http://www.newsweek.com/id/35045
To Treat the Dead
The new science of resuscitation is changing the way doctors think about
heart attacks—and death itself.
By Jerry Adler | Newsweek Web Exclusive
Consider someone who has just died of a heart attack. His organs are
intact, he hasn't lost blood. All that's happened is his heart has
stopped beating—the definition of "clinical death"—and his brain has
shut down to conserve oxygen. But what has actually died?
As recently as 1993, when Dr. Sherwin Nuland wrote the best seller "How
We Die," the conventional answer was that it was his cells that had
died. The patient couldn't be revived because the tissues of his brain
and heart had suffered irreversible damage from lack of oxygen. This
process was understood to begin after just four or five minutes. If the
patient doesn't receive cardiopulmonary resuscitation within that time,
and if his heart can't be restarted soon thereafter, he is unlikely to
recover. That dogma went unquestioned until researchers actually looked
at oxygen-starved heart cells under a microscope. What they saw amazed
them, according to Dr. Lance Becker, an authority on emergency medicine
at the University of Pennsylvania. "After one hour," he says, "we
couldn't see evidence the cells had died. We thought we'd done something
wrong." In fact, cells cut off from their blood supply died only hours
later.
But if the cells are still alive, why can't doctors revive someone who
has been dead for an hour? Because once the cells have been without
oxygen for more than five minutes, they die when their oxygen supply is
resumed. It was that "astounding" discovery, Becker says, that led him
to his post as the director of Penn's Center for Resuscitation Science,
a newly created research institute operating on one of medicine's newest
frontiers: treating the dead.
Biologists are still grappling with the implications of this new view of
cell death—not passive extinguishment, like a candle flickering out when
you cover it with a glass, but an active biochemical event triggered by
"reperfusion," the resumption of oxygen supply. The research takes them
deep into the machinery of the cell, to the tiny membrane-enclosed
structures known as mitochondria where cellular fuel is oxidized to
provide energy. Mitochondria control the process known as apoptosis, the
programmed death of abnormal cells that is the body's primary defense
against cancer. "It looks to us," says Becker, "as if the cellular
surveillance mechanism cannot tell the difference between a cancer cell
and a cell being reperfused with oxygen. Something throws the switch
that makes the cell die."
With this realization came another: that standard emergency-room
procedure has it exactly backward. When someone collapses on the street
of cardiac arrest, if he's lucky he will receive immediate CPR,
maintaining circulation until he can be revived in the hospital. But the
rest will have gone 10 or 15 minutes or more without a heartbeat by the
time they reach the emergency department. And then what happens? "We
give them oxygen," Becker says. "We jolt the heart with the paddles, we
pump in epinephrine to force it to beat, so it's taking up more oxygen."
Blood-starved heart muscle is suddenly flooded with oxygen, precisely
the situation that leads to cell death. Instead, Becker says, we should
aim to reduce oxygen uptake, slow metabolism and adjust the blood
chemistry for gradual and safe reperfusion.
Researchers are still working out how best to do this. A study at four
hospitals, published last year by the University of California, showed a
remarkable rate of success in treating sudden cardiac arrest with an
approach that involved, among other things, a "cardioplegic" blood
infusion to keep the heart in a state of suspended animation. Patients
were put on a heart-lung bypass machine to maintain circulation to the
brain until the heart could be safely restarted. The study involved just
34 patients, but 80 percent of them were discharged from the hospital
alive. In one study of traditional methods, the figure was about 15 percent.
Becker also endorses hypothermia—lowering body temperature from 37 to 33
degrees Celsius—which appears to slow the chemical reactions touched off
by reperfusion. He has developed an injectable slurry of salt and ice to
cool the blood quickly that he hopes to make part of the standard
emergency-response kit. "In an emergency department, you work like mad
for half an hour on someone whose heart stopped, and finally someone
says, 'I don't think we're going to get this guy back,' and then you
just stop," Becker says. The body on the cart is dead, but its trillions
of cells are all still alive. Becker wants to resolve that paradox in
favor of life.
© 2007 Newsweek, Inc.
