“It is well known that human beings cannot exist without a functioning heart for much more than three minutes,” he says in an early article. This, he continues with typical Canadian understatement, makes heart surgery “a challenge to the surgeon.”
No kidding. Imagine stopping the heart, fixing a heart valve or grafting an artery, as Allan’s surgeons did, and then putting everything back together again, in three minutes. It’s just not possible.
The solution, which apparently came to Bigelow in his sleep one night, was inspired by his experiences in World War II. “I was interested in cooling limbs to see if you could protect them,” he explained in an interview. But one night his subconscious took over and he developed far grander plans. “One day I woke up and thought, Why not cool the whole body.”
Bigelow was the first to note that dogs could survive fifteen minutes of circulatory arrest if they were chilled to lower than 25 degrees Celsius. In one experiment, thirty-nine “mongrel dogs of medium size” were given an anesthetic and drugs to stop their hearts, then they were chilled to 20 degrees Celsius using a cooling blanket. Next, Bigelow opened the dogs’ chests and closed off the vessels leading into the heart with “bull dog clamps,” a name whose irony these dogs were probably in no condition to appreciate.
After fifteen minutes, the clamps were released, the dogs were rewarmed, and efforts were made to bring them back. Nineteen of the thirty-nine died. This is a success rate that Bigelow admitted later, in a rare moment of candor, was “disappointing.” I’m sure it’s particularly disappointing if you happen to be a mongrel dog of medium size.
Then Bigelow had another epiphany. Maybe, he thought, dogs weren’t the best test subjects?
He turned his attention to two other species: rhesus monkeys and groundhogs. Monkeys were “more akin to man,” and groundhogs, which hibernate during the winter, might withstand even lower temperatures.
Bigelow’s experiments with rhesus monkeys followed essentially the same technique that he’d used for the dogs, with a few variations. For instance, after the monkey’s chest was opened and the right-side vessels were clamped, the heart was opened as a “token operation.” Monkeys went without circulation even longer than the dogs had (up to twenty-four minutes) and at a lower temperature (between 16 and 19 degrees Celsius). At the end, the monkeys were sewn up, rewarmed, and revived.
Of twelve monkeys that underwent a total of thirteen procedures, eleven lived. Bigelow observes, “They were all quite active and well coordinated the day after exposure, and the procedure did not appear to alter their personality or responses in any way.”
Of the eleven survivors, most either died of infection as a result of the procedure or were volunteered for further experiments. But one was “saved.” Approximately eighteen months after his experiment, Bigelow reported, he was alive and well, and serving as the mascot of a naval station. “He appears normal in all respects,” the paper concludes. Except, of course, for the fact that he was a naval monkey mascot. But maybe in Canada that’s entirely normal.
Next up were six groundhogs.
Perhaps sensing the lack of potential for narrative drama when discussing groundhogs, Bigelow gets right to the point. First, fully conscious groundhogs were hoisted by their tails and their bellies were injected with sodium pentothal as an anesthetic. Then they were treated just like the monkeys, except that the groundhogs were cooled to between 2.5 and 5 degrees Celsius while their circulation was interrupted for up to two hours.
How did the groundhogs do? Of the six that began the experiment, one died due to hemorrhage, but the remaining five “appeared as well co-ordinated as they were preoperatively.” You’ll need to decide for yourself just how coordinated an upside-down groundhog might be when it’s suspended by its tail and is poked in the belly with a large needle. I’m thinking that the baseline is probably not so good. None of the groundhogs, as near as I can tell, became a mascot of anything.
To be fair, Bigelow acknowledges the risks of hypothermia, an admission that will probably cause the ghosts of an entire menagerie of rhesus monkeys, groundhogs, and mongrel dogs of medium size to nod vigorously in unison. But, ever the cheerful Canadian, he concludes: “We feel, however, that cooling dogs to 20 C with re-warming is a safe procedure.” Unless, of course, you happen to be a mongrel dog of medium size, a rhesus monkey, or a groundhog, in which case it’s probably safer to stay home.
