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Biomedical subjects

E R Weibel

Publications and source records attributed to E R Weibel.

At least 19 recordsLinked to original sources
PubMed2004

An optimal bronchial tree may be dangerous.

The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling and can ensure minimal dissipation. The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure. Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.

Asthma↗
PubMed2002

Smaller is better--but not too small: a physical scale for the design of the mammalian pulmonary acinus.

The transfer of oxygen from air to blood in the lung involves three processes: ventilation through the airways, diffusion of oxygen in the air phase to the alveolar surface, and finally diffusion through tissue into the capillary blood. The latter two steps occur in the acinus, where the alveolar gas-exchange surface is arranged along the last few generations of airway branching. For the acinus to work efficiently, oxygen must reach the last branches of acinar airways, even though some of it is absorbed along the way. This "screening effect" is governed by the relative values of physical factors like diffusivity and permeability as well as size and design of the acinus. Physics predicts that efficient acini should be space-filling surfaces and should not be too large. It is shown that the mammalian acini fulfill these requirements, small mammals being more efficient than large ones both at rest and in exercise.

Animals↗
PubMed2001

Preventing mediastinal shift after pneumonectomy impairs regenerative alveolar tissue growth.

To examine the effects of mechanical lung strain on regenerative growth of alveolar septal tissue after pneumonectomy (PNX), we replaced the right lungs of adult dogs with a custom-shaped inflatable silicone prosthesis. The prosthesis was either inflated (Inf) to maintain the mediastinum at the midline or deflated to allow mediastinal shift. The animals were euthanized approximately 15 mo later, and the lungs were fixed at a constant distending pressure. With the Inf prostheses, lung expansion, alveolar septal tissue volumes, surface areas, and diffusing capacity of the tissue-plasma barrier were significantly lower than with the deflated prostheses; the expected post-PNX tissue responses were impaired by 30-60%. Capillary blood volume was significantly higher with Inf prostheses, consistent with microvascular congestion. Measurements in the Inf group remained consistently and significantly higher than those expected for a normal left lung, indicating persistence of partial compensation. In one dog, delayed deflation of the prosthesis 9-10 mo after PNX led to vigorous lung expansion and septal tissue growth, particularly of type II epithelial cells. We conclude that mechanical lung strain is a major signal for regenerative lung growth; however, other signals are also implicated, accounting for a significant fraction of the compensatory response to PNX.

Animals↗
PubMed2000

Structural and functional limits for oxygen supply to muscle.

Environmental oxygen is transported by the respiratory cascade to the site of oxidation in active tissues. Under conditions of heavy exercise it is ultimately the working skeletal muscle cells that determine the aerobic demand as over 90% of energy is spent in muscle cells. Oxygen is transported in the circulation bound to haemoglobin of erythrocytes while substrates are transported in the plasma. The supply of oxygen must be continuous because there are only minimal oxygen stores in the body of most mammalian species while substrates are stored in significant quantities both within muscle cells as also in organismic substrate stores. The pathways for oxygen and substrates ultimately converge in muscle mitochondria. In mammals, a structural limitation of carbohydrate and lipid transfer from the microvascular system to muscle cells is reached at a moderate work intensity (i.e. at less than 50% of VO2max). At higher work rates intracellular substrate stores must be used for oxidation. It is therefore not surprising to find larger intramyocellular carbohydrate and lipid stores in 'athletic' species as well as in endurance-trained human athletes. The transfer limitations for carbohydrates and lipids presumably occur on the level of the sarcolemma. These findings imply that the design of the respiratory cascade from lungs to muscle mitochondria has to be analysed with regard to satisfying the demand for oxygen of the working muscle cells. Substrate stores are replenished at low flux rates during periods of rest and are stored intracellularly. They are therefore locally available to mitochondria for aerobic work at high intensities.

Animals↗
PubMed1999

Understanding the limitation of O2 supply through comparative physiology.

Comparative physiology and morphometry are used to explore the role of the lung in the limitation of oxygen supply to working muscle as it is experienced at aerobic capacity and in hypoxia such as at high altitude or in subterraneous burrows. In the human lung, as in that of most mammals, the pulmonary diffusing capacity is about 1.5 times larger than what is needed at aerobic capacity. In athletic species (horse, dog) there is no such excess diffusing capacity. As an exception the pronghorn antelope from the Rocky Mountains is a high performance athletic mammal whose lung shows an excess diffusing capacity. This is interpreted as a means to develop hypoxia tolerance as this animal performs its vigorous runs at high altitude. Information on the fossorial mole rat demonstrates that the lung's diffusing capacity is important in developing hypoxia tolerance. It is concluded that the lung is designed in relation to both internal and external constraints.

