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Last updated on April 17, 2014 at 8:37 EDT

Artificial Blood Going From Science Fiction to Science Fact

March 18, 2008

At 20, Bess-Lyn Sannino was a self-described punk rocker with spiky black hair and seven tats from her neck to her left hand. She liked to play rock music on her cello and tended to ride her bike without a helmet. But she was no match for the concrete wall she hit when she lost her brakes going down a steep hill.

At 22 now, feisty as ever, she’s a poster child for a new type of artificial blood that helped her come back from traumatic brain injury.

“It works,” she says. “I’m totally for it.”

And she’s a powerful inspiration for a 200-patient human trial about to start at the University of Miami School of Medicine into Oxycyte, a Teflon-like liquid that carries four times the oxygen levels of real, red blood cells to brain tissue damaged by traumatic injury. Without that continuous flow of oxygen, brain cells can die within hours.

If it succeeds in civilian trials here, it could be on the battlefield in Iraq in a year or two to help soldiers who suffer traumatic brain injury from IEDs — improvised explosive devices. TBI has been called “the signature wound” of the Iraq war, with 1,882 cases treated to date. The Department of Defense has signaled its interest in Oxycyte by funding $1.9 million of the $4 million cost of the trials.

“If we can interrupt the cascade of cell death during the hours and days after the initial brain injury, we can save someone from a lifetime of disability,” says Dr. M. Ross Bullock, director of clinical neurotrauma at the University of Miami School of Medicine. He’s the lead investigator on the trial, which will take place over the next year at the Miami Project to Cure Paralysis. At the same time, other researchers at the Miami Project will be studying Oxycyte for use in spinal cord injury, says Dr. W. Dalton Dietrich, the project’s scientific director.

“If we can improve oxygen flow to the compromised area of the spinal cord, and start early enough, some patients can probably benefit,” he says.

Other doctors are researching whether Oxycyte can help with stroke, heart attack, cancer, sickle cell anemia, even hard-to-heal diabetic wounds and bed sores. They acknowledge it sounds too good to be true.

“If this works, it will be very big,” says Dr. Harvey Klein, chief of the Department of Transfusion Medicine at the National Institutes of Health, who is not involved in the UM trials. “But my enthusiasm is tempered by 20 years of experience with these drugs where they haven’t worked.

“The proof of the pudding will be in the clinical trials.”

Dietrich expresses hope: “We do so many complicated things trying to heal injuries. But the simplest way is to improve the flow of blood and oxygen. At the end of the day, if tissue is starved of oxygen, it dies.”

The trials, starting in June, will involve 200 patients in hospitals in the United States, including UM, Virginia Commonwealth University, the University of Pennsylvania, Fairfax Hospital in Virginia and possibly hospitals in Toronto, Heidelberg, Germany and Bern, Switzerland.

Two-thirds of the patients, victims of severe brain injury from car accidents, household falls, gunshots and other causes, will be treated with Oxycyte, the rest with inert placebos. Electronic monitors implanted in their brains will gauge the effects.

“We’re looking for safety and efficacy — whether it works,” Bullock says.

Every year, 1.1 million Americans suffer brain injuries, with 70,000 characterized as severe. About 50,000 of them die before reaching the hospital, and 40 percent of the rest die in the hospital over the next few days, Bullock says.

“The biggest reason is that the brain can’t get enough oxygen,” he says.

When a traumatic injury occurs, tiny blood vessels called capillaries are torn and swollen, and oxygen-carrying red blood cells can’t get through. Oxycyte can carry four times as much oxygen as red blood cells, and the particles in it are much smaller (0.2 microns across compared with 7.0 microns for red blood cells) — making Oxycyte a more agile transport vessel.

Also, since it’s based on a chemistry similar to that of Teflon, it’s slipperier than blood, which means it’s better able to push through swollen capillaries.

Bullock says tests he supervised at Virginia Commonwealth University in Richmond, both animal trials and a small trial of nine brain-injured human patients, including Sannino, were encouraging.

