Book Review & Books Received

As originally published in The Physiologist
Volume 45, Number 4, August 2002, page 238

Books Received

Gravity and the Lung: Lessons from Microgravity
Lung Biology in Health and Disease, Vol. 160.
G. Kim Prisk, Manuel Paiva, and John B. West (Editors).
NY: Marcel Dekker, 2001, 383 pp., illus., index, $175.00.
ISBN: 0-8247-0570-X.

At this point, any book on real physiology is welcome, and here we have one on an interesting aspect of respiratory physiology. Volume 160 in the Lenfant series addresses questions about the effect of gravity on the respiratory system. The editors, Kim Prisk, Manuel Paiva, and John West were investigators in the Spacelab program, which ended in 1998. They designed many of the experiments that were done in orbit, and they analyzed and interpreted much of the data that were obtained. In addition, a number of studies of respiratory mechanics during parabolic flights have accrued over the last decade. This book draws on the information obtained from the Spacelab program and on centrifuge and parabolic flight studies. The objective of the authors is to use data obtained in hyper- and micro-G conditions to shed light on the effects of normal gravity on respiratory function. 

The book begins with an enjoyable review by West of the history of thought on the effects of gravity on respiration. He begins by tracing the history of ideas about the effect of gravity on the lung and chest wall, beginning with the work of Orth at the end of the 19th century and the work of Orsos, Wirz, and Rohrer in the first part of the 20th century. Then he gives a short history of the use of centrifuges and parabolic flight trajectories, and this leads to a section on the history of the USSR and US space programs. Readers of the Journal of Applied Physiology enjoyed a longer version of the section on the Soviet program that appeared in the October, 2001 issue of that Journal. In Chapter 2, Glaister reviews the work done in a centrifuge at Farnborough in the 1960’s and 1970’s. 

In Chapter 3, Estenne provides a well-organized and clearly-written review of the effect of gravity on the chest wall. He notes that on board the Spacelab, FRC was observed to be 15% lower than the preflight standing value. This observation is consistent with observations during parabolic flights, and he concludes that the net effect of gravity in the standing position is inspiratory. It seems strange that at this date we have no solidly established value of the gravitational force on the rib cage. Two noteworthy papers on this subject have appeared since the chapter was written. One, by Loring, et al. (J Appl Physiol 90: 2141-2150, 2001), gives the best estimate of this force near FRC, and the other, by Bettinelli, et al. (J Appl Physiol 92: 709-716, 2002), indicates that the gravitational forces on the chest wall depend strongly on lung volume.

Paiva and Prisk, in Chapter 4, and Prisk, in Chapter 6, describe data on ventilation and perfusion inhomogeneities, respectively. Both chapters begin with brief reviews of classical ideas about the effects of gravity. The chapter on ventilation focuses on the slope of phase III during multi-breath washin maneuvers and ignores data on concentration vs. breath number. The interpretation of these data yield qualitative information about the mechanisms that contribute to nonuniform ventilation, but no quantitative estimate of the magnitude of ventilation inhomogeneity. Tests of perfusion inhomogeneity in hyper- and micro-G conditions are limited to measurements of the amplitude of cardiogenic oscillations in CO2 concentration in expired gas after breathhold. Both ventilation and perfusion inhomogeneities are reduced under micro-G conditions, but not by much. Twenty years ago, this would have been a surprising result, but in light of the data on nongravitational inhomogeneities that have appeared over the last decade, this result is confirmational. Non-gravitational inhomogeneity of perfusion is given its due in Chapter 7 by Hlastala, Robertson, and Glenny.

In Chapter 10, Buckey describes the effect of gravity on central venous pressure (CVP). CVP had been expected to be higher in micro-G because of an expected shift of fluid to the thorax. In fact, CVP was found to be lower in micro-G. Buckey discusses possible explanations for this result, and this discussion raises a number of interesting questions about the determinants of intrathoracic and blood pressures. Another aspect of this question is discussed in a chapter on control of ventilation by Prisk. He notes that the difference between the response of ventilation to hypoxia in micro-G and standing1-G is similar to the difference between supine 1-G and standing 1-G, and he suggests that both are due to differences in blood pressure at the carotid bodies.
The book also includes chapters on the effects of gravity on aerosol transport, gas exchange, exercise and gas exchange, fluid balance in the lung, and decompression sickness. The broad range of topics that are covered in the book illustrates the fact that gravity and hence, posture, play a role in many aspects of respiratory physiology. 

Theodore A. Wilson
Minneapolis, Minnesota

Corrigenda: A Book Review of The Autonomic Nervous System in Health and Disease was published in the June 2002 , Vol. 45 (3) issue of The Physiologist without the reviewer’s name. The reviewer was J.A. Armour, Dalhousie University. The Physiologist regrets this error. 

The Autonomic Nervous System in Health and Disease
David S. Goldstein
Monticello, NY: Marcel Dekker, Inc., 2001, 618 pp., illus., index, $195.00. 
ISBN: 0-8247-0408-8.

