Jalife also discovered that a spiral wave does not have to remain at a fixed position. When the spiral moves, it can start to meander, like a top slowing down on a table, its tip tracing a curlicue pattern. Eventually, the spiral wave can pick up so many oscillations that it breaks up, creating multiple independent spirals that stimulate the heart in a disordered fashion, as when waves collide at the shore, leaving thick, turbulent foam. This is ventricular fibrillation, an arrhythmia so fervent, so committed, so devoted to its mission that you literally have to shock it out of the heart to make it stop. The Scottish physiologist MacWilliam wrote of ventricular fibrillation in 1897, “The ventricular muscle is thrown into a state of irregular contraction, whilst there is a great fall in the arterial blood pressure. The ventricles become dilated with blood as the rapid quivering movement of their walls is insufficient to expel their contents.” This is essentially electrical chaos, and the heart (and its owner) quickly die.2
In a 2000 study in the Proceedings of the National Academy of Sciences, Alan Garfinkel and his colleagues at UCLA imaged slices of pig hearts using a special microscope to show that when the tissue fibrillated, spiral waves were breaking up into multiple new waves that activated the heart in a chaotic pattern. It is not known precisely why spiral waves break up, resulting in fibrillation, but it is believed to depend on how quickly heart cells recover their ability to be re-excited, a property known as restitution. Restitution depends on many factors, but it can be amplified by lack of coronary blood flow—the mechanism that killed both my grandfathers—as well as by surges of adrenaline during psychological stress. Whatever the reason, when heart cells become more excitable, a spiral wave can become exquisitely sensitive to small perturbations in the electrical environment, picking up oscillations and setting up the conditions for breakup. “Steepening” of cardiac restitution may even be the mechanism behind “voodoo death,” the mysterious, sudden demise documented by anthropologists that often occurs during periods of intense emotional stress, such as after a witch doctor’s curse. Beta-blocking drugs that antagonize adrenaline have proved effective in preventing such fatal arrhythmias, which is perhaps why Mitch Shapiro, the Bellevue electrophysiologist, often said that beta-blockers should be put into New York City’s water supply.
* * *
Mines’s research on reentry and the vulnerable period inspired a new era in cardiac electrophysiology. Unfortunately, he did not live long enough to see the impact of his work. On the chilly Saturday evening of November 7, 1914, a janitor entered Mines’s laboratory at McGill to find him lying unconscious under a lab bench with monitoring equipment attached to his body. He was rushed to the hospital but died shortly before midnight without recovering consciousness. Though an autopsy was inconclusive, medical historians believe his death was the result of experimentation on the vulnerable period in a human: himself. This speculation was fueled by a lecture that Mines delivered to McGill faculty one month before his death, when he was twenty-eight. In the talk, Mines spoke in praise of self-experimentation, referring to the work of contemporaries who severed their own nerves to understand the nature of skin sensations or swallowed a plastic tube to study the physiology of digestion. Evidently, Mines decided to put his theory of the vulnerable period to the test on himself. Mines did not know about Werner Forssmann. His tragic self-experiment predated the great German’s self-catheterization by fifteen years.
10
Generator
When a condition is recognized as offering only a fatal or hopeless outlook, desperate measures seem less desperate and with application and courage not infrequently can be made safe.
—Charles P. Bailey, cardiac surgeon, Hahnemann Medical College, Philadelphia
“I told him that if he doesn’t do something, he’s going to be dead by the end of the year,” Shawn, my magnet-wearing patient Jack’s visiting nurse, told me on the phone one afternoon. “His heart is going to conk out, and he doesn’t have time to play with these so-called nutraceuticals.” Shawn paused, obviously frustrated. “You know what he said to me?” Shawn spit out the words in disgust. “‘Will it be painless?’”
I’d been calling Jack, my clinic patient, about once a week to check on him, but despite worsening heart failure he’d been resistant to my recommendations, convinced that his herbals and magnets would eventually work. Because of a lack of family and social support, Jack wasn’t eligible for a heart transplant. There was no one available to assist him with chores or ensure he’d make it to his appointments or take his medicine. His only options were a $40,000 surgically implanted defibrillator—or hospice. I didn’t hear anything for a few days. Then Shawn called to tell me that Jack was feeling sick again. He was sleeping sitting up in a chair because of the fluid accumulating in his lungs and was waking up every couple of hours gasping for air. Shawn had finally persuaded him to get the device.
