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
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.