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EDITORIAL FOCUS
ESSAYS ON APS CLASSIC PAPERS
Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536
ABSTRACT
This essay looks at the historical significance of three APS classic papers that are freely available online:
Cannon WB and de la Paz D. Emotional stimulation of adrenal secretion. Am J Physiol 28: 64-70, 1911 (http://ajplegacy.physiology.org/cgi/reprint/28/1/64).
Cannon WB. The emergency function of the adrenal medulla in pain and the major emotions. Am J Physiol 33: 356-372, 1914 (http://ajplegacy.physiology.org/cgi/reprint/33/2/356).
Cannon WB. Studies on the conditions of activity in endocrine glands. V. The isolated heart as an indicator of adrenal secretion induced by pain, asphyxia and excitement. Am J Physiol 50: 399-432, 1919 (http://ajplegacy.physiology.org/cgi/reprint/50/3/399).
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Cannon and his colleagues followed the 1911 report with other studies of the physiological effects of adrenal secretions. By 1914, he and others had reported that injection of "the substance produced by the adrenal medulla (adrenin, adrenalin, epinephrine, etc.) is capable of producing many profound bodily changes...: a cessation of the activities of the alimentary canal; a notable shifting of the circulation from the great vessels of the abdomen to the lungs, heart, limbs and central nervous system; an increased cardiac vigor; and an augmentation of the sugar content of the blood" (2). He then championed the view that "...the absolutely essential organs—the 'tripod of life'—the heart, lungs and brain (as well as the skeletal muscles)—are, in times of excitement, when the adrenal glands discharge, abundantly supplied with blood taken from organs of less importance in critical moments" (2). But Cannon's views were rigorously challenged by other investigators. In particular, his conclusion that adrenal secretion increased in response to emotional excitement was contested (11), and, at an even more fundamental level, Gley and Quinquaud (8) contended that adrenin was not secreted in sufficient amount to be carried effectively to organs on which it could act. Contemporary physiologists would quickly reject these arguments, but the issues were confused at that time. In fact, then as now, challenges by one scientist of another's observations stimulated additional experiments, and in 1920, Cannon described new experiments in the third (4) of these now classic papers to respond to criticisms of his earlier work and to bolster his previous conclusions.
Cannon's 1920 paper begins with a thorough review of previously published evidence for and against adrenal secretion in response to pain, asphyxia, and emotional excitement. One of the more compelling potential difficulties with earlier work, including the 1911 demonstration, is that the effects of adrenin were tested in blood that had been removed from the body. Cannon's solution was to use the denervated heart, which he noted is "highly sensitive to adrenin" (4), to circumvent the objections leveled at earlier studies. He acknowledged that this solution was triggered by earlier "incidental observations" of other investigators; no scientist, not even a Dr. Cannon, works in a vacuum. He stated that the approach is particularly advantageous because "the method permits a graphic record from which may be judged the latent period and the duration of secretion of the adrenal glands in consequence of stimulation" (4). He explains that the decentralized feline heart "... is thus wholly disconnected from the central nervous system and any agency causing an increase in the heart rate must exert its influence through the bloodstream" (4). He then illustrates a tachycardia in the animal when excited compared with the calm state; removing the adrenals in some animals eliminated the response, although some heart rate speeding persisted in other subjects. Although there are certainly limitations to Cannon's experimental approach, his conclusions still stand today. Moreover, the development of heart transplantation renewed interest in the regulation of the denervated heart, and, about 50 years after Cannon's publication, the present author and his colleagues (10) surgically denervated the primate heart and described quantitatively the latency and amplitude of the cardiac chronotropic and inotropic increases during a tone followed by shock; no significant augmentations occurred during a tone followed by food. We cited Cannon's 1920 paper to substantiate the importance of the adrenal contribution to the "fear response" and also noted a later publication where he described the phenomenon of "denervation supersensitivity" (7).
One additional observation regarding the 1920 paper may be worthwhile with respect to the timeless workings of science: in a concluding section of his paper, Cannon examined two theories that were then current "to account for the role played by the adrenal medulla in the bodily economy" (4). One of these, which he described and then rejected in favor of his "emergency theory," holds that "the function of the secreted adrenin is to maintain the sympathetic endings in a state of responsiveness to nervous stimulation or in a condition of moderate activity or tone" (4). While Cannon's contention that "it is the sympathetic division of the autonomic system which is the primary agency in mobilizing the bodily forces in times of great fear or rage" (Ref. 3; Cannon's italics) has stood the test of time, many experiments have also established that other secretions of the adrenal gland, most particularly cortisol, are absolutely essential for maintaining vascular smooth muscle responsiveness to adrenergic stimulation and thereby in the maintenance of on-going vasomotor tone. In this regard, perhaps it is fair to say that no avenue of scientific exploration ever leads to a total dead end.
It often happens that the splendor of a conceptually inspiring peak in our understanding of physiological function transiently obscures our appreciation of other important phenomena. In fact, "Mount Homeostasis," which emphasizes the maintenance of a stable internal environment, appears to have a sister peak, "Mount Variability," which emphasizes the value of an analysis of the dynamic nature of cardiovascular "signals" such as blood pressure (e.g., the precise manner in which blood pressure fluctuates around its "steady state" value). Today large portions of Mount Variability are still enshrouded in mist, much as Mount Homeostasis was in the early 20th century. There is, however, every promise that this new landmark will eventually be as prominent as its magnificent sister.
Walter Cannon's son, Dr. Bradford Cannon, reports (http://www.harvardsquarelibrary.org/unitarians/cannon_walter.html) that his father and mother, on their honeymoon, were the first to reach the summit of an unclimbed peak in what is now Glacier National Park at the head of Lake McDonald. The United States Geological Survey subsequently named it Mount Cannon (48.63330 lat., –113.75123 long.). Dr. Cannon's other "mountains" continue to serve as landmarks in our understanding of body function.
FOOTNOTES
Address for correspondence: D. C. Randall, Dept. of Physiology, Univ. of Kentucky, Lexington, KY 40506-0298 (E-mail:randall{at}uky.edu)
1 The present author still has the recording he made as a first-year graduate student of intestinal muscle contractions using the "smoked kymograph." Moreover, until relatively recently (i.e., when teaching laboratories were largely discontinued), he used this preparation and a polygraph recorder to demonstrate the effects of epinephrine and acetylcholine on smooth muscle motility to undergraduate, medical, and graduate students. 
REFERENCES
This article has been cited by other articles:
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  P. P. Bertrand and R. L. Bertrand Teaching basic gastrointestinal physiology using classic papers by Dr. Walter B. Cannon Advan Physiol Educ, June 1, 2007; 31(2): 136 - 139. [Abstract] [Full Text] [PDF]
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