The carbon monoxide story. Part 1.1
Continued from Part 1.0
“Sorry Joe, I don’t think that will work at all.” I was walking along the ground level corridor at Toronto General Hospital with Dr. Noe Zamel, respirologist, and the head of the TGH pulmonary function lab, and a longtime colleague at the Thursday afternoon Respiratory Physiology seminar sessions in room 2022-3 the Medical Sciences building. I had given him my elevator pitch about how hyperventilation would accelerate the elimination of CO. His first question was “Why in the world would you think that?” I said “Well, the CO is bound to the hemoglobin but diffuses into the alveoli until the ‘partial pressure’ comes into equilibrium with that in the red blood cells. The greater the volume of oxygen that washes through the lung, the more CO will diffuse off the hemoglobin and be eliminated. QED”
He shook his head again, “Makes some sense but the order of magnitude is way off. No matter how poisoned the blood, the amount of CO in the lung is teensy-tiny compared to that on the blood. No matter how much hyperventilation you do, the amount of CO you will get rid of negligible. Sorry, Joe, as I said, I don’t think it will work.”
I passed the idea by some other colleagues and got similar responses. Then I asked my friend Dr. Ludwik Fedorko, who was also an anesthesiologist in my department. His take: “Crazy idea, but might just work. Lets try it”. I don’t know which answer was right but I liked Ludwik’s the best. Plus he said the word “lets” which meant he will help. I discussed it with Dr. Steve Iscoe, who as a professor of Physiology at Queen’s University in Kingston Ontario, was my mentor, editor, and, truth be told, unofficial supervisor throughout the studies we were doing on the tracheal motility. He discussed the “pro” and “con” issues but concluded: “we won’t know until we try it.” So it was a “go”.
It was 1997 and in those days TGH had animal labs in the basement of the College wing. The entrance to the labs was a nondescript door on the main floor with a numeric coded entry. One then climbed down some poorly lit dingy stairs to something that looked like a series of Crusader castle dungeons, but may have been built as air raid shelters during WWII. Anyway, I had an animal ventilator and other equipment from my tracheal tone work. We even had a source of CO. In turns out that tanks with very dilute CO (0.3% in air) are used for some pulmonary function tests. So I ordered a tank.
We needed one more thing: CO blood tests for blood concentrations of how much CO was attached to the hemoglobin. I went to the TGH hematology and biochemistry lab and found Jerry who ran the lab. I told him what I needed. He told me he can’t do it as each blood test must be tied to a patient medical number for billing. I told him of my idea and that ‘if it worked we would change the practice of medicine for humanity’ and he would retain a place in the story. He was very sympathetic and was suffering under my pressure. Eventually, he relented a bit and said that he may be able to hide 3-4 blood tests. Well, it was a start. What’s more, it justified going ahead with the experiment. I was on call on the Thursday. As we were most often up all night when we were on call, we were automatically given the next day off. Friday would be our D-Day. I rallied the students and notified Ludwik.
I don’t remember if I was up all night on call, but on that Friday, we started early in the morning. We placed an i.v. catheter in a paw and anesthetized the dog, intubated it, put it on the ventilator. The students assembled the device that would keep the PCO2 in the normal range as we turned the dials on the ventilator to change the breathing frequency and breath size. We drew some baseline blood samples and began to expose the dog to CO. We had no idea as to how fast the CO would go up in the blood and to what extent the dog would tolerate it without dying. We drew blood samples about every 5 minutes and ran them to the lab for Jerry to run them through the analyzer. After about 70% of the hemoglobin was occupied by CO we stopped the exposure and allowed the dog to be ventilated with room air. After a few blood samples, we switched the inhaled gas to pure oxygen and took some serial blood samples. We then hyperventilated the dog and took more samples over about an hour. The 3-4 samples that Jerry agreed to were used up in establishing the degree of poisoning. These other samples taken every 5 minutes during “treatment”, were labeled and placed in a plastic zip-lock bag.
At the end of the experiment, we euthanized the dog and cleaned up. It was now late Friday afternoon. I sent everyone home and took the bag of syringes to Jerry’s lab. It turned out that Jerry was working the evening shift and was alone in the lab. “Uh Jerry, we need these analyzed” I said pointing to the bag full of syringes. “Joe, I will lose my job!” he pleaded. I offered a smattering of responses: “Jerry, I will replace all reagents…no one will know (“uhh, yes they will, there is a counter on the machine”)…charge me for the tests…blame me…say I forced you …say that I snuck in and ran the samples without your knowledge…the 30 samples are a mistake in the counting software of the analyzer;” and I threw in a whole bunch of “..we are on the verge of a huge breakthrough…this will save thousands of victims of the most common cause of poisoning in the world…” . Finally he grabbed the plastic bag with the syringes out of my hand and told me to get out of his lab and come back in an hour. Good as his word, when I returned he gave me a hand-written table with a column of syringe numbers, and opposite each number, the level of carboxy-hemoglobin. I grabbed the list and rushed home.
The list sat on my desk at home all of Friday night, and Saturday. Sunday morning, my stomach in knots, I took out a piece of graph paper. I used a ruler and a pencil and drew in a horizontal axis which I labeled “time”. I then drew the vertical axis, and labeled it “[COHb]%” (which stands for carboxyhemoglobin, that hemoglobin poisoned by CO). I then began graphing the numbers on the table, one by one. I used a ruler to find the time on the X axis and turned the ruler horizontally and drew it up until it crossed the number on the Y axis designated in the table, and there I penciled in a dot. Soon the dots were accumulating on the graph. I tried not to look at the trend until I was done, but my heart began to pound and my underarms began to sweat. Then, to be doubly sure, I re-graphed the data on log-linear graph paper, which turned the rate of CO elimination into a sloping straight line. The steeper the slope, the faster the elimination. As I got close to graphing the final points, my hands were trembling and my under-arms were drenched with the sweat running down the side of my chest under my shirt. I said out loud: “Holy shit! Will you look at this!”
Read more in Part 1.2