It turns out that Bigelow was right, and that cold is the secret to survival. Indeed, if anything can rewrite the mitochondria tragedy, it’s cold. If cold could protect dogs and groundhogs and monkeys, Bigelow thought, maybe it could protect people, too. Think about Anna Bågenholm’s amazing recovery after being pulled from an icy river. But it wasn’t until more than fifty years after Bigelow’s experiments that the science had evolved sufficiently to prepare the next scene. And that scene played out—where else?—in the original city of zombies.
ZOMBIE DOGS
Early in Night of the Living Dead, Johnny and his sister, Barbra, arrive at a spooky graveyard near Pittsburgh to pay their yearly respects to their deceased father. Little did they realize it was the day of the Great Zombie Uprising. Barbra is creeped out by the graveyard and Johnny is making the best of the situation by teasing his sister mercilessly.
“They’re coming to get you, Barbra,” he says devilishly. There is nervous laughter. Then things get ugly.
Zombies are not real, and Pittsburgh, I’m happy to report, is a very pleasant city. It’s full of nice, normal people and entirely devoid of the walking dead. But there was a time not long ago when there really was a kind of zombie there.
Those zombies weren’t people, though. They were dogs. Zombie dogs.
At least, that’s the unfortunate nickname that a couple of enterprising journalists gave to some very serious and innovative research that was conducted at the Safar Center for Resuscitation Research at the University of Pittsburgh. (The center is named after its founder, Dr. Peter Safar, whom we’ll meet in chapter 6.) In these amazing experiments, conducted in the early 2000s, dogs were dead for up to three hours. Then, miraculously, researchers brought them back to life.
Those experiments drew a flood of media attention, which is usually a good thing. In fact, it’s at least in part thanks to the media coverage of the Safar Center’s previous groundbreaking experiments that the institution is known as the birthplace of CPR.
However, as the researchers at the Safar Center discovered, you really, really don’t want to become known as the place that created zombie dogs. And that phrase, certain to be offensive to dog lovers, other scientists, and probably George A. Romero, is the one to which the center’s name is inextricably tied. Forever.
Regardless, I’d really like to learn something about these experiments. But I discover almost immediately that if you want to talk to serious researchers about a serious topic like resuscitation, it’s not wise to begin a conversation by inquiring about their institution’s previous experience with creating zombie dogs. This becomes readily apparent in a telephone conversation with Anita Srikameswaran, the media relations contact for the Safar Center.
“We don’t do those experiments anymore,” she says with a little more emphasis than is absolutely necessary.
“No dogs,” she adds severely, just in case she hadn’t been clear.
Then: “None of those experiments.”
And that’s too bad, in a way, because those experiments offered a rare glimpse of what the future of resuscitation might look like. In the mid-2000s, the Safar Center’s team was pursuing a line of research into the applied science of hypothermia that they hoped might eventually help patients. Specifically, they focused on patients with severe trauma and the sort of massive blood loss that might result from a motor vehicle accident, gunshot wound, or injuries suffered on the battlefield, the latter of which were on the rise.
The Safar Center did several experime
nts along these lines, which were published in respected medical journals. (None of those articles, by the way, said anything about “zombie dogs.”) Together, those experiments searched for ways to improve the chances of successful resuscitation through a variety of interventions that include drugs, devices, and temperature regulation.
What did they do? Well, first I should mention that if you’re a dog lover, you might want to skip ahead to the next section.
In one experiment, “custom-bred, male hunting dogs” were anesthetized and intubated, and catheters were placed in a vein and in an artery. Then the dogs were taken off the ventilator and blood was removed through a catheter until the dog’s blood pressure was 20 mm Hg (normal is more than 100 mm Hg). Finally, the dog’s heart was shocked, causing fibrillation. This was done to ensure “zero blood flow,” as the article puts it.
