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E R Weibel

Publications and source records attributed to E R Weibel.

At least 19 recordsLinked to original sources
PubMed1992

Variations in function and design: testing symmorphosis in the respiratory system.

We explore the question of whether and to what extent the large variation in energy requirements observed among mammals is related to variations in the design of the respiratory system, from the lung to the mitochondria in muscle cells. Resting metabolic rate is determined by body size (allometric variation). Maximal rates of O2 consumption (VO2 max) also vary in a regular manner with body size, but adaptive variation allows some species to achieve much higher values than others of the same body size. We, therefore, consider adaptive variation as modulation of structures and functions above those determined by allometric variation. A model is presented that separates functional and design parameters at four steps of the respiratory cascade: the pulmonary gas exchanger, heart and blood, microvasculature, and mitochondria. The variations observed in these parameters are analyzed with respect to those in energy demand and are discussed in relation to the hypothesis of symmorphosis. We conclude that the design of the internal steps of the respiratory system (mitochondria, capillaries, blood, and heart) is matched to functional demand, whereas the lung maintains a variable excess of morphometric diffusing capacity which may be related to the facts that the lung has limited malleability and that it forms the interface with the environment.

Animals↗
PubMed1992

O2 delivery at VO2max and oxidative capacity in muscles of standardbred horses.

The purpose of this study was to describe the relationships between 16 physiological, biochemical, and morphological variables presumed to relate to the oxidative capacity in quadriceps muscles or muscle parts in Standardbred horses. The variables included O2 delivery (blood flow) and mean capillary transit time (MTT) during treadmill locomotion at whole animal maximal O2 consumption (VO2max, 134 +/- 2 ml.min-1 x kg-1), capillary density and capillary-to-fiber ratio, myoglobin concentration, oxidative enzyme activities, glycolytic enzyme activities, fiber type populations, and fiber size. These components of muscle metabolic capacity were found to be interrelated to varying degrees using correlation matrix analysis, with lactate dehydrogenase activity showing the most significant correlations (n = 14) with other variables. Most of the "oxidative" variables occurred in the highest quantities in the deepest muscle of the group (vastus intermedius) and in the deepest parts of the other quadriceps muscles where the highest proportions of type I fibers were localized. The highest blood flow measured with microspheres in the muscle group during exercise was in vastus intermedius muscle (145 ml.min-1 x 100 g-1), and the lowest was in the superficial part of rectus femoris muscle (32 ml.min-1 x 100 g-1). Average muscle blood flow during exercise at whole animal VO2max was 116 ml.min-1 x 100 g-1. Because skeletal muscle comprised 43% of total body mass (453 +/- 34 kg), total muscle blood flow was estimated at 226 l/min, which was approximately 78% of total cardiac output (288 l/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The concept of symmorphosis: a testable hypothesis of structure-function relationship.

The hypothesis that, in biological organisms, structural design is matched to functional demand is difficult to test because it is largely based on anecdotal evidence suggesting economic design. The hypothesis of symmorphosis postulates a quantitative match of design and function parameters within a defined functional system; because of its stringency it is refutable and can, therefore, be subjected to empirical test, for example, by assessing whether the structures that support the pathway for oxygen from the lung to the consumer in muscle cells are quantitatively adjusted to the limit of functional performance of the respiratory system. The study of allometric and adaptive variation leads to the conclusion that the hypothesis of symmorphosis is acceptable for all internal compartments of the respiratory system (blood, heart, muscle capillaries, and mitochondria), whereas it must be refuted for the lung that forms the interface to the environment.

Adaptation, Physiological↗
PubMed1991

Fractal geometry: a design principle for living organisms.

