Point: the lactate paradox does/does not occur during exercise at high altitude.
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Biomedical subjects
Publications and source records attributed to John B West.
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The lungs of domestic chickens were perfused with blood or dextran/saline and the pulmonary artery pressure (P(a)) and venous pressure (P(v)) were varied in relation to air capillary pressure (P(A)). In Zone 3 conditions, pulmonary vascular resistance (PVR) was virtually unchanged with increases in either P(a) or P(v). This is very different behavior from mammals where the same interventions greatly reduce PVR. In Zone 2 conditions blood flow was essentially independent of P(v) as in mammalian lungs but all the capillaries appeared to be open, apparently incompatible with a Starling resistor mechanism. In Zone 1 the capillaries were open even when P(A) exceeded P(a) by over 30 cm H(2)O which is very different behavior from that of the mammalian lung. We conclude that the air capillaries that surround the blood capillaries provide rigid support in both compression and expansion of the vessels. The work suggests a pathogenesis for pulmonary hypertension syndrome in chickens which costs the broiler industry $1 billion per year.
The gas exchanging region in the avian lung, although proportionally smaller than that of the mammalian lung, efficiently manages respiration to meet the high energetic requirements of flapping flight. Gas exchange in the bird lung is enhanced, in part, by an extremely thin blood-gas barrier (BGB). We measured the arithmetic mean thickness of the different components (endothelium, interstitium, and epithelium) of the BGB in the domestic chicken lung and compared the results with three mammals. Morphometric analysis showed that the total BGB of the chicken lung was significantly thinner than that of the rabbit, dog, and horse (54, 66, and 70% thinner, respectively) and that all layers of the BGB were significantly thinner in the chicken compared with the mammals. The interstitial layer was strikingly thin in the chicken lung ( approximately 86% thinner than the dog and horse, and 75% thinner than rabbit) which is a paradox because the strength of the BGB is believed to come from the interstitium. In addition, the thickness of the interstitium was remarkably uniform, unlike the mammalian interstitium. The uniformity of the interstitial layer in the chicken is attributable to a lack of the supportive type I collagen cable that is found in mammalian alveolar lungs. We propose that the surrounding air capillaries provide additional structural support for the pulmonary capillaries in the bird lung, thus allowing the barrier to be both very thin and extremely uniform. The net result is to improve gas exchanging efficiency.
Extended exposure to microgravity (microG) is known to reduce strength in weight-bearing muscles and was also reported to reduce respiratory muscle strength. Short- duration exposure to microG reduces vital capacity (VC), a surrogate measure for respiratory muscle strength, for the first few days, with little change in O2 uptake, ventilation, or end-tidal partial pressures. Accordingly we measured VC, maximum inspiratory and expiratory pressures, and indexes of pulmonary gas exchange in 10 normal subjects (9 men, 1 woman, 39-52 yr) who lived on the International Space Station for 130-196 days in a normoxic, normobaric atmosphere. Subjects were studied four times in the standing and supine postures preflight at sea level at 1 G, approximately monthly in microG, and multiple times postflight. VC in microG was essentially unchanged compared with preflight standing [5.28 +/- 0.08 liters (mean +/- SE), n = 187; 5.24 +/- 0.09, n = 117, respectively; P = 0.03] and considerably greater than that measured supine in 1G (4.96 +/- 0.10, n = 114, P < 0.001). There was a trend for VC to decrease after the first 2 mo of microG, but there were no changes postflight. Maximum respiratory pressures in microG were generally intermediate to those standing and supine in 1G, and importantly they showed no decrease with time spent in microG. O2 uptake and CO2 production were reduced (approximately 12%) in extended microG, but inhomogeneity in the lung was not different compared with short-duration exposure to microG. The results show that VC is essentially unchanged and respiratory muscle strength is maintained during extended exposure to microG, and metabolic rate is reduced.