Aerobiosis↗
PubMed1999

Compensatory alveolar growth normalizes gas-exchange function in immature dogs after pneumonectomy.

To determine the extent and sources of adaptive response in gas-exchange to major lung resection during somatic maturation, immature male foxhounds underwent right pneumonectomy (R-Pnx, n = 5) or right thoracotomy without pneumonectomy (Sham, n = 6) at 2 mo of age. One year after surgery, exercise capacity and pulmonary gas-exchange were determined during treadmill exercise. Lung diffusing capacity (DL) and cardiac output were measured by a rebreathing technique. In animals after R-Pnx, maximal O2 uptake, lung volume, arterial blood gases, and DL during exercise were completely normal. Postmortem morphometric analysis 18 mo after R-Pnx (n = 3) showed a vigorous compensatory increase in alveolar septal tissue volume involving all cellular compartments of the septum compared with the control lung; as a result, alveolar-capillary surface areas and DL estimated by morphometry were restored to normal. In both groups, estimates of DL by the morphometric method agreed closely with estimates obtained by the physiological method during peak exercise. These data show that extensive lung resection in immature dogs stimulates a vigorous compensatory growth of alveolar tissue in excess of maturational lung growth, resulting in complete normalization of aerobic capacity and gas-exchange function at maturity.

Animals↗
PubMed1999

Gas exchange: large surface and thin barrier determine pulmonary diffusing capacity.

The lung is characterized by its diffusing capacity for oxygen, DLO2, which is estimated from morphometric information as a theoretical capacity. It is determined by the large gas exchange surface, the thin tissue barrier, and the amount of capillary blood. The question is asked whether DLO2 could be a limiting factor for O2 uptake in heavy exercise, particularly in athletes with their 50% higher O2 demand. This is answered by studying the relation between DLO2 and maximal O2 consumption in different sedentary and athletic mammals, comparing horse and cow, dog and goat, and, finally, the most athletic mammal, the pronghorn antelope of the Rocky Mountains. It is concluded that in athletic species the lung is just sufficient to satisfy the O2 needs and can therefore be a limiting factor for aerobic work.

Animals↗
PubMed1998

Limits for oxygen and substrate transport in mammals.

Environmental oxygen is transported by the respiratory cascade to the site of oxidation in active tissues. Under conditions of heavy exercise, it is ultimately the working skeletal muscle cells that set the aerobic demand because over 90 % of energy is spent in muscle cells. The pathways for oxygen and substrates converge in muscle mitochondria. In mammals, a structural limitation of carbohydrate and lipid transfer from the microvascular system to the muscle cells is reached at a moderate work intensity (i.e. at 40-50 % of VO2max). At higher work rates, intracellular substrate stores must be used for oxidation. Because of the importance of these intracellular stores for aerobic work, we find larger intramyocellular substrate stores in 'athletic' species as well as in endurance-trained human athletes. The transfer limitations for carbohydrates and lipids at the level of the sarcolemma imply that the design of the respiratory cascade from lungs to muscle mitochondria reflects primarily oxygen demand. Comparative studies indicate that the oxidative capacity of skeletal muscle tissue, and hence maximal oxygen demand, is adjusted by varying mitochondrial content. At the level of microcirculatory oxygen supply, it is found that muscle tissue capillarity is adjusted to muscle oxygen demand but that the capillary erythrocyte volume also plays a role. Oxygen delivery by the heart has long been recognized to be a key link in the oxygen transport chain. In allometric variation it is heart rate and in adaptive variation it is essentially stroke volume, and hence heart size, that determines maximal cardiac output. Again, haematocrit is an important variable that allows the heart of athletic species to generate higher flux rates for oxygen. The pulmonary gas exchanger offers only a negligible resistance to oxygen flux to the periphery. However, in contrast to all other steps in the respiratory cascade, the lungs have only a minimal phenotypical plasticity and appear, therefore, to be built with considerable structural redundancy in all but the most athletic species. Because of the lack of malleability, the lungs may ultimately become limiting for VO2max when adaptive processes have maximized O2 flux through the malleable downstream elements of the respiratory system: the heart, microcirculation and muscle mitochondria.

