7 Search for Diffusion Limitation in Pulmonary Gas Exchange Johannes Piiper, M.D. Director, Department of Physiology, Max Planck Institute for Experimen­ tal Medicine, Gottingen, Germany I dedicate this chapter to the memory Estonia in the Russian Empire. With the of those who introduced me to physiology support of well-off relatives, he was able and guided and promoted me through the to complete secondary school in Tallinn years: Wolfgang Schoedel, long-time head and study biological sciences at the Uni­ of the Department of Physiology and my versity of St. Petersburg. He became pro­ predecessor; Kurt Kramer, head of the De­ fessor of zoology at the University of Tartu partment of Physiology at Gottingen Uni­ when it reopened as an Estonian univer­ versity (later at the University of Munich) sity in 1919, after Estonia had won its and my academic promoter, whose enthu­ independence from czarist Russia after siasm for physiology inspired me; and fighting both the Germans and the Red Hermann Rahn, of Buffalo, New York, Army in the years following World War I. who was unsurpassed as a questor of I was born in 1924 and grew up in a things physiological. free country during a peaceful time of economic growth and cultural develop­ From Estonia to Germany, ment. All this came to an end with the Through War and Peace establishment of Soviet military bases in Estonia in the fall of 1939 and the annexa­ My father was born in a poor family in tion of Estonia by the Soviet Union in the Tallinn, capital city of the Government of summer of 1940. After the onset of the From: Wagner WW, Jr, Weir EK (eds): The Pulmonary Circulation and Gas Exchange. ©1994, Futura Publishing Co Inc, Armonk, NY. 125 126 • THE PULMONARY CIRCULATION AND GAS EXCHANGE German-Soviet war in June 1941, many charged. But a fellow professor of my fa­ Estonians were arrested and deported to ther had come as refugee to Gottingen and northern Russia, and young Estonians searched for me by advertising in a refugee were drafted into the Red Army. Being one newspaper, which was smuggled into the year too young, I escaped the draft. camp. Finally , by the end of 1946, I was The German forces advanced quickly, discharged along with a number of Estoni ­ but when they reached Tartu, they were ans , Latvians, and Lithuanians . The rea­ halted for several weeks by the river that son I went to Gottingen , where a large flowed through the city. During that time a camp for Baltic refugees was located, was large part of the city was destroyed by the that I wanted to enter the university's fires resulting from artillery shelling and medical school. This had been my par­ arson by Red partisans. In 1942 I gradu­ ents' wish, and I never hesitated to comply ated from secondary school in Tartu, after with it, although I was attracted more by which I had to join the Luftwaffe, first as biology than medicine. an auxiliary serviceman, but soon thereaf­ I had lost all my documents including ter as a regular soldier stationed in Esto­ school certificates, and it was utterly im­ nian territory. possible to obtain substitutes from Esto­ As the German army retreated from nia . All I could do was procure written the Baltic countries in September 1944, declarations from two of my former teach­ my unit was shipped across the Baltic to ers who had come as refugees to Germany. East Prussia. I was wounded on the out­ But the main reason I was accepted was skirts of Konigsberg, escaped from the en­ the extraordinary considerateness of circled city on horse cart, and was taken Gottingen University's counselor for for­ on board a hospital ship to the port of eign students, Dr. Wienert, who, after hav ­ Sassnitz on Ri.igen Island. There the less ing heard my story, arranged my admission seriously wounded were immediately dis­ pending my passing an oral admission ex­ embarked and taken on a hospital train. amination. Because of my long absence The severely wounded stayed on board from school and my poor mastery of scien ­ the ship, which left the port and headed to tific German , this was the most difficult the roadstead for safety, but it was hit by exam I have ever taken. My examiner in bombs dropped by Allied aircraft the fol­ mathematics and physics was Professor lowing night and sank with all the se­ Hans Loeschcke, the well-known respira­ verely wounded. My remarkable luck was tory physiologist. I remember one of the that, though graded as severely wounded, problems he gave me was determining the I had been helped by lightly wounded height of Egyptian pyramids using a yard­ German soldiers to the train, thereby es­ stick but without climbing the structures caping the shipwreck. During the follow­ (Luckily I had always been good in geome­ ing four days the hospital train traveled try.) across the whole of war-torn