Solving the Mysteries of Heart Disease

by Gerald D Buckberg

  The truth is, treatments solving these problems exist.

  Readers of this book may add their voices to mine and those of my colleagues who continue to push the rock up the hill, trying to encourage the larger medical community to transform. Frankly, we owe it to our patients, our colleagues, our loved ones, and the world at large to advance this long-overdue shift. Change and evolvement are inevitable. The answers are already here.

  How long do we wait before we embrace them?

  CHAPTER 10

  Re-oxygenation Injury:

  If a Little Oxygen Is

  Good, Is a Lot Better?

  We learn the importance of oxygen at a young age. It becomes apparent the first time we try to hold our breath or discover how far we can swim underwater. Our understanding expands in grammar school when we learn that room air contains about 21% oxygen, and later, that “green tanks” of pure oxygen (100%) are used to supplement breathing, as in the oxygen tents shown in old movies.

  Yet we generally take oxygen for granted.

  Until we don’t have it.

  From the moment a newborn’s bottom is lightly spanked in the delivery room to initiate breathing outside the womb for the first time, to the hearty pink color of babies in the nursery, eyes open in animated wonder… we witness the marvel of how breathing room air, containing normal oxygen, contributes to their healthy appearance.

  Conversely, a world of sorrow emerges when these children fail to get enough oxygen. They appear dusky and blue, languishing rather than exhibiting the normal activities that characterize healthy infants.

  The causes of this can relate to heart as well as to lung conditions, and the history of cardiac surgery includes developing excellent ways to correct this problem to allow “blue babies” (called cyanotic) to become oxygenated.

  Yet among these worthy accomplishments, I would discover something startling. Though helping these babies receive increased levels of oxygen would seem a viable way to offset this problem — sometimes it made things worse. Much worse.

  My first exposure to the dilemma of oxygen being a problem rather than a cure happened when I was asked by the pediatricians to express my thoughts about an infant who had a deep blue color because her lungs were immature and had become congested. The heart itself was beating fast, but working well.

  The solution seemed straightforward. The pediatric cardiac surgeons could easily take over for the lungs and heart by using a miniature heart-lung machine. In this way, they could provide her sufficient oxygen so her stressed lungs would not have to work — they could rest, allowing them to heal.

  This was done by inserting two small tubes into the infant’s blood vessels. These tubes were connected to the small heart-lung machine, which administered its usual high levels of oxygen. Newly oxygenated red blood was pumped back into the proper artery to be distributed to the body. The infant’s coloring improved and became pink. All appeared better.

  Then to everyone’s surprise, things were not better. This child’s lungs suddenly grew more swollen from fluid accumulation (water in tissues), and the heart began not working well, contracting poorly.

  The child’s condition deteriorated despite our having delivered a treatment that takes care of what was wrong. Even though the heart and lungs were put at rest so there could be healing, their condition became worse than before treatment was started. The supposedly wonderful thing I had learned of in school that came from those miraculous green oxygen tanks — now appeared to be causing terrible harm.

  This wasn’t what we expected. It wasn’t what the parents were expecting. Obviously, they and their physicians were distressed. “How do you explain this?”

  I couldn’t.

  They had done nothing incorrectly. I could only say, “Something is occurring that we don’t understand.”

  Unfortunately, I would discover this experience was not unique. Oftentimes, when others treated blue babies in this same way, these children would develop swollen lungs, and most importantly, their hearts became “stunned” — their contraction diminished — and sometimes would completely stop beating.

  An Even Bigger Dilemma

  As it would turn out, this dire situation wasn’t the only circumstance in which providing supplemental oxygen became a problem.

  Brad Allen, chief resident of cardiac surgery at UCLA, visited my office looking preoccupied and perplexed.

  I asked, “Brad, what is troubling you?”

  He seemed frustrated as he related stories of treating children that were blue from a congenital heart defect whose hearts were then superbly corrected in surgery… only to have them develop poor heart performance, sometimes succumbing from cardiac failure. Brad recounted his painful exchanges with distraught parents whose infant now had a corrected heart, but faced uncertain survival. Brad’s question was clear.