Then the researchers packed the dogs in ice and connected them to a cardiopulmonary bypass machine that circulated cold saline solution through the circulatory system instead of blood. In addition, some dogs received oxygen or glucose, or both. The dogs were sustained like this, on bypass but with no ventilation or any other measures, for up to three hours.
This is the point at which things start to get interesting. This is also the point at which any remaining dog lovers should heed that advice about skipping ahead. Seriously.
After spending up to three hours with nothing but chilled saltwater instead of blood, the dogs were rewarmed, and their hearts were restarted. They were also given back the blood that had been stored for them. Thoughtful, I guess.
Then the researchers watched the dogs closely, checking on them every six hours. At the end of the experiment, seventy-two hours later, the dogs that had received oxygen and glucose did the best, and the dogs who didn’t receive either did the worst. Of the twenty-four dogs in the experiment, only four were neurologically normal, which is disappointing. But in the glucose/oxygen group, all regained consciousness. Even better, two were normal and the other four had only moderate disability at seventy-two hours. (Although there is no mention in the article of what happened after seventy-two hours, the subsequent description of what the dogs’ brains looked like under a microscope should lead savvy readers to recognize that the dogs were eventually euthanized. So we don’t know what they would have been like weeks or months later.)
Those experiments led to a storm of media attention, which was both useful and regrettable. Useful because it ignited interest in what was a quantum leap in the science of resuscitation. The ability to revive a dog after three hours without a heartbeat opened the door to a new world of clinical care. If these techniques could be extended to people, accident victims could be stabilized in the field before transport, for instance. And casualties on the battlefield could be airlifted to a well-equipped surgical suite hundreds or even thousands of miles away. All of that was exciting, promising, and awe-inspiring. Or, at least, it should have been.
But a media frenzy was perhaps inevitable, particularly given the rather unfortunate coincidence that the city of Pittsburgh had given birth to cinematic zombies approximately forty years earlier. News reports, for instance, ran with goofy headlines like: “Night of the Living Dogs.” The Safar scientists found themselves tossed into the sordid world of tabloid science coverage in which dogs are “hapless pooches” and carefully designed experiments are “unsettling tests.”
As if that wasn’t bad enough, one article reported that the center’s director, Dr. Patrick Kochanek, “angrily denies he’s creating a race of zombie dogs fit for a Stephen King novel.” That, it seems to me, was sort of a journalistic low blow. It’s a little like reporting that Kochanek angrily denies beating his wife. Something any non-wife-beating person would angrily deny.
Predictably, People for the Ethical Treatment of Animals (PETA) weighed in too. Their spokeswoman, Mary Beth Sweetland, declared: “These experiments are indefensible nonsense and the results for humans will be negligible. I would also imagine there are serious consequences for these animals that aren’t discussed.”
Regardless of what you might think about this particular use of male hunting dogs, Sweetland’s dismissal of this line of research as “indefensible” is unfair. And untrue. In fact, these experiments offered pretty convincing evidence that the science of hypothermia could be used to help people. And now it seems pretty likely that Anna Bågenholm survived at least in part because she spent a good portion of her pulseless time submerged in ice-cold water. Whatever your emotional reaction to these experiments, the data were promising and took us a few steps closer to a science that can make miracles like Bågenholm’s commonplace.
However, dogs aren’t people, and it’s a long way from these advances in controlled laboratory settings to eventually helping an accident victim. It’s one thing to discover that cold is protective, but quite another to figure out how to cool a gunshot victim on a street corner, or a wounded soldier on the battlefield. To find out how that might work, I have an appointment with someone who thinks an awful lot about cooling people, and pigs.
A PIG NAMED PETUNIA: THE ART AND SCIENCE OF CHILLING
Petunia, I regret to report, is not doing well. I know this because Petunia doesn’t have a pulse. Nor is she breathing. In fact, I think it’s safe to say that Petunia is no longer alive.
Petunia is what I’ve nicknamed this example of a Sus domesticus. That is, she’s a pig. More specifically, she’s a pig who is about to teach me something about how it might be possible to cool someone quickly and safely, perhaps saving them in the same way that immersion in an ice-cold stream saved Anna Bågenholm.