I admitted Jack to the CCU at Bellevue and scheduled a cardiac catheterization prior to the implant. True to form, he quickly became annoyed with the hospital staff. One morning I was urgently paged to the unit because Jack was fighting with the nurses to go home. When I arrived, he was in a small, curtained space, lying on crumpled sheets in a fetal position. Thin plastic tubing delivering supplemental oxygen was pressed tightly against his sunken cheeks. I immediately turned the green knob controlling the flow of oxygen. A tiny ball bearing shot up in a plastic meter, suspended by the increased flow of air.
“I’m having pain in the middle of my chest,” Jack said, without looking at me. A stained white knit cap had replaced his bowler. He looked even more emaciated than when I’d seen him in the clinic. I felt pity, but a bit angry, too. “This is why you need an angiogram, Jack,” I said.
“You should have done it this morning,” he growled, his eyes flashing anger even as they tried to close. “That’s another day lost.”
I told him the test was scheduled for the following day. If his coronaries were clean, we would implant the defibrillator immediately afterward.
“You’re saying one thing; other people are saying something else.”
“Well, I’m running the show here,” I said quickly. As a senior cardiology fellow, it was nice to be able to say that I was finally in charge, at least of the care of my clinic patients.
“The consent form mentioned emergency bypass surgery,” Jack continued monotone. “I don’t want that.”
That was just consent-form boilerplate, I explained. Every possible risk had to be included on the form in the unlikely event of a serious complication.
“My life was fine until you came in and started pushing your weight around,” Jack said, trying to sit up.
“I think you’re misinterpreting.”
“It’s my life!”
“Of course it is, Jack, but—”
“No!” he screamed pathetically. “I know what you’re doing, trying to make some money off of me. Look, I’d rather die. Just let me die. I’m not afraid to die; I just want to go the right way.”
I really did feel sorry for Jack. Obviously, the last thing he wanted to admit is that he needed me or modern cardiology to keep him alive. But there wasn’t much more I could offer apart from the technology with which I had been trained. And though I still wasn’t sure that a defibrillator was the right choice, once the decision was made, there was no point in ambivalence.
“I’m trying to help you, Jack,” I said, sitting down. “I’ve done everything you’ve asked me to. I even reached out to Dr. Null”—the natural healer—“for his treatment protocol, but he wouldn’t take my call. His assistant said he doesn’t even know who you are.”
(Null, I later learned, was a well-known alternative-health practitioner who denied that HIV causes AIDS, was opposed to vaccinations, and peddled dietary supplements he produced to treat various serious disorders, including cancer.)
“How is that my fault?” Jack barked.
“Look, Jack, I don’t want to make you do something you don’t want to do,” I said, close to gi
ving up. “I thought you wanted the device. If you didn’t want it, you shouldn’t have come to the hospital. You’ve wasted a lot of effort for nothing.”
Outside the curtain there was rustling, probably an intern listening in. Jack straightened up. “I told you from the beginning that I thought you were too dogmatic,” he said. “Unfortunately, your medications didn’t work, and now we’re back to where we started. I don’t blame you; you’re used to telling people what to do. But it isn’t going to work with me.”
But, in the end, it did work. After getting a shot of Ativan, Jack appeared soothed and agreed to proceed with the implant. By then, I think he knew there were no other options available to him. But, pointing his finger at me in mock anger, he said, “If I hear you bragging that you finally got me, I’m going to get you.”
* * *
In the decades after George Mines’s trailblazing work in cardiac electrophysiology, electricity became widely available in industrialized countries. By the 1930s, 90 percent of urban residents in the United States had access to electrical power. From streetcars to lightbulbs to household appliances, electricity revolutionized the way people lived. Of course, by then scientists knew that electricity powered the heart, too. But when the heart’s wiring failed, could man-made power be used to control the heart like any automatic dishwasher? This was a challenge that occupied a generation of researchers.