Fractal geometry allows structures to be quantitatively characterized in geometric terms even if their form is not even or regular, because fractal geometry deals with the geometry of hierarchies and random processes. The hypothesis is explored that fractal geometry serves as a design principle in biological organisms. The internal membrane surface of cells, or the inner lung surface, are difficult to describe in terms of classical geometry, but they are found to show properties describable by fractal geometry, at least sectionwise and within certain bounds set by deterministic design properties. Concepts of fractal geometry are most useful in characterizing the structure of branching trees, such as those found in pulmonary airways and in blood vessels. This explains how the large internal gas exchange surface of the lung can be homogeneously and efficiently ventilated and perfused at low energetic cost. It is concluded that to consider fractal geometry as a biological design principle is heuristically most productive and provides insights into possibilities of efficient genetic programming of biological form.

Animals↗
PubMed1991

PET evaluation of pulmonary vascular permeability: a structure-function correlation.

We compared regional measurements of the pulmonary transcapillary escape rate (rPTCER) for 68Ga-transferrin, obtained by positron emission tomography (PET), with morphometric data obtained from corresponding tissue samples in six anesthetized mechanically ventilated dogs, 1 h after oleic acid administration to either the left caudal lobe (0.015 ml/kg; Lobar group, n = 3) or the right atrium (0.08 ml/kg; Diffuse group, n = 3). Data were obtained from 48 regions in both injured and control lobes (right caudal lobes from the Lobar group). The volume density of edematous or hemorrhagic alveoli at the light-microscopic level was directly related to rPTCER (r = 0.82 for regions with rPTCER values less than 700 x 10(-4) min-1). Likewise, the relative surface of abnormal capillary endothelium and alveolar epithelium at the electron-microscopic level correlated well with rPTCER (r = 0.87 for regions with rPTCER less than 1,200 X 10(-4) min-1). We conclude that the rPTCER measurements obtained with PET reflect the morphological heterogeneity present in oleic acid-damaged lung tissue. Thus rPTCER measurements should be useful as a noninvasive quantitative index of lung injury. Furthermore, the tomographic image display of rPTCER may allow PET to be used as a "physiological probe" to guide tissue excision for later histological evaluation when lung injury is heterogeneous.

Animals↗
PubMed1990

Recent stereological methods for cell biology: a brief survey.

With the advent of many new tools over the last five years, stereology has become simpler, assumption-free, and more efficient but, at the same time, new terms and concepts have proliferated, which risk overwhelming potential users. The present review is intended to meet the urgent need for a structured classification and evaluation of the newest stereological methods. Being fairly comprehensive, the exposition is necessarily succinct: the reader is referred to selected references for the necessary details and examples.

Animals↗
PubMed1989

High rate of O2 consumption in exercising foxes: large PO2 difference drives diffusion across the lung.

The fox has one of the highest mass specific rates of maximal oxygen consumption (VO2max/Mb) that has been measured, yet its specific pulmonary diffusing capacity (DLO2/Mb, measured morphometrically) is similar to that of most mammalian species. It achieves a high O2 flux per unit DLO2 with a large partial pressure difference driving O2 diffusion from alveolar gas to capillary blood (PAO2-PbO2). This paper explores the mechanisms that the fox utilizes to achieve this large pressure difference and the extent to which it exploits its structural diffusing capacity. Foxes were exercised on a treadmill at maximal rates of O2 uptake. The following parameters were measured or calculated: arterial and mixed venous PO2, PCO2, pH and O2 concentration of the blood, cardiac output, hemoglobin concentration and O2 equilibrium curve of the blood, and morphometric estimates of pulmonary capillary volume and pulmonary diffusing capacity for O2. These data were used to calculate pulmonary capillary transit time and the time course of the change in O2 concentration and PO2 of the blood as it transits the lung. The fox has a morphometric pulmonary diffusing capacity of 0.098 ml O2.sec-1.mm Hg-1.kg-1. At VO2 max (3.6 ml O2.sec-1.kg-1) the fox hyperventilates, resulting in a high PAO2 (124 mm Hg); it also maintains a low PbO2 (88 mm Hg) by having a short transit time (0.13 sec) due to a high specific cardiac output (25 ml.sec-1.kg-1). Our calculations indicate that at VO2max the fox uses almost all of the pulmonary capillary transit time for O2 equilibration, in contrast to other species.

