My Initiation into Respiratory Physiology

ARTHUR B. OTIS

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I do not regard the paper, "Venous pressure changes associated with positive intrapulmonary pressures; their relationship to the distensibility of the lung" (American Journal of Physiology 1946;146:307-317), as my most important publication. I have chosen it because it represents the beginning of my career as a respiratory physiologist. In this research I measured changes in venous pressure, intrapulmonary pressure, and lung volume in human subjects performing various maneuvers. The published paper begins with a formal analysis of the expected relationship among these variables as though I knew from the beginning what I was doing. The truth was quite different.

To give a little background, the time is a period of years beginning in the fall of 1942. The place is the department of physiology at the University of Rochester College of Medicine. The principals are Chairman Wallace Fenn, Hermann Rahn, and myself. The United States was then a participant in World War II. President Roosevelt had established the Office of Scientific Research and Development (OSRD) to mobilize and coordinate scientific and medical research relating to national defense. Wallace had a contract with the OSRD to study physiological effects of positive pressure breathing, a maneuver that was hoped to give the fliers in our Air Force a few extra feet of altitude tolerance.

I knew very little about human respiration. I had not had, and to this day have not had, a course in human physiology. On the day I arrived in the Department, Wallace led me into a laboratory where an experiment was in progress. Shortly, a graduate student had fitted me with a mouthpiece and nose-clip, turned on the positive pressure and told me to breathe. This was my introduction to respiratory physiology.

Hermann Rahn had arrived some weeks earlier than I, and had already made a number of measurements of relaxation pressures in human subjects to obtain the pressure-volume relationship of the chest and lungs acting passively as a unit. One day Wallace suggested that I make measurements of venous pressure of subjects breathing positive pressures. The object was to find out whether venous return might be seriously compromised. I first tried to use an indirect method using some equipment designed for a student laboratory exercise but shortly abandoned it as unsatisfactory. I knew that venous pressure was measured clinically with a saline-filled manometer connected to an intravenous needle. I had never stuck a needle in anyone's veins before, but I had cannulated a lot of oyster hearts, so I rigged up a saline-filled manometer system, found a subject (a cooperative graduate student) with prominent antecubital veins and discovered that measurements in resting subjects breathing quietly were not difficult. However, a liquid-filled glass tube manometer does not respond very rapidly to pressure changes.

There was in the laboratory an excellent motor-driven recording camera with which continuous records could be made on 6-inch-wide paper by focusing a light beam on the camera slit. With stuff I found lying around the laboratory I rigged up a liquid-filled optical manometer for recording venous pressure and a similar air-filled one for breathing pressure. The optical manometers were put together using rubber membranes chosen by trial and error to be of appropriate stiffness. Near the edge of each membrane I glued a chip from a one meter length galvanometer mirror. Primary light sources were slit lamps powered by projector bulbs. The system worked, but to get useful records I had to make sure that the light sources, mirrors, and camera slit were properly aligned at the right distance and then calibrated with a water manometer. With care and good luck we obtained excellent records, but an experiment could be ruined by a careless elbow jarring an optical system out of line, by a light source burning out, by running the camera without making sure its slit was open, that its paper supply had not run out, or by a subject moving in such a way as to occlude the intravenous needle. Fortunately, we managed to avoid such incidents for the most part, but they did happen occasionally and so a morning or afternoon was sometimes wasted and chalked up to experience.

At first I was more concerned with the techniques and accuracy of the measurements than with interpreting them.

Using the technique just described, I measured venous pressure while varying intrapulmonary pressure in various ways. Voluntary relaxation pressures at various lung volumes provided steady-state measurements. Hermann was my favorite subject for these because he was experienced in the art of relaxing his breathing muscles at various lung volumes. Starting at the end of a normal expiration, he could inspire or expire a measured volume, relax his breathing muscles and maintain the relaxed state until a steady state of venous pressure had been achieved. I also made venous pressure measurements on several subjects breathing from two types of demand regulators. One type maintained a nearly constant pressure at some desired preset level. The other type delivered air cyclically, starting at ambient pressure, gradually increasing to a preset maximum, then dropping exponentially back to ambient.