  “What happened to twist this technical success into a potentially tragic outcome?”

  Brad had been helping to correct underlying heart defects in infants and children — both those who were blue (cyanotic, from too little oxygen), or others that were pink (having normal amounts of oxygen). But he was baffled. The duration of the operations were similar… with each infant receiving the same cardioplegic solution to prevent damage when the heart’s blood supply was temporarily interrupted… and each receiving the same elevated concentrations of oxygen on the heart-lung machine. Yet while the pink babies thrived… some blue babies were experiencing the tragedy that he described.

  Though adding a surgical operation differed from our first example of only helping the blue baby’s lungs since the heart was normal, there was one striking similarity:

  These blue babies always experienced heart damage when oxygen was delivered in high concentrations.

  The sleuthing needed to begin.

  Probing the Riddle

  As I only performed adult cardiac surgery, listening to Brad describing these problems about pediatric surgery was eye-opening. The pink children, in whom surgeons closed a hole in the ventricle, had a smooth course: heart action was normal, their lungs remained clear with normal breathing patterns, and no body swelling occurred.

  In contrast, substantial problems developed in some of the blue (cyanotic) children. Their procedures often fixed a poorly developed left ventricle, or corrected the positions of the aorta and pulmonary arteries that were in the wrong hookup position to the ventricles. The reasons for their cyanosis were corrected by a technically successful operation. But despite such benefit, the infants’ lungs became stiff (not stretching or functioning normally), and the heart and other tissue areas became swollen.

  This led to the awful situation where the child’s chest sometimes had to remain open after surgery, because closing it would put too much pressure on the already swollen, poorly contracting heart. This meant the child would remain in the ICU under careful watch, with a biologic dressing on the surface of the heart, while the organs and tissues dried out for two to three days before the chest could be closed. As you might imagine, this was a very intense and stressful situation for the surgical staff — and especially for the parents. Unfortunately, this drama was almost predictable if the infant was cyanotic before the surgical procedure.

  In every case, the child’s procedure had required the use of the heart-lung machine. Could this miraculous technology — that had literally transformed heart surgeries and helped save countless lives since the 1950s — somehow be the source of the problem?

  A Walk Through Surgical History

  The role of oxygen in modern cardiac surgery began in the 1940s, as the first operative procedures were done to improve blood oxygenation in blue babies.

  The major cause for cyanosis is birth defects in which there are holes or flaws within the heart, whereby blue blood (which has had its oxygen depleted after being used by the body) becomes improperly redirected into the arteries of the body’s circulation where red oxygen-rich blood is meant to be circulated. Because of this, cyanotic (oxygen depleted) bloo
d goes to body organs, instead of normally first going to the lungs to take up oxygen. This was a dreadful problem, as you can imagine.

  Cardiologists and surgeons could only use the tools that were available at that time; they did not have sophisticated modern X-rays, angiograms, and echograms. Yet their intuitive wisdom and sage diagnostic abilities determined there was too little oxygen in these babies. The most common defect was called tetralogy of Fallot (TOF). It was comprised of several primary defects: a hole in the septum (the muscular curtain between the left and right ventricles), a narrowing of the pulmonary artery supplying the lungs, and the thickening of the right ventricle (due to its having to now work harder.) Unfortunately, the prognosis was grim for these cyanotic children, and the pediatric community felt tremendous grief for their plight.

  But in 1944, a groundbreaking surgical approach to improve oxygenation for these children was developed at Johns Hopkins Hospital, and it overcame these limitations.

  There was a unique cast of cardiac pioneers at Hopkins during this time. This breakthrough started with Helen Taussig, a cardiologist and one of the giants of cardiovascular disease, who cared for cyanotic children that no one could help. She was desperate to figure out what was happening inside them, since all would perish at a very early age.