BACKGROUND: Climbers on the summit of Mt. Everest are exposed to extreme hypoxia, and the physiological implications are of great interest. Inferences have been made from alveolar gas samples collected on the summit, but arterial blood samples would give critical information. We propose a plan to insert an arterial catheter at an altitude of 8000 m, take blood samples above this using an automatic sampler, store the samples in glass syringes in an ice-water slurry, and analyze them lower on the mountain 4 to 6 hours later. RESULTS: A preliminary design of the automatic sampler was successfully tested at the White Mountain Research Station (altitude 3800 m-4300 m). To determine how much the blood gases changed over a long period, rabbit blood was tonometered to give a gas composition close to that expected on the summit (PO2 4.0 kPa (30 mmHg), PCO2 1.3 kPa (10 mmHg), pH 7.7) and the blood gases were measured every 2 hours for 8 hours both at sea level and 3800 m. The mean changes were PO2 +0.3 to +0.4 kPa (+2 to +3 mmHg), PCO2 0 to +0.13 kPa (+1 mmHg), pH -0.02 to +0.04, base excess -0.7 to +1.2 mM. In practice the delay before analysis should not exceed 4 to 6 hours. The small paradoxical rise in PO2 is presumably caused mainly by contamination of the blood with air. CONCLUSION: We conclude that automatic arterial blood sampling at high altitude is technically feasible and that the changes in the blood gases over a period of several hours are acceptably small.
Flying requires enormous energy and some birds have higher mass-specific maximal oxygen consumptions than any mammal. The bird lung is very efficient partly because of an extremely thin blood-gas barrier so that some birds have thinner barriers than any mammals. We show here that in addition to the total barrier being very thin, the interstitium which is responsible for the barrier's strength is extraordinarily thin. This observation is paradoxical because intense exercise raises the pressure in pulmonary capillaries and results in large stresses in the capillary walls thus predisposing them to structural failure. For example, all galloping racehorses break their pulmonary capillaries. We propose that the explanation for how the bird can be so highly energetic yet also have such apparently fragile capillaries is the mechanical support provided by the dense packing of rigid air capillaries around the blood capillaries in the gas exchanging region of the lung. This architecture is very different from that in the mammalian lung.
I have probably had more fun doing high-altitude physiology than most people. Some 45 years ago I applied to be a member of Sir Edmund Hillary's Silver Hut expedition and was accepted in spite of having no previous climbing experience. On this project a group of physiologists wintered at an altitude of 5800 m just south of Everest and carried out an extensive research program. Subsequently measurements were extended up to an altitude of 7440 m on Makalu. In fact the altitude of these field measurements of VO(2max) has never been exceeded. This led to a long interest in high-altitude medicine and physiology which culminated in the 1981 American Medical Research Expedition to Everest during which 5 people reached the summit and the first physiological measurements on the summit were made. Among the extraordinary findings were an extremely low alveolar PCO2 of 7-8 mmHg, an arterial pH (from the measured PCO2 and blood base excess) of over 7.7, and a VO(2max) of just over one liter/min. More recently a major interest has been the pathogenesis of high altitude pulmonary edema which we believe is caused by damage to pulmonary capillaries when the pressure inside some of them increases as a result of uneven hypoxic pulmonary vasoconstriction ("stress failure"). Another interest is improving the conditions of people who need to work at high altitude by oxygen enrichment of room air. This enhances well-being and productivity, and is now being used or planned for several high-altitude telescopes up to altitudes of 5600 m. Other recent high-altitude projects include establishing an international archive on high-altitude medicine and physiology at UCSD, several books in the area including the historical study High Life, and editing the journal High Altitude Medicine & Biology.
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Georges Dreyer was the first Professor of Pathology at Oxford University and he held this post from 1907 to 1934. Although his main research interests were in bacteriology and immunity, he made important contributions to respiratory physiology, but these have been almost completely forgotten. He developed a new apparatus for administering low oxygen mixtures to test the effects of hypoxia in airmen during World War I, developed a high successful oxygen delivery system, was responsible for the first low-pressure chamber in a UK academic institution, and carried out some physiological measurements in the chamber that were years ahead of their time. His chamber was also used by a group from Cambridge and Turin, Italy for a series of important physiological studies. In spite of these contributions, almost nobody who works in respiratory physiology today, even in Oxford, recognizes the name of Dreyer.
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Extravehicular activity (EVA) during spaceflight involves a significant decompression stress. Previous studies have shown an increase in the inhomogeneity of ventilation-perfusion ratio (VA/Q) after some underwater dives, presumably through the embolic effects of venous gas microemboli in the lung. Ground-based chamber studies simulating EVA have shown that venous gas microemboli occur in a large percentage of the subjects undergoing decompression, despite the use of prebreathe protocols to reduce dissolved N(2) in the tissues. We studied eight crewmembers (7 male, 1 female) of the International Space Station who performed 15 EVAs (initial cabin pressure 748 mmHg, final suit pressure either approximately 295 or approximately 220 mmHg depending on the suit used) and who followed the denitrogenation procedures approved for EVA from the International Space Station. The intrabreath VA/Q slope was calculated from the alveolar Po(2) and Pco(2) in a prolonged exhalation maneuver on the day after EVA and compared with measurements made in microgravity on days well separated from the EVA. There were no significant changes in intrabreath VA/Q slope as a result of EVA, although there was a slight increase in metabolic rate and ventilation (approximately 9%) on the day after EVA. Vital capacity and other measures of pulmonary function were largely unaltered by EVA. Because measurements could only be performed on the day after EVA because of logistical constraints, we were unable to determine an acute effect of EVA on VA/Q inequality. The results suggest that current denitrogenation protocols do not result in any major lasting alteration to gas exchange in the lung.