To the Editor:

I am writing about the review of my book, The Autonomic Nervous System in Health and Disease.(1)” The review appeared without by-line in Volume 45 No. 3, pp. 164-165, of The Physiologist. My thanks to you for publishing the review, and to the Reviewer for the time and effort spent writing it. I also thank the Reviewer for several complimentary comments, but I do wish to respond to some criticisms.

As noted correctly by the Reviewer, the book strives to convey concepts to a general audience, especially to clinical researchers and practitioners in the nascent discipline of neurocardiology. Most of the literature about central interactions regulating sympathetic and parasympathetic nervous system outflows, and about central neural interactions underlying responses to stresses, has consisted of studies in anesthetized animals. Few organizing concepts have emerged from a plethora of phenomenological data, and one may reasonably question the relevance of such studies to issues of human health and disease. For instance, the Reviewer dislikes the concept of splinting of baroreceptors in arterial walls as a cause of baroreflex inactivation. The literature in animals emphasizes much more plastic adjustments in baroreflex function, and the discussion in the book could well have presented this mass of experimental information in a more balanced way. Nevertheless, from the point of view of a clinical neurocardiologist, I would guess that chronic atherosclerotic changes do indeed have an important impact on baroreflex regulation of blood pressure. Studies as long ago as the 1960’s described circulatory effects of encased carotid sinuses and success of “baropacing” for chronic clinical hypertension (9).

Analogously, although animal studies support the assertion that angiotensin II exerts “cardioaugmenter” effects by modifying populations of intrinsic cardiac neurons, I am unaware of clinical research support for such an effect of angiotensin II-or, for that matter, for the existence of functionally important intrinsic cardiac neurons in humans. On the contrary, the bradycardic effect of systemically administered angiotensin II in conscious humans provided the basis for the original description, by Smyth, Sleight, and Pickering in 1969, of their well accepted clinical method of measuring baroreflex-cardiovagal gain, by injection of vasoactive drugs with little or no direct acute effects on heart rate (14).

The concept proposed in the book that the sympathetic nervous and adrenomedullary hormonal systems play different roles in the body economy conflicts with that of a unitary “sympathoadrenal system,” promulgated by Cannon in the early 20th century and still widely accepted. The Reviewer seems to view the notion of different functions, labeled for didactic convenience as “housekeeping” and “distress,” as without scientific foundation. The text goes into some detail, however, in citing and analyzing the relevant literature. For instance, psychologically distressing situations preferentially increase adreno-medullary secretion, as indicated by plasma epinephrine levels, whereas adjustments to challenges to homeostasis such as to orthostasis, meal ingestion, exposure to decreased environmental temperature, and mild exercise preferentially increase sympathetic neural outflows, as indicated by plasma norepinephrine levels. (2) Conversely, sedation preferentially attenuates adrenomedullary responses to real-life distressing situations in humans, a finding reported by our group more than 15 years ago (3) and replicated several times since then. One may of course argue about the appropriateness of the labels used for the distinctive roles of these two limbs of the autonomic nervous system, but clearly there is scientific foundation for the concept of differential regulation of the adrenomedullary hormonal and sympathetic nervous systems in humans.

The Reviewer argues that epinephrine exerts significant effects on total vascular resistance but not by decreasing arteriolar resistance. This seemingly paradoxical statement does not fit with the clinical research literature. Studies using intra-arterial infusion of epinephrine have shown that in humans, epinephrine markedly and unequivocally decreases forearm vascular resistance, (8) and relatively small increments in circulating epinephrine levels are associated with decreased total peripheral resistance (7).

Concerning autonomic regulation of gastrointestinal function, the text reflects accurately the poor current fund of knowledge about components of the autonomic nervous system that actually regulate gastrointestinal function and how they are coordinated. The presentation does not negate in any way the potential importance of this contribution. An example of such deficiency in knowledge is the source of dopamine produced in the gastrointestinal tract. In humans, most of dopamine production and metabolism take place not in the brain, not in the sympathetic nervous system, and not in the adrenal medulla, but in mesenteric organs. (4) Surely locally produced dopamine must play a role in autonomic regulation of gastrointestinal function, but this role remains largely mysterious.

The Reviewer objects to concepts that would distinguish “goals” of low-pressure and high-pressure baroreceptor systems. Researchers have disagreed about this for many years, and the discussion notes the difficulty of the problem, especially as applied to human health and disease. The presentation does not justify the severe and inappropriate accusation of “misinformation.”

Regarding catecholamine production in the heart, animal literature about ventricular interstitial catecholamine content does not put into doubt—and if anything confirms—the validity of clinical findings based on tracer kinetic approaches for assessing cardiac presynaptic sympathetic function, using local rates of entry of norepinephrine, dihydroxyphenylglycol, and dihydroxyphenylalanine into the venous drainage. The important modification by Kopin and co-workers in 1998 (11) bears particular mention in this regard.