  Dr. Taussig’s thirst for knowledge overcame her own limitations, including dyslexia, and a hearing difficulty that prevented her from using a stethoscope, one of the most potent diagnostic tools for a cardiologist as they could listen to the beating heart. Her unstoppable creative drive was her forte, and this led her to come up with innovative ways to understand and then help these desperately ill children.

  Since these defects were genetic, she knew nature itself created the causes behind what was happening in these children, and so she did something extremely remarkable: she analyzed the baby’s evolution in the womb. This included recognizing that before they were born, the lungs of children are collapsed and do not receive blood flow to gain oxygen, since oxygen is supplied by the mother. The mother essentially becomes the baby’s heart-lung machine, because her oxygen-rich blood is diverted or shunted into the embryo’s body through a tube called the patent ductus arteriosus. Dr. Taussig properly reasoned that these infants did fine in the womb — until this ductus would naturally close after birth — at which point the baby became cyanotic.

  The baby’s own lungs were to take over at this time, but because of anatomical defects, this was not happening sufficiently. Dr. Taussig surmised that cyanosis would not have developed if the infant’s ductus had remained open, since it would have provided an alternative path for blood flow between its body and lungs that would have compensated for the baby’s defect. That was not possible because the ductus closed at birth, certifying that nature didn’t intend it to remain open.

  Dr. Taussig asked, “Is there a way medical science can make a substitute?”

  As I’ve always appreciated, the beauty of the university is that within its walls lives an abundance of innovative, dedicated people, whose individual talents may blossom further through interaction with colleagues from another field of study. This marvelous blending of gifts existed at Hopkins, where the Chief of Cardiac Surgery was Alfred Blalock. He possessed a creative intellect and was a titan in his field, and I would later have the good fortune to learn from him when I came to Hopkins in the 1960s.

  Before arriving at Hopkins, Dr. Blalock had done experiments at Vanderbilt University where he created a shunt (hookup) that connected a branch of the aorta (the body’s main artery) to the pulmonary artery (which normally carries oxygen-depleted blood to the lungs). He was trying to increase the lung blood pressure. But even though the operation worked well technically, his hookup couldn’t raise blood pressure in the lungs. This was due to a natural adaptive mechanism in the body in which, under normal conditions, only the lower part of the lung receives blood flow. This sets the stage for exercise, during which increased blood flow would enter the whole lung, and not burden the lungs with high pressure. This natural adaptation for allowing an amplified blood flow in the lung, prevented Blalock from achieving his expected results and caused him to abandon this pursuit.

  At Hopkins, Dr. Taussig came to Dr. Blalock with her theory about what was happening with her cyanotic children, hoping a surgical solution to the problem could be found. After listening to her observations, Dr. Blalock said, “Helen, it sounds to me like you’re looking for a substitute ductus to replace the one that nature closed. It so happens that I have made such a ductus. While it did not increase blood pressure in the lungs as I had intended… it did significantly increase blood flow to the lungs.”

  The First-Ever Innovative Procedure

  The reader needs to appreciate that until this time — ten years before the invention of the heart-lung machine — no one was operating on hearts. It was believed to be impossible. At the same time, one couldn’t help but become terribly saddened upon seeing the suffering of the many blue babies under Dr. Taussig’s care. These children had no reprieve from a death sentence due to their defects.

  Dr. Blalock took on the challenge.

  Before conducting this trailblazing surgery on a patient, there needed to be experimental evidence that this shunt could work in a cyanotic subject. Yet this task of creating cyanosis in an animal test subject had never been accomplished.

  This assignment fell onto the shoulders of Dr. Blalock’s highly gifted lab technician and colleague, Vivien Thomas. Thomas was himself a pioneer, having demonstrated phenomenal insight and surgical abilities despite having never gone to medical school, and during a time when such opportunities in the lab did not exist for African Americans. In fact, the splendor of the relationship between these two colleagues was highlighted many years later in the television movie, Something the Lord Made, which received great acclaim (including nine Emmy Award nominations and the win for Outstanding TV Movie).