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The 1952 Copenhagen poliomyelitis epidemic provided extraordinary challenges in applied physiology. Over 300 patients developed respiratory paralysis within a few weeks, and the ventilator facilities at the infectious disease hospital were completely overwhelmed. The heroic solution was to call upon 200 medical students to provide round-the-clock manual ventilation using a rubber bag attached to a tracheostomy tube. Some patients were ventilated in this way for several weeks. A second challenge was to understand the gas exchange and acid-base status of these patients. At the onset of the epidemic, the only measurement routinely available in the hospital was the carbon dioxide concentration in the blood, and the high values were initially misinterpreted as a mysterious "alkalosis." However, pH measurements were quickly instituted, the Pco(2) was shown to be high, and modern clinical respiratory acid-base physiology was born. Taking a broader view, the problems highlighted by the epidemic underscored the gap between recent advances made by physiologists and their application to the clinical environment. However, the 1950s ushered in a renaissance in clinical respiratory physiology. In 1950 the coverage of respiratory physiology in textbooks was often woefully inadequate, but the decade saw major advances in topics such as mechanics and gas exchange. An important development was the translation of the new knowledge from departments of physiology to the clinical setting. In many respects, this period was therefore the beginning of modern clinical respiratory physiology.
In 1660, Robert Boyle (1627-1691) published his landmark book New Experiments Physico-Mechanicall, Touching the Spring of the Air, and its Effects... in which he described the first controlled experiments of the effects of reducing the pressure of the air. Critical to this work was the development of an air pump by Boyle with Robert Hooke (1635-1703). For the first time, it was possible to observe physical and physiological processes at both normal and reduced barometric pressures. The air pump was described in detail, although the exact design of the critical piston is unclear. Boyle reported 43 separate experiments, which can conveniently be divided into 7 groups. The first experiments were on the "spring of the air," that is the pressure developed by the air when its volume was changed. Several experiments described the behavior of the barometer invented by Torricelli just 16 years before when it was introduced into the low-pressure chamber. The behavior of burning candles was discussed, although this emphasized early misunderstandings of the nature of combustion. There were some physiological observations, although these were later extended by Boyle and Hooke. The effects of the low pressure on such diverse physical phenomena as magnetism, sound propagation, behavior of a pendulum, evolution of gases from liquids, and the behavior of smoke were described. This classic book is brimming with enthusiasm and fresh ideas even for today and deserves to be better known.
In gas exchangers, the tissue barrier, the partition that separates the respiratory media (water/air and hemolymph/blood), is exceptional for its remarkable thinness, striking strength, and vast surface area. These properties formed to meet conflicting roles: thinness was essential for efficient flux of oxygen by passive diffusion, and strength was crucial for maintaining structural integrity. What we have designated as "three-ply" or "laminated tripartite" architecture of the barrier appeared very early in the evolution of the vertebrate gas exchanger. The design is conspicuous in the water-blood barrier of the fish gills through the lungs of air-breathing vertebrates, where the plan first appeared in lungfishes (Dipnoi) some 400 million years ago. The similarity of the structural design of the barrier in respiratory organs of animals that remarkably differ phylogenetically, behaviorally, and ecologically shows that the construction has been highly conserved both vertically and horizontally, i.e., along and across the evolutionary continuum. It is conceivable that the blueprint may have been the only practical construction that could simultaneously grant satisfactory strength and promote gas exchange. In view of the very narrow allometric range of the thickness of the blood-gas barrier in the lungs of different-sized vertebrate groups, the measurement has seemingly been optimized. There is convincing, though indirect, evidence that the extracellular matrix and particularly the type IV collagen in the lamina densa of the basement membrane is the main stress-bearing component of the blood-gas barrier. Under extreme conditions of operation and in some disease states, the barrier fails with serious consequences. The lamina densa which in many parts of the blood-gas barrier is <50 nm thin is a lifeline in the true sense of the word.