As an example of “varied and sometimes fanciful conclusions,” the Reviewer cites the statement that coronary artery occlusion is less likely to lead to ventricular fibrillation if psychological distress is minimized, presumably because an extensive enough infarct would precipitate ventricular fibrillation anyway. Studies by Verrier, Lown, and others, however, provide substantial evidence in support of a role of acute emotional distress in lowering the threshold for ventricular fibrillation (13). The text does draw inferences here from studies of coronary occlusion in animals, (1, 10, 12) but an abundance of indirect clinical literature would be consistent with those inferences, as discussed in the text.

Finally, the Reviewer argues that the text overdraws contrasts between reductionism and homeostatic thinking, since understanding neurocardiologic syndromes requires both approaches. I share the hope and expectation that the future of medical science will see the merging of these perspectives. This is the essence of what I call “scientific integrative medicine” (5). Perhaps the text should have focused more on the need for “synthesis” rather than the present dialectic.

In summary, in critiquing this book the Reviewer seems to have drawn heavily from a wealth of animal literature and, in so doing, failed to consider adequately the main stated purposes of the book, which are to present principles of neurocardiology, teach integrative physiology, foster testing of mechanistic and experimental therapeutic hypotheses, help understand neurocardiologic disorders, and improve the management of patients with dysautonomias. Time will tell whether the book moves the field forward toward these goals. 

David S. Goldstein

References 

1. DeSilva RA, Verrier RL, Lown B. The effects of psychological stress and vagal stimulation with morphine on vulnerability to ventricular fibrillation (VF) in the conscious dog. Am Heart J 1978;95:197-203.
2. Dimsdale JE, Moss J. Plasma catecholamines in stress and exercise. JAMA 1980;243:340-342.
3. Dionne RA, Goldstein DS, Wirdzek PR. Effects of diazepam premedication and epinephrine-containing local anesthetic on cardiovascular and plasma catecholamine responses to oral surgery. Anesth Analg. 1984;63:640-646.
4. Eisenhofer G, Aneman A, Friberg P, Hooper D, Fandriks L, Lonroth H, et al. Substantial production of dopamine in the human gastrointestinal tract. J Clin Endocrinol Metab 1998;42:374-377.
5. Goldstein DS. On the dialectic between molecular genetics and integrative physiology: Toward a new medical science. Perspectives Biol Med 1997;40:505-515.
6. Goldstein DS. The Autonomic Nervous System in Health and Disease. New York, NY: Marcel Dekker, Inc.; 2001.
7. Goldstein DS, Dionne R, Sweet J, Gracely R, Brewer HB, Jr., Gregg R, et al. Circulatory, plasma catecholamine, cortisol, lipid, and psychological responses to a real-life stress (third molar extractions): effects of diazepam sedation and of inclusion of epinephrine with the local anesthetic. Psychosom Med 1982;44:259-272.
8. Grossman E, Chang PC, Hoffman A, Tamrat M, Goldstein DS. Evidence for functional a2-adrenoceptors on vascular sympathetic nerve endings in the human forearm. Circ Res 1991;69:887-897.
9. Kezdi P, editor. Baroreceptors and Hypertension. Oxford, UK: Pergamon; 1967.
10. Kolman BS, Verrier RL, Lown B. Effect of vagus nerve stimulation upon excitability of the canine ventricle. Am J Cardiol 1976;37:1041-1045.
11. Kopin IJ, Rundqvist B, Friberg P, Lenders J, Goldstein DS, Eisenhofer G. Different relationships of spillover to release of norepinephrine in human heart, kidneys, and forearm. Am J Physiol 1998;275:R165-R173.
12. Lombardi F, Verrier RL, Lown B. Relationship between sympathetic neural activity, coronary dynamics and vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion. Am Heart J 1983; 105:958-965.
13. Lown B, Verrier RL. Neural activity and ventricular fibrillation. N Engl J Med 1976;294:1165-1170.
14. Smyth HS, Sleight P, Pickering GW. Reflex regulation of arterial pressure during sleep in man: quantitative method of assessing baroreflex sensitivity. Circ Res 1969;24:109-121.

Books Received

Blaustein’s Pathology of the Female Genital Tract, 5th Edition.
Robert J. Kurman, (Editor).
New York: Springer-Verlag, 2002, 1391 pp., illus., index, $189.00.
ISBN: 0-387-95203-9. 

Exercise and Stress Response: The Role of Stress Proteins.
Marius Locke and Earl G. Noble (Editors).
CRC Series in Exercise Physiology.
Boca Raton, FL: CRC, 2002, 226 pp., illus., index, $99.95.
ISBN: 0-8493-0458-X.

In Vivo Optical Imaging of Brain Function.
Ron D. Frostig (Editor).
Methods & New Frontiers in Neuroscience
Boca Raton, FL: CRC, 2002, 259 pp., illus., index, $119.95.
ISBN: 0-8493-2389-4.

Perceptual Learning.
Manfred Fahle and Tomaso Poggio (Editors).
Cambridge, MA: MIT Press, 2002, 455 pp., illus., index, $65.00.
ISBN: 0-262-06221-6.

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