Two of the nine human patients died, he says, but researchers had selected the “worst of the worst” in terms of injury and would have expected 60 percent of them to die.

“The rest made good, functional recovery and are back at work or in college,” Bullock says.

Attempts to replace human blood go back hundreds of years to when physicians experimented disastrously with everything from dog’s blood to milk to urine. Today’s Oxycyte is based on chemical experiments with perfluorocarbons (PFCs) going back to the 1930s.

PFCs were developed as part of the Manhattan Project and the development of an atomic bomb during World War II; they can carry away enormous amounts of heat from atomic reactions.

PFCs are clear, odorless, nonconducting, nonflammable silicone oils with a chemical structure similar to that of Teflon. They have twice the density of water, capable of absorbing and carrying large amounts of oxygen. They are not metabolized in the human body.

To be used as artificial blood, PFCs must be emulsified with water, salt and egg yolks by steam pressure, turning milky white in the process. They become PFCEs — perfluorocarbon emulsions. Today’s Oxycyte is a third-generation successor to perfluorocarbon emulsions (PFCEs) developed in the late 1980s and early 1990s, Bullock says.

In experiments in the ’90s, PFCEs were used to replace all of the functions of real blood — carrying not just oxygen, but also carrying nutrition, hormones and so on. The experiments didn’t work well, and some patients died from stroke.

Bullock, 56, was born in Zimbabwe and studied medicine in the United Kingdom and South Africa, and came to VCU’s division of neurosurgery in 1992. He began working with Dr. Bruce D. Spiess, professor of anesthesiology and emergency medicine at VCU, who was analyzing PFCEs in the form of Oxycyte. Synthetic Blood International of Costa Mesa, Calif., developed Oxycyte.

Bullock joined UM last year; he’s focusing on the oxygen-carrying abilities of PFCEs.

Says Spiess: “This isn’t new. I’ve worked on the precursors to it for 26 years. Previous generations of PFCEs were misunderstood. People tried to use them as an entire blood substitute. That’s barking up the wrong tree.”

He’s enthusiastic about Oxycyte’s chance of success. “It’s very, very, very likely. I’d say 90 percent.”

Still, there are dangers.

“There’s an awful lot of proving to be done,” says Bullock. “And Oxycyte is a pretty foreign substance to be putting in the body.”

In the animal trials, Oxycyte caused liver swelling in rabbits but not in rats. The humans in the small trial had few side effects, he said. “You can’t always predict a drug’s safety or efficacy,” says Klein. “Sometimes it’s safe in normal volunteers, but when you use it in patients with problems, you can have a problem.”

Susan H. Connors, president of the Brain Injury Association of America, says proving new therapies like Oxycyte is very important.

“Traumatic Brain Injury is one of the largest injuries from the war. But there are also so many civilian injuries from falls, motor accidents and other causes. Things as simple as falling off a ladder.”

Back in East Hampton, Mass., Bess-Lyn Sannino, long out of her coma, the use of her right arm restored, is riding her bicycle again — no longer forgetting her helmet. She has no memory of her week-long coma, or when doctors cut away a piece of her skull to relieve swelling, or the Oxycyte she was given intravenously.

The Oxycyte carried oxygen to areas in her brain where her red blood cells, being much bigger, couldn’t get through, and prevented the cascade of brain cell death that could have killed her or left her paralyzed, says Bullock.

“I feel pretty much fully recovered now,” she says.

She’s studying creative writing at Holyoke Community College and training in cosmetology to pay expenses.

“I’m trying to make something of the rest of my life. I don’t want to live on Social Security disability forever,” she says.

Her mother, Grace LeClair, of Virginia Beach, Va., is proud.

“She’s a darling girl with a heart of gold, and a punk rocker on the side. It’s that feistiness that got her through this.”

Two years ago, LeClair had just learned of her daughter’s accident and was driving to Richmond, Va., to be with her when she got the call from Bullock asking if he could put her in his first small Oxycyte trial. Based on that conversation on her cellphone, she gave her consent.

“He said it was to increase oxygen,” she says. “It sounded like a good idea.”