Germany, With much luck I had survived the from north to south. Finally we stopped war and was admitted to medical school, near Garmisch-Partenkirchen in Bavaria but I was alone . My parents and my sister and were put into an auxiliary hospital. remained in Estonia. I received some sup­ Soon after American forces occupied port from Estonian refugees, and I lodged Bavaria, my wound had healed suffi­ clandestinely in a Displaced Persons' ciently, and I was taken to an American camp supported by refugee organizations. prisoner -of-war camp in Garmisch-Parten­ I could not obtain official permission to kirchen. Being Estonian, I could not be stay there, because of my military past. released due to lack of regulations, Later I was admitted to a student home whereas Germans were continually dis- supported by a Lutheran church organiza- Diffusion Limitation • 127 tion. After finishing two and a half years of the Estonian University of Tartu). I was my preclinical studies, I applied for immi­ fortunate to find in Pierre Haab not only gration to the United States but was de­ an indispensable coworker in Buffalo, but nied because of my military involvement also a scientific companion and a friend on the wrong side. About one year later I for life . was requested to come to an emigration I learned that the alveolar-arterial P 0 ) camp for a new interview, but then I was difference (AaD0 was conventionally at~ the one who declined, intending to finish tributed to three fuechanisms: ventilation­ medical school in Germany. perfusion (VA/Q) inequality, shunt, and After passing the state medical exami­ diffusion limitation, which were not eas­ nation I looked for a place to work and to ily differentiated (Fig. 1). Hermann Rahn's prepare my medical doctor thesis. After idea was to demonstrate the effect of venti­ some unsuccessful applications, I was in­ lation -perfusion inequality by an experi­ troduced by Professor Loeschcke to Pro­ ment that had a simple and straight ­ fessor Schoedel, the director of the physi­ forward design but could not be easily ology laboratory of the research institute performed. According to Far hi and Rahn 10 (later named the Max Planck Institute), the AaD0 due to VA/Q inequality should where I was accepted in January 1953. An be much 'reduced when N2 is eliminated important asset was that I could get a from inspired gas. This could be achieved fellowship, worth about 100 German by breathing 100% 0 2 in a hypobaric marks a month , which at that time and in chamber at a total pressure reduced to my circumstances was a good income. I such a level that alveolar and arterial P 0 never felt as rich since then. Today I am stayed normoxic, i.e ., at a total pressure of still working in that institute , and since about 197 Torr, equivalent to 10 km of 1973 I have served as director of the De­ altitude. The result of the exciting experi­ partment of Physiology. ments we carried out, with all three of us (the experimental dog, Pierre Haab, and myself) confined in the hypobaric cham­ Steady-State Gas Exchange: ber for many hours, was unexpected and Diffusion Limitation versus disappointing: the AaD0 in anesthetized, Ventilation!Perfusion artificially ventilated dJgs remained un ­ Inequality and Shunt changed after elimination of N2 from in ­ spired gas.17 We considered several possi­ In September 1958 I came to the ble "loopholes" such as incomplete elimi ­ United States to work for one year with nation of N2 , accelerated development of , Hermann Rahn in the Department of Phys­ atelectatic shunt in the absence of N2 and iology at the University of Buffalo , later V)Q inequality of a mainly alveolar dead called the State University of New York at space -like character (the AaD0 due to al­ Buffalo . The timing was awkward because veolar dead space would be little affected my wife was expecting our first child, and by elimination of N2). We also considered I could not afford to take her to the United the possibility that the AaD0 in dogs in States. In Buffalo, I was introduced to the our experimental conditions ~as not due American way of life and to the analysis of to VA/Q inequality but to another kind of pulmonary gas exchange by Pierre Haab, maldistribution, unequal distribution of who had come to Rahn from the laboratory diffusing capacity to blood flow (D/Q ine ­ of Alfred Fleisch at Lausanne a year ear­ quality) (Fig. 2). 44 lier. (An interesting coincidence is that I had developed the concept of D/Q Fleisch had invented the pneumo­ ratio to explain the experimentally deter­ tachograph as professor of physiology at mined absorption rates of inert gases of 128 • THE PULMONARY CIRCULATION AND GAS EXCHANGE IDEAL DIFFUSION LIMITATION A v a v a j' 7-----a 7------a r---- a l- V -V -V -V Po, Hypoxia Normoxia Hyperoxia ) Figure 1.