Animals↗
PubMed1997

Working underground: respiratory adaptations in the blind mole rat.

Mole rats (Spalax ehrenbergi superspecies) perform the heavy work of digging their subterranean burrows in Israel under highly hypoxic/hypercapnic conditions. Unlike most other mammals, they can achieve high levels of metabolic rate under these conditions, while their metabolic rate at low work rates is depressed. We explored, by comparing mole rats with white rats, whether and how this is related to adaptations in the design of the respiratory system, which determines the transfer of O2 from the lung to muscle mitochondria. At the same body mass, mole rats were found to have a significantly smaller total skeletal muscle mass than ordinary white rats (-22%). In contrast, the fractional volume of muscle mitochondria was larger by 46%. As a consequence, both species had the same total amount of mitochondria and achieved, under normoxia, the same V(O2max). Whereas the O2 transport capacity of the blood was not different, we found a larger capillary density (+31%) in the mole rat muscle, resulting in a reduced diffusion distance to mitochondria. The structural pulmonary diffusing capacity for O2 was greater in the mole rat (+44%), thus facilitating O2 uptake in hypoxia. We conclude that structural adaptations in lung and muscle tissue improve O2 diffusion conditions and serve to maintain high metabolic rates in hypoxia but have no consequences for achieving V(O2max) under normoxic conditions.

Adaptation, Physiological↗
PubMed1997

Effects of long-term hypergravity on muscle, heart and lung structure of mice.

Quantitative changes in lung, heart and muscle structure were assessed in mice exposed for 14 weeks to a gravitational field of 3 G since the age of 4 weeks; matched controls were kept at normal gravity (1 G). The body mass of 3-G-exposed mice was significantly reduced by 9%, while total skeletal muscle mass remained the same fraction of body mass. The mass of the soleus muscle was found to be significantly larger in 3-G-exposed mice both in absolute (+27%) and body mass specific terms (+42%). Capillary density was significantly reduced by 22% because of a relatively larger increase of fiber cross-sectional area (+47%) than of capillary to fiber ratio (+16%). Other morphometric variables remained unchanged with hypergravity. Heart mass and mitochondrial volume were both larger in 3-G-exposed mice (+15% and +27%, respectively). This difference reached statistical significance when normalized to body mass. The only significant difference in lung structure detectable by morphometric methods were a smaller volume (-9%), that paralleled lower body mass, and thinner alveolar septa (-12%). From these results it is concluded that the lung's support structures in mice are sufficiently strong to withstand the stress of long-term hypergravity; however, 3-G exposure leads to a selective hypertrophy of soleus muscle fibers while absolute capillary length in this muscle remains unaltered.

Adaptation, Physiological↗
PubMed1996

Development of the human fetal airway tree: analysis of the numerical density of airway endtips.

BACKGROUND: It has been long agreed that the lung contained, at the end of the pseudoglandular stage, mostly the future conductive airway tree and that the intra-acinar structures developed during the subsequent canalicular stage. Recent immunocytochemical investigations have disclosed that the epithelial cells lining the distal airways in the pseudoglandular stage have the characteristics of alveolar epithelial cells. The purpose of this study was to quantitatively evaluate the progress of fetal airway branching. METHODS: The numerical density of endtips of the airway tree was estimated in three human fetal right lungs after 3D reconstruction of airways from serial histologic sections. The CRLs of the three fetuses were 103 mm, 132 mm, and 145 mm. The former two corresponded to the late pseudoglandular stage and the last to the early canalicular stage. Three-dimensional reconstructions were performed on two portions of the upper and lower lobes in each lung. The numbers of endtips of the airway tree contained in the reconstructed portions were counted an the numerical densities calculated. RESULTS: The numerical densities in the parenchyma of the three right lungs were 1.2 x 10(3)/mm3, 1.7 x 10(3)/mm3, and 2.4 x 10(3)/mm3, respectively. The estimated total numbers of endtips in the whole right lung were 0.85 x 10(6), 2.25 x 10(6), and 5.17 x 10(6), which were equal to 2(19.8), 2(21.2), and 2(22.3), respectively. CONCLUSIONS: Since this suggests that 20 generations of branching were completed, we concluded that the airway branching has already reached the level of the future alveolar ducts in the late pseudoglandular stage.

Fetus↗