Animals↗
PubMed1989

Oxidative capacity of muscle and mitochondria: correlation of physiological, biochemical, and morphometric characteristics.

The oxidative capacity of cat skeletal muscles (soleus, gracilis, and gracilis chronically stimulated for 28 days) was derived from the total mitochondrial content in the muscle, the surface area of mitochondrial inner membranes, and respiratory activities of isolated mitochondria. Mitochondrial content was estimated by standard morphometry. The surface area of mitochondrial inner membranes per unit volume of mitochondria was estimated by a stereological method. The respiratory activities of isolated mitochondria were measured biochemically, using pyruvate/malate, glutamate/malate, succinate, or cytochrome c as substrate. Structurally and functionally, mitochondria from the three muscle types showed nearly identical characteristics. Oxidative activity was dependent on substrate; with succinate, 5.8 ml of O2 per min per ml of mitochondria was the rate most likely to represent physiological conditions. Oxidative activities of 3.1 ml.min-1.ml-1 with pyruvate/malate and 14.5 ml.min-1.ml-1 with cytochrome c as substrates were theoretical lower and upper bounds. The oxidative capacity of each of the three muscles was thus in direct proportion to the total volume of mitochondria in the muscle. The respiratory capacity of isolated mitochondria was very near to the maximal oxygen uptake rate of mitochondria that is commonly estimated in intact muscles of a wide variety of animals.

Animals↗
PubMed1989

Measuring through the microscope: development and evolution of stereological methods.

Obtaining, by means of microscopy, meaningful measurements pertaining to spatial structures requires methods which allow three-dimensional quantitative information to be derived from the reduced information available on the two-dimensional flat sections of the structure. The most powerful methods to that effect are those of stereology which are based on mathematical principles. This paper reviews the early invention of these methods, which sought to solve practical problems, and their further evolution as more rigorous mathematical foundations were developed. It is demonstrated that stereological methods are essentially sampling methods and that newer trends provide new and sound solutions to old and elusive problems, such as anisotropy or particle number and size.

Humans↗
PubMed1989

Capillary and mitochondrial unit in muscles of a large lizard.

We asked whether capillaries and mitochondria form a structural and functional unit in the musculature of the Cuban iguana (Cyclura nubila) similar to that found in mammals. We found a significant correlation between capillary length density [Jv(c, f)] and mitochondrial volume density [Vv(mt, f)] of the musculature with a slope that revealed that on average 3.5 km of capillaries were associated with each milliliter of mitochondria (vs. approximately 11 km/ml in mammals). These capillaries had a diameter of 9 microns (vs. 4.5 microns in mammals), and the mitochondria had a surface density of the inner membranes of 25 m2/ml (vs. 30-45 m2/ml in mammals). These dimensions resulted in ratios of capillary to mitochondrial volume (0.22 ml/ml) and capillary wall to mitochondrial membrane surface area (39 cm2/m2) that were similar in Cyclura to those found in mammals (approximately 0.18 ml/ml and 35-52 cm2/m2, respectively). Also in agreement with mammalian values were the average oxidative capacity of the mitochondria derived from maximum rate of O2 consumption (VO2max) during exercise at 37 degrees C and the inner mitochondrial membrane surface area [S(im)] of the musculature [VO2max/S(im) = 0.04 vs. 0.06-0.15 ml O2.m-2.min-1 in mammals]. These common structural and functional relationships support the notion that capillaries and mitochondria represent a similar fundamental unit in muscles of both Cyclura and mammals.

Animals↗
PubMed1989

Capillary tortuosity in skeletal muscles of mammals depends on muscle contraction.

Capillary orientation (anisotropy) was compared in hindlimb muscles of mammals of different size and/or different aerobic capacity (dog, goat, pony