Gradually it became clear to us that if lung volume was held constant, venous pressure rose by an amount equal to the positive pressure applied to the lungs, but if the lungs were allowed to expand, venous pressure rose by about half the applied pressure. We concluded that the other half of the positive pressure was absorbed by the elastic forces of the lungs as they responded to the positive pressure by expanding.

Under the gentle guidance of Wallace Fenn, Hermann and I worked closely, congenially, and effectively as colleagues. Our temperaments seemed complementary. We shared ideas and were mutual critics. Each of us took primary responsibility for certain projects but we participated in almost all of them as subjects, or investigators, or both. Hermann and I often spent time at the blackboard (we seemed to think better while holding a piece of chalk) discussing experimental results, plans for further experiments, or clarifying concepts that were bothering us. We were both novices as far as human respiration was concerned. We hadn't had much experience in thinking about partial pressures of gases or the effect of water vapor on the partial pressures of oxygen, carbon dioxide, and nitrogen, but after a few blackboard sessions, making the necessary corrections became automatic.

We were confused at first by negative pressures. How could a pressure be less than zero? After considerable discussion we came to realize that a pressure could be considered negative if it were less than some reference pressure. Such a simple concept eluded us at first but it soon became a part of our everyday comprehension. Of course Wallace Fenn could have set us straight when such questions first arose, but I suppose we were too proud to ask him. Moreover, he may have thought we would have a better grasp of such concepts if we figured them out for ourselves. I believe Hermann and I were not exceptionally stupid, but we were certainly naive.

One day Hermann and I had a blackboard session discussing the results of the venous pressure measurements. I had originally thought of them only for the significance they might have for the circulation. Hermann, who had more intuition than I, suddenly came up with "You ought to be able to get a good estimate of lung tension from these data." Lung tension was the term we used to denote the elastic force opposing lung expansion. It is equivalent to "transpulmonary pressure."

After our chalk session I thought about it some more and plotted some graphs, the initial versions of those shown in the eventually published paper. We concluded that, although our data by itself could not get us an absolute value for lung tension, it did allow a reasonable estimate of changes in lung tension with changes in lung volume. We had become addicted to graphical representation and analysis of physiological events. Movements from point to point on a set of coordinates had become as real to us as the movements of anatomical structures, even more so in a sense. Humans (some of them at least) seem highly dependent on symbolism.

Projects supported by the Government were classified as to degree of confidentiality; "Top Secret," "Secret," and "Restricted" are the categories I remember. Our project was classified Restricted and publication in the open literature was forbidden. We were expected not to talk in public about what we were doing, but we were not subject to anything like the secrecy imposed on the Manhattan project. We were required to make brief summary reports to the OSRD which distributed them to other laboratories working on related projects, and Wallace Fenn went to occasional meetings with other OSHD investigators for informal exchanges of information. Hermann and I made two or three visits to other laboratories with related interests. No meetings of the America Physiological Society were held in 1943, 1944, and 1945. We were not concerned about priorities. We did want to obtain useful information and naturally hoped to he recognized by our peers as doing good work.

I might say parenthetically that I believe our country was more unified during the World War II period than at any other time in my experience.

When the War was over, our work was declassified and we were free to publish in the open literature. The work on venous pressure was done in 1942. The resulting paper was published in 1946. By that time I thought I had the subject well in hand. However, I could still make stupid mistakes. In the paper I used the term distensibility when I really meant its inverse, elasticity. For whatever reason no editor or reader has ever pointed the error out to me.

This paper was not was not a great contribution to the big world of science. It was important to me. I had discovered that I could play the game.

	Footnotes

Correspondence and requests for reprints should be addressed to Arthur B. Otis, Ph.D., Professor Emeritus, Department of Physiology, University of Florida College of Medicine, 2123 NW Fourth Place, Gainesville, FL 32603-1515. E-mail: abotis2094 @aol.com