO.

But that's a stopgap measure which will work for less than a fortnight.

half the babies with arteria coronaria problems who find yourself  on an Ecmo machine die because their hearts cannot recover.

But at some point, Dr. Emani was told of Dr. McCully’s work, and therefore the two researchers met. “It was almost an ‘aha’ moment,” Dr. Emani said.

Dr. McCully moved to Boston Children’s, and he and Dr. Emani prepared to ascertain if a new technique might help tiny babies who were the sickest of the sick — those surviving on Ecmo.

It was shortly before that they had their first patient.

Early one Saturday morning in March 2015, the hospital got a call from a hospital in Maine.

Doctors there wanted to transfer to Boston Children’s a neonate boy whose heart had been bereft of oxygen during surgery to repair a birth defect.

The baby was on an Ecmo but his heart had not recovered.

“We turned the medical care unit into an OR,” Dr. Emani said.

He snipped a small piece of muscle from the baby’s abdomen. Dr. McCully grabbed it and
raced down the hall.

Twenty minutes later, he was back with a tube of valuable mitochondria. Dr. Email used an echocardiogram to work out where to inject them.

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