  After numerous frustrating attempts, Thomas finally managed to make an animal subject develop cyanosis, and together, he and Dr. Blalock showed that this shunt could counteract the cyanotic condition.

  It finally came time to perform the operation on a baby.

  The first infant underwent the operation in 1944, but the road to success was not smooth, as the administrators at Hopkins denied all African Americans access to the operating rooms. Dr. Blalock cast aside these “social traditions” and demanded that Vivien stand alongside him to oversee the technical aspects of this procedure.

  Meanwhile, some of the Hopkins staff in attendance to observe the procedure voiced skepticism, holding fast to the conventional belief that surgery on the heart was simply not feasible.

  Yet it was the surgical team’s actions — not the rigid conceptual barriers — that took center stage. The drama of success was instantaneous, as opening the shunt made the baby’s blue color immediately change to pink!

  This extraordinary procedure was named the Blalock-Taussig shunt and it initiated the modern era of cardiac surgery.39 The world welcomed the chance to learn this stunning approach, and Dr. Blalock traveled the globe to teach it to others.

  Building on Their History

  Many years after this breakthrough event, I remember donning my “white suit” to start my medical life as an intern at Johns Hopkins Hospital. On that first day in 1961, I was awed to enter the Center for Surgical Sciences building (today called the Blalock Building). It represented a magical world to this 26-year-old. The elegant lobby displayed beautifully framed photos of past chief residents, a historical panorama that included the most famous heart surgeons in America, who had started at this very place where heart surgery originated. Certainly, this kid from the Bronx could have been intimidated, questioning if his abilities would ever match theirs. Could I carry on their legacy? But mostly I was hungry for learning, feeling fortunate and grateful to be at one of the world’s preeminent hospitals! Walking through these hallowed halls was exhilarating.

  From here, I went upstairs to the floor a
bove the operating room, where interns and residents would take lunch. The menu was simple: saltine crackers, peanut butter and jelly, and soup. We were paid $45 per month. Across from me at the luncheon table was an English resident in orthopedics, who was perplexed by the traditions of Hopkins. Quenton said, “Gerry, I do not understand this place with its 150-year history and heritage displayed by a bevy of paintings of past pioneers. My English hospital is 750 years old, yet we do not tarnish the walls with such graphics.” An interesting perspective, but it overlooked the importance of honoring those who had laid down stepping stones toward the future; the paintings were not simply there to provide a stroll down memory lane.

  The impact of being at Hopkins at this time was profound. I remember my first impression of Helen Taussig. She appeared grumpy and did not communicate with surgical residents. But when she walked the halls of Harriet Lane (where pediatric patients were cared for at Hopkins), she was surrounded by a concert of cardiology residents and fellows hanging onto her every word.

  Yet the truth of a person is not always visible from such external visual clues, just as the surface of the heart does not always reveal what is occurring within it. That truth is borne of performance. Dr. Taussig’s clinical analysis of cyanotic children changed their lives and changed history, and her actions launched the field of pediatric cardiology. Her unyielding passion to create an innovative treatment let her cross the “impassable aisle” between cardiologists and surgeons to jointly champion the Blalock-Taussig procedure.

  Equally impactful is that my internship at Johns Hopkins Hospital occurred while the Chief of Surgery was Alfred Blalock. Inspiring, logical, and wise, Dr. Blalock became a role model who had an enormous influence on my career.

  For me, history and tradition became dramatically fused during an early experience in the operating room. As a young intern, it was astounding to have the chance to scrub in and stand alongside of Dr. Blalock, one of the greatest surgeons in the world, as he was about to perform his renowned shunt procedure on a blue baby. Traditionally, everyone in the operating room wears green scrub suits, but upon entering the OR, I saw the anesthesiologist was an elderly, frail lady dressed entirely in white. I wondered, “Who is she and why the white uniform?” I was told she was Olive Berger — who had performed the very same task, also while wearing white — when Dr. Blalock first conducted the procedure in 1944.