To find out how this might work, I’m visiting Petunia and her caretaker, Josh Lampe, a bearded, preternaturally mellow guy who favors soft flannel shirts and worn khakis. He’s a bit of an anomaly in the CPR world, because he’s not a physician or a biologist, but an engineer. It turns out, though, that if you want to find out how to cool someone, an engineer is exactly who you want on your side.
It’s about ten years after the Safar Center experiments and we’re in his lab, which is a windowless, low-ceilinged room with bare walls and pristine tile floors. In addition to Josh and me, there are two other people who are wearing gowns and masks and cute hairnets just like I am. One waves a gloved hand. The other nods. This is not a particularly talkative group, it seems, when they’re in the middle of an experiment.
I can hardly blame them, though. We’re surrounded by racks and racks of computer equipment, whose steady stream of flashing lights and beeps seems to require all of their attention. I also count no fewer than three open laptops that are busily harvesting every piece of data that Petunia is giving us. Imagine the lights and dials and knobs in a 747’s cockpit, churned up in a blender and scattered around an average-size hotel room and you’ll have a pretty good idea of the sensory overload these guys have to manage.
Petunia is at the center of all of this, lying on her back on a wheeled cart. She’s connected to an intricate web of wires and tubes that are monitoring her temperature, oxygen status, and, even at a microscopic level, her mitochondrial function. The crowning element of this setup is an extruded aluminum arch that is placed over Petunia. A motor at the top is driving a three-by-three-inch “fist” that connects with her chest at a rate of about a hundred times per minute. Josh explains that this fist is an automated version of a rescuer performing chest compressions. Unlike a real rescuer, though, this fist doesn’t get tired, and it never misses a beat. It will keep going until Josh turns it off. But that won’t happen for another hour. In the meantime, Josh and his group are trying to learn as much as they can from Petunia about how to cool a pig and, ultimately, a person.
As Josh is explaining the tubes and wires that monitor Petunia, he emphasizes that he and other animal researchers are monitored almost as closely by various review boards. There are scientific review boards and ethical animal use review committees. This isn’t, Josh emphasizes, some W
ild West of experimentation, and researchers don’t have a cavalier attitude toward the animals they use.
As if in agreement, with each chest compression, Petunia’s right forefoot wiggles, just a little. Up-down-up-down. I can’t help thinking that Petunia is waving at me.
Now I’m looking back and forth between Josh and Petunia, musing on the wide gap between them. Josh’s research is ultimately about saving people, but we’re looking at a pig. Why pigs?
When I put this question to Josh, he shrugs in a way that suggests he’s heard this question a few thousand times before. “Pigs and people are different,” he admits. “But they’re actually more similar than you might think.” He launches into a technical description of heart muscle and valves that loses me quickly. The point, though, is that despite their differences from humans, pigs are similar enough to make them the best test subjects for studying the way that CPR works.
Josh notes that the biggest challenge isn’t anatomy, it’s pathology. Or lack thereof. “One big problem is their state of health. Animal models of CPR generally have normal hearts. But most people who have a cardiac arrest are going to have heart disease and clogged arteries. So that’s a big difference right there.
“And,” he adds, somewhat unnecessarily, “there are anatomical differences in the way they’re shaped.” He pauses. “Human chests are flat, whereas pigs”—he points at Petunia—“and most dogs, have ‘keel chests [chests that protrude].’ So it can be difficult to simulate CPR as it’s done in humans.”
I think for a moment about the dogs I’ve known. I open my mouth, but Josh is already nodding, as if this is something he’s given a lot of thought to. I begin to suggest that there are breeds that have broader, flatter chests, like—
“Dachshunds.”
I try to imagine for a moment the reaction of the Dachshund Club of America to the news that their breed has an anatomy that is uniquely favorable for resuscitation experiments. I’m guessing that they would not be overjoyed by that news.
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