10427_macklem.qxd 02/10/2007 11:04 AM Page 383 SPECIAL ARTICLE Canada’s contribution to respiratory physiology and pathophysiology Peter T Macklem MD t is an almost impossible task to describe Canadian contribu- that clinical research was part of his training program, and as a Itions to respiratory physiology and pathophysiology. There result, Christie published a series of classical papers in respira- have been so many and they have been so important that it is tory medicine. As shown in Figure 1, he was one of the first to difficult to pick and choose. Inevitably, there will be omissions; make sense out of the subdivisions of lung volume (1). He inevitably, some of us will not be pleased; and inevitably, one is measured pleural pressure in normal subjects (Figure 2), as well biased by one’s own experience. This will affect what I write, as in patients with congestive heart failure (Figure 3) and no matter how much I strive for objectivity. I apologize to any- emphysema, and showed that emphysema was characterized by one whose contributions I should have described but failed to loss of lung elastic recoil (2-4). Research in respiratory physi- do so. And to those whose work I do describe, I hope I have got ology and pathophysiology began in Canada. it right. Joe Doupe was a physiologist at the University of Manitoba, The focus of the present review is on the roots of respiratory Winnipeg, Manitoba. He was an original thinker and passed on physiological and pathophysiological research in Canada, and his ideas to medical students and residents. The influence he how this led to a contribution to the world literature far greater had on graduates of the University of Manitoba is legendary. than what one might predict from our small population. While Never, at least in Canada, has one man had such an extraordi- this legacy is still as strong today, only rarely do I refer to papers nary record in producing outstanding clinical investigators who published in the past 25 years. The seeds planted in the late became world-renowned in their field. Through these leaders, 1920s and early 1930s grew rapidly in the 1950s and came into Doupe has had an enormous impact on medicine in Canada. full bloom in the 1960s and 1970s. The present story is about Henry Friesen, John Dirks, the Hollenbergs, Arnold Naimark, this period, and it is a story about individuals and places, as Aubie Angel, Jim Hogg, Garth Bray and Barry Posner, to name much as it is about the vast amount of new knowledge that was a few, all owe a great deal to Joe Doupe. But this story is about created. Fortunately, the flowers are perennials and the garden Joe Doupe’s influence on Reuben Cherniack. Quite independ- is more beautiful than ever, but that is another story. ently of what was going on in Montreal, Reuben founded a hugely successful program in respiratory and intensive care The beginnings: Jonathon Meakins and Ronald Christie, medicine in Winnipeg. Here is what Arnold Naimark has to say along with Joe Doupe and Reuben Cherniack about Reuben: The roots of Canadian excellence in respiratory physiology and pathophysiology can be traced to two extraordinary men: They say that, for retail enterprises the three most impor- Jonathon Meakins and Ronald Christie. tant success factors are location, location, location. Well Dr Jonathon Meakins was recruited to McGill University for the development of excellence in respiratory disease (Montreal, Quebec) when, shortly after the First World War in Manitoba – the three most important success factors ended, Sir William Osler, then Regius Professor of Medicine at were Reuben, Reuben, Reuben. He was the sparkplug Oxford University (Oxford, England) and a graduate of McGill that inspired me and many of my contemporaries to pur- University, recommended that McGill University should hire a sue academic careers in respiratory medicine. He was our full-time Professor of Medicine. As a result, Dr Meakins arrived taskmaster, champion and friend. He was an instigator, in Montreal in 1924 as Canada’s first full-time Chairman of builder, developer and innovator – impatient with Medicine and Physician-in-Chief of the Royal Victoria Hospital. bureaucracy, generous in sharing credit for achievement His mandate was to establish research in his hospital department and with a keen eye for spotting and nurturing talent. as an essential part of academic medicine. Unfortunately, he did It doesn’t require many degrees of separation to trace not have any laboratory space. So, in what must have been an Reube’s influence in the careers of people engaged not exceptionally bloody battle, he wrested control of the clinical only in adult respiratory medicine but also in pediatrics biochemistry and hematology diagnostic laboratories from the (Chernick and Rigatto), in intensive care (Brian Kirk Department of Pathology, which provided his department with et al) in anesthesiology and in respiratory physiology – the necessary infrastructure