If your heart stops beating, standard medical procedure is to shock it back into action with a defibrillator. This has to be done fast, so that your blood will resume supplying oxygen and glucose to the brain. But if you experience cardiac arrest when you're not in a hospital, paramedics are unlikely to reach you soon enough to avert permanent damage.
Unexpectedly, a technique that fills the lungs with a chilled, breathable liquid may revolutionize this dismal picture. Researchers claim that the liquid treatment can double the survival times without blood flow and enable perhaps one patient in three to survive cardiac arrest. The national average is around one in 20.
The key discovery was made by Peter Safar, a doctor best known for introducing the techniques of cardiopulmonary resuscitation to the United States almost 50 years ago. Now in his seventies, Safar is still the best-known figure in resuscitation medicine and continues to do research at his lab at the University of Pittsburgh Medical Center. The fundamental challenge of resuscitation, he says, lies not in the heart but in the brain: "When sudden cardiac death occurs at normal body temperature, brain damage will be permanent after five minutes."
Although the heart can recover after nearly 20 minutes without a beat, brain cells are more delicate. When blood stops flowing, the cells exhaust their oxygen reserves in a mere 10 seconds, at which point the patient loses consciousness. After the last reserves of glucose disappear five minutes later, cells literally poison themselves with a toxic cascade of chemical reactions.
In the 1980s Safar happened to discover that this toxic cascade can be slowed by "mild hypothermia"— lowering the body temperature by just 7.2 degrees Fahrenheit. In experiments on dogs, he found that if he lowered their temperature for 12 hours while increasing blood pressure just enough to keep blood moving through stressed blood vessels, the five-minute time limit for surviving cardiac arrest could be extended to 10 minutes. But Safar's procedure was never implemented because no one could find a simple way to cool a human fast enough. The technique Safar had used in his animal experiments— rerouting and cooling blood through a miniature heart and lung machine— was far too surgically complex for paramedics to use in the field.
Then researcher Michael Darwin got wind of a different approach. In 1997 Darwin was director of research at 21st Century Medicine (now called Critical Care Research), a small laboratory in southern California privately funded by the Life Extension Foundation, a vitamin mail-order business. He had read about a bizarre experiment that showed a mouse could survive while immersed in a liquid known as perfluorocarbon. The perfluorocarbon family of chemicals, made of mostly fluorine and carbon, are so chemically inert that they don't harm the delicate, air-filled pockets in the lungs. And perfluorocarbons can be loaded with metabolically useful gases such as oxygen or carbon dioxide.
These two prototypes for rapidly cooling the brain are still too large for use in the field. The goal is a device that can fit inside two suitcases.Photograph courtesy of Scott Nelson/Critical Care Research
Darwin imagined how such a treatment could be used to save patients in cardiac arrest. When paramedics arrived at the scene, they would first restart the patient's heart with a standard defibrillator. Then they would deliver perfluorocarbon into the patient's lungs via an endotracheal tube (a standard device normally used to force oxygen into the lungs of an unconscious patient). The perfluorocarbon could serve a dual purpose. It would carry enough oxygen to sustain life, and if it were chilled, it would cool the blood via the vast network of capillaries in the lungs. The blood would then circulate and cool the brain.
Unfortunately, Darwin found that a group of researchers had beaten him to it. But they had failed to make a device that cooled effectively. So he decided to run his own experiments in collaboration with Steven Harris, a doctor at Critical Care Research who had worked previously at the University of California at Los Angeles on longevity research. They experimented on anesthetized dogs, using an endotracheal tube as Darwin had imagined it. But they altered the concept by using a tube within a tube to supply oxygen and perfluorocarbon simultaneously and separately: The outer tube carried oxygen; the tube within carried perfluorocarbon. This innovation not only simplified the equipment but also produced more efficient cooling.
"We got a cooling rate three times as high as anyone else had achieved with external cooling," Harris recalls, "probably because the gas causes turbulence," which distributes the cooling liquid very effectively throughout the lungs. In 18 minutes, blood temperature fell by 14 degrees Fahrenheit, causing brain temperature to fall by 13.3 degrees. All the animals recovered fully, except for one that succumbed to an infection unrelated to the experiment.
Harris, Darwin, and their small research team made a preliminary announcement at a medical conference in 1999. The discovery created a sensation, and rapid brain cooling soon attracted attention from other, better-funded institutions. Lance Becker is director of the emergency resuscitation center at the University of Chicago. Becker discovered that Ken Kasza, an engineer at the nearby Argonne National Laboratory, had spent 12 years perfecting tiny ice particles so round and smooth they form a "slurry" like a milk shake when they're mixed with water. Kasza had developed his ice slurry for cooling office buildings, but Becker saw that it could be used for cooling humans.
Although Becker and Kasza are reluctant to comment on the work by Darwin and Harris, their research in Chicago started shortly after the 1999 presentation by the California scientists. A year later, Becker and Kasza tested a perfluorocarbon containing 35 to 40 percent ice on three pigs that had been killed immediately before the experiment. The technique achieved cooling rates comparable to those at Critical Care Research. The American Medical Association featured the work prominently in a recent press conference.
Harris was surprised when he saw the attention his competitors received. "We've already cooled 12 living dogs and rewarmed all of them successfully," he says. And he has already tested a device to deliver perfluorocarbon in the field. Prechilled modules can be loaded onto an ambulance responding to an emergency call. Perfluorocarbon liquid will then flow through an array of modules, down a tube in the patient's throat, and into his lungs. The system is automated so that perfluorocarbon is sucked out and pumped in about every 30 seconds. A sensor keeps track of the blood temperature in the eardrum. Once the patient is stabilized in the hospital, reduced body temperature can be maintained by more traditional methods, such as ice packs or cooling blankets. Five prototypes are being built, one of which will go to Peter Safar.
"Dr. Harris sounds very credible," says Safar, "and we will be happy to test his device." Safar views the sudden interest in body cooling with wry detachment. "Many people have jumped on the bandwagon of hypothermia," he notes, adding that another small company, Accuspix, has begun to research strategies for rapid cooling.
"In retrospect," says Harris, "it seems quite obvious that damage to the brain following cardiac arrest is largely a chemical and inflammatory process, which can be reduced by cooling, just as you would cool a sprained ankle."Obvious or not, if a cooling device can be made to work successfully on people, researchers estimate it could save 100,000 lives a year.
For a technically detailed introduction to the concept and application of liquid ventilation, visit the University of Michigan's Web site at www.med.umich.edu/ liquid/whatislv.html.