One of the first steps to meeting this test was taken by the cardiologist Paul Zoll at Beth Israel Deaconess Medical Center in Boston. During World War II, Zoll was assigned to an army hospital in England, where he served as the cardiologist on a surgical team. As he watched trauma surgeons remove shrapnel from soldiers’ hearts, Zoll was struck by how excitable the heart muscle was. “You just touch it and it gives you a run of extra beats,” he wrote. “So why should the heart that is so sensitive to any kind of manipulation die because there’s nothing there to stimulate [it]?”
After the war, Zoll set out to treat patients with complete heart block, a common condition in which the heart’s conduction system becomes diseased. In complete heart block, normal electrical impulses from the atria do not reach the ventricles. The ventricles, the main pumping chambers, must generate their own rhythm through a backup pacesetter that is usually much slower than the atria’s. Patients with heart block often have a dangerously slow heartbeat. They are frequently short of breath and fatigued. They sometimes faint because of low blood flow. In rare cases, they may experience cardiac arrest and sudden death.
In his first experiments, Zoll slid an electrode down the esophagus of an anesthetized dog, positioning it a few centimeters from the left ventricle to maximize the electrical stimulus to the heart. To his amazement, he found that he could capture the heartbeat with an externally generated impulse. Zoll realized that in an emergency, there would be no time to pass an electrode into the mouth and down the food pipe of an unconscious patient, so in his next set of experiments, he dispensed with the esophageal electrode and applied electrodes directly to the chest. The chest electrodes worked, too; they just required a larger current to pass the electricity through the ribs and chest muscles. The timing of the external impulses had to be perfect, however; stimulating the heart during the vulnerable period could cause it to fibrillate. So Zoll created algorithms to properly trigger the stimulus from an EKG tracing.
External pacing worked in human volunteers, but it was torturously painful. The electric current would cause agonizing contractions of the chest muscles and quickly blister and ulcerate the skin. Moreover, like the rest of the hospital, external pacemakers were powered by the municipal electrical grid. Power cords had to be strung along hospital corridors and even down stairwells when patients wanted to ambulate. The grid was prone to shutdowns and failure, hardly reassuring when treating a pacemaker-dependent patient with complete heart block. External pacing was therefore only a short-term therapy for heart block.
For a more durable solution, a revolutionary idea emerged: to implant a pacemaker inside the body, allowing it to deliver a stimulus directly to the heart rather than to the chest muscles. The heart has few sensory nerve endings, so intracardiac pacing would not be painful. Moreover, powered by its own battery, an implantable pacemaker could be long-lasting and more reliable.
The concept of direct cardiac pacing materialized in a familiar place: the Department of Surgery at the University of Minnesota. Walt Lillehei, the pioneer of cross-circulation, was learning that conduction block was a frequent complication of his open-heart surgeries, either with cross-circulation or, after 1954, with the heart-lung machine. Suturing a ventricular septal defect could sever conduction pathways or cause enough tissue inflammation to disturb the pathways temporarily. During a morbidity and mortality conference at the university in 1956, a physiologist suggested that directly pacing the heart through an electrode on the heart’s surface could rectify this problem. It would allow stimuli to be delivered to the heart at much lower voltage and be more dependable than external pacing of the chest wall.
Lillehei’s team took this idea to the lab in Millard Hall. They created heart block in anesthetized dogs by passing a suture around the top portion of the ventricular conduction system. As expected, the dogs’ heart rate quickly plummeted. They then stitched a wire into the outer wall of the heart, connected it to a pulse generator, and found that the heart rate picked right up.
After experiments with some fifty dogs, Lillehei used this “myocardial wire” for the first time in a human being on January 30, 1957. The six-year-old girl developed heart block during repair of a ventricular septal defect. With the wire in place and connected to a generator, the girl’s ventricular rate increased immediately from thirty to eighty-five beats per minute, and she survived the operation. Lillehei was soon using the myocardial wire whenever a patient showed signs of heart block during or after open-heart surgery. His device was the first electrical instrument left inside the human body for any extended period, and it worked beautifully. However, it too was only a temporary fix because the wire had to be brought out of the chest through a surgical incision to be hooked up to a generator, thus creating a possible site of infection. It was designed to treat short-term, postsurgical heart block, albeit more effectively than external pacing.
