Career perspective: Jerome A. Dempsey
© Dempsey; licensee BioMed Central Ltd. 2014
Received: 15 May 2014
Accepted: 18 June 2014
Published: 7 July 2014
I received most of my education in Canada, finishing at the University of Wisconsin (UW)-Madison medical school, where I have remained throughout my academic career. The research in our laboratory centered on the broad field of respiratory and cardiorespiratory physiology and pathophysiology as applied to exercise, sleep, hypoxia, and several chronic disease states. We used a team approach to our research with much emphasis given to the training of basic and clinical scientists in respiratory physiology and medicine. Our trainees provide the most important and lasting legacy to our laboratory's efforts.
Important contributions of our laboratory over about a 45-year period may be grouped into five problem areas, each one encompassing a series of 10 to 25 studies conducted over several years.
Hypoxic acclimatization research conducted in the mountains of Colorado and in hypobaric chambers provided evidence in several species which challenged a popular prevailing theory of the day to explain the role of brain fluid pH and chemoreceptor interactions in the regulation of breathing. These studies eventually led to the uncovering of a pivotal role for time-dependent sensitization of carotid chemoreceptors in hypoxia [2, 3]. This decade-long debate impressed on me the vital importance of questioning prevailing theories - even those that are teleologically attractive and apparently ‘entrenched’ - and also the key role played by carefully obtained ‘negative findings’ in moving forward a field of inquiry. These studies also introduced me to how exciting and fruitful teamwork could be. Outside mentoring from such superb scientists as Vladimir Fencil of Harvard was invaluable during this early period, and Tom Hornbein provided an exemplary model of integrity and humility in science.
The powerful role of CO2 chemosensitivity as a dominant regulator of breathing and breathing stability in sleep and as a key contributor to both central forms of apnea and even to the pathogenesis and treatment of obstructive sleep apnea [4, 5]. Our research using sleeping humans also led to mechanical ventilation studies which revealed a powerful role for nonchemical, mechanical influences on ventilatory control, i.e., so called neuro-mechanical inhibition and its strong inhibitory ‘after effects’ after the mechanical ventilation was withdrawn [6, 7]. Jim Skatrud and I introduced epidemiologists Terry Young and Mari Palta to the sleep and breathing field. This union of physiologists with population health scientists led to the birth of the Wisconsin Sleep Cohort (1988 to present) which, among other notable findings, was the first to report the prevalence of sleep disordered breathing in the general population  and also the consequences of sleep apnea to hypertension and mortality [9, 10].
Role of the ‘respiratory system’—gas exchange, airway mechanics, and respiratory muscle work and its cardiovascular interactions as significant contributors to O2 transport and exercise performance limitations in healthy endurance athletes as well as in COPD, chronic heart failure (CHF), and asthma [11, 12].
Contribution of cardiorespiratory interactions - both mechanical and reflex - in determining sympathetic vasoconstrictor outflow, stroke volume, and blood flow distribution during exercise in health and disease. A series of studies in animals and humans - both healthy and with CHF and COPD - established the importance of three types of reflex effects on sympathetic vasoconstriction during exercise, namely, (a) respiratory muscle metaboreflex, (b) carotid chemoreflex, and (c) type III to IV afferents from limb muscle [13, 14]. Through our overall aim of organ system integration - along with a large measure of serendipity - studies of these reflex effects also led to the still controversial hypothesis that locomotor muscle fatigue was a carefully regulated variable during exercise with afferent feedback from fatiguing muscle providing an important influence over central output to locomotor muscle, i.e., so-called central fatigue.
The use of chronically instrumented canines with separate perfusion of the isolated carotid chemoreflex provided evidence for (a) substantial contributions of carotid chemoreceptors to normal eupneic breathing, (b) stimulatory effects of global central nervous system hypoxia to ventilation, and (c) an interdependence of central chemoreceptor chemoresponsiveness to CO2 on the level of carotid chemoreceptor sensory input [15, 16].
What do I think are the important questions that need to be addressed currently and in the future? Certainly, the mechanisms and sites of action through which respiratory CO2 exchange (VCO2) modulates ventilation needs to resurface and to be pursued because it represents the ‘underpinning’ of the control of breathing. Sufficient research has been completed on synaptic plasticity within the respiratory control system to reveal its vital importance in health and disease—but the underlying mechanisms and their pathophysiologic significance deserve more emphasis.
Conceptually, it is crucial that molecular/genetic methods be combined with traditional physiologic approaches and that future ‘physiologists’ be trained in both approaches. Federal funding of basic medical science and its associated training in the US is in disarray!…without this, as a priority, we are on the brink of losing a generation (or more) of scientists.
Where did the research questions and experimental approaches we used originate? I would like to think that these were our original ideas, but realistically, I know that interactions with countless colleagues and students and the literature - including many grant applications of others - provided the impetus for many of these studies. This long list of influences includes those scientists with whom we have been engaged significant controversies such as John Severinghaus, Brian Whipp, Tom Hornbein, Fred Eldridge, and Magdy Younes. Controversy breeds progress!
Written informed consent was obtained from the participants for publication of the accompanying images in this manuscript. The consent form is held by the author and is available for review by the Editor-in-Chief.
aInventor of the Glasgow scale or Rankin scale in the 1950s for prognosis of stroke patients—still used today in population studies .
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