to fulfill his mandate. both clinical and cellular (Naimark, Stephens, Kroeger, In 1927, he attracted Dr Ronald Christie to work with him Halayko). Add to this the folk he recruited (Younes, as a resident in medicine. Christie remained at the Royal Anthonisen, Mink, Kryger et al) and the trainees who Victoria Hospital for seven years. With Meakins, it was natural located and made their mark elsewhere… Meakins-Christie Laboratories, McGill University Health Centre Research Institute, Montreal, Quebec Correspondence: Dr Peter T Macklem, PO Box 250, Lansdowne, Ontario K0E 1L0. Telephone/fax 613-659-2001, e-mail [email protected] Can Respir J Vol 14 No 7 October 2007 ©2007 Pulsus Group Inc. All rights reserved 383 10427_macklem.qxd 02/10/2007 11:04 AM Page 384 Macklem L Case JP cm H2O +15 5 7:6:1933 Intrapleural pressure Complemental +10 air ++55 4 0 Vital capacity -5 3 Tidal Resting -10 Total air -15 capacity respiratory 2 Reserve level -20 air -25 Functional -30 residual air Residual 1 air Figure 1) The subdivisions of lung volume as described by Ronald Christie in 1932. Reproduced with permission from reference 1 A B cm H O cm H2O 2 Intrapleural pressure +5 +30 Case PD +0 +25 +20 Intrapleural 18:6:1933 -5 +15 -10 pressure +10 -15 +5 -20 +0 –5-5 –10 Sitting Lying Sitting Lying –15 –20 –25 500 –30 Tidal Vital cc air capacity Time marker 1 s 1000 cc 1000 Figure 3) Ronald Christie’s tracings of pleural pressure in a patient cc with congestive heart failure. Note that tidal pressure swings, closely in Tidal air Reserve phase with tidal volumes of approximately 360 mL, are approximately Complemental air air 30 cm H2O giving a dynamic compliance of only 0.012 L/cm H2O. To Time marker 5 s Time marker 5 s my knowledge, this is the first demonstration of stiff lungs in heart fail- ure. Reproduced with permission from reference 4 Figure 2) A Ronald Christie’s measurements of pleural pressure in a normal subject sitting upright and supine. B Pleural pressure in a normal subject during a deep inspiration to total lung capacity followed by a breath out to residual volume. Both figures are reproduced with permis- Physician-in-Chief of the Royal Victoria Hospital and sion from reference 2 Chairman of the Department of Medicine. I was a final year medical student at the time, and I well remember attending a Reube… brought together a fully integrated respira- professorial lecture that he gave shortly after his arrival. He tory medicine program embracing laboratories (both talked about lung compliance and resistance, and how the two clinical pulmonary function testing and experimental determined the work of breathing. He showed how, for a given labs for humans and animals), a respiratory critical care level of ventilation, these parameters changed with changes in unit and inhalation therapy service with links to clinical breathing frequency and tidal volume, and that there was a teaching units on the wards… I (still) attend chest particular ventilatory pattern that resulted in minimal work. rounds on a regular basis – and if nothing else they serve Minimal work in airways obstruction was shown to be a slow to remind me of how the lengthened shadow of Reube’s deep breathing pattern, whereas if the lungs were stiff, a rapid influence has extended through the decades. shallow breathing pattern was optimal (5). This lecture had a huge influence on me. Although it was still several years before Meakins and Christie in Montreal, and Doupe and I decided that respirology was my calling, there is no doubt Cherniack in Winnipeg, are the roots of Canadian excellence that Christie’s lecture played an important role in that decision. in respiratory physiology and pathophysiology. Christie brought David Bates with him to McGill University. When they arrived, there was already a strong Montreal respiratory medicine program in place, with Peter Pare in the After leaving Montreal, Christie took up an academic appoint- Department of Medicine, Bob Fraser in radiology and ment at St Bartholomew’s Hospital Medical School in Dag Munro in surgery. Soon Bates and Christie recruited London, England, and rose to the rank of Professor and many more doctors. Margot Becklake and Maurice McGregor Chairman. In 1955, he was recruited back to McGill came from South Africa. So did William ‘Whitey’ Thurlbeck University and, like Meakins before him, was appointed as via Harvard University (Boston, Massachusetts), who took 384 Can Respir J Vol 14 No 7 October 2007 10427_macklem.qxd 02/10/2007 11:04 AM Page 385 Canada’s contribution to respiratory physiology and pathophysiology Before 1000 600 After 500 800 400 600 300 (mL/min) 2 Respiratory Volume (cc) Volume O 400 200 V 100 200 Non respiratory 0 2 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 -22 -24 Intrathoracic pressure (cm H2O) 10 20 30 Figure 4) Reuben Cherniack’s dynamic pressure-volume loops meas- VE (L/min) ured before and after bronchodilators in a patient with emphysema and cor pulmonale.