Like much of what Lillehei did as a surgeon, there was no precedent for the myocardial wire. There was no way of knowing up front that it would work, that it wouldn’t cause a host of complications—infection, bleeding, scarring—that putting a piece of metal inside the human body and leaving it there, tunneling a portion of it out through a break in the skin that could serve as a portal for germs, wasn’t totally ridiculous. It was impossible to know any of this without trying. But Lillehei, more than any doctor of the twentieth century, specialized in trying the outlandish.
A long-term solution to complete heart block was needed, however. Older adults frequently develop chronic heart block because of myocardial infarction or age-related scarring and may require pacing for months, even years, to remain alive. Between 1957 and 1960, research groups from all over the world raced to design and test a fully implantable pacemaker. But in the end, Wilson Greatbatch, an unassuming electrical engineer at the University of Buffalo, was the first to succeed.
As with so many great cardiac innovations of the past century, the inspiration for Greatbatch’s invention was a mistake. In the early 1950s, Greatbatch was working on a livestock farm near Ithaca, New York, testing instruments to monitor heart rate and brain waves in sheep and goats, when he learned about heart block from two surgeons doing a summer research sabbatical there. “When they described it, I knew I could fix it,” Greatbatch later wrote. A few years later in Buffalo, Greatbatch was working with the newly invented transistor when he accidentally installed a resistor into a circuit he was testing, causing it to give off a signal that pulsed for 1.8 milliseconds, stopped for a second, and repeated—a rhythm that mimicked the human heartbeat. “I stared at the thing in disbelief and then realized this was
exactly what was needed to drive a heart,” Greatbatch wrote. “For the next five years, most of the world’s pacemakers used [this circuit], just because I grabbed the wrong resistor.”
In the spring of 1958, Greatbatch visited Dr. William Chardack, chief of surgery at the Veterans Affairs Hospital in Buffalo, to explain his idea. Chardack was enthusiastic. “If you can do that, you can save ten thousand lives a year,” he told Greatbatch. So Greatbatch went back to his workshop and fashioned a prototype device out of two Texas Instruments transistors. Three weeks later, Chardack implanted it into a dog. The two men watched in awe as the tiny device took over the heartbeat. “I seriously doubt if anything I ever do will give me the elation I felt that day when my own two-cubic-inch piece of electronic design controlled a living heart,” Greatbatch wrote. From antiquity to modern times, philosophers and physicians had dreamed of taking charge of the human heartbeat. And finally it was possible, using simple circuit elements that were widely available. It was a seminal moment in the history of science.
However, Greatbatch’s device had problems. It was sealed with electrical tape, so body fluids caused it to malfunction after a few hours. “The warm moist environment of the human body proved a far more hostile environment than outer space or the bottom of the sea,” Greatbatch wrote. So he worked to cast the electronics in solid epoxy to make them more impervious, thus increasing their life span to four months. With no external funding, and splitting his time between Chardack’s crowded lab and a small workshop in the barn behind his house, Greatbatch worked on the critical problems standing in the way of permanent cardiac pacing: battery life, proper insulation, and rising stimulation thresholds requiring higher and higher current to control the heart over time. (In the process, Greatbatch invented the first long-lasting lithium battery, still in use today.) By the late summer of 1959, Greatbatch had used up his personal savings of $2,000 to handcraft fifty implantable pacemakers. Forty were tested on animals; the remainder went into humans. The first human implant took place on April 7, 1960, in a seventy-seven-year-old man with complete heart block. He survived for eighteen months. The wires were hooked up to the outer wall of the ventricle, but later, using techniques developed by Wilfred Bigelow, the Canadian surgeon who pioneered surgical hypothermia, wires were passed through veins and directly into the heart. The Chardack-Greatbatch pacemaker worked remarkably well. One of the first patients to get one was electronically paced for more than twenty years and died in her eighties.
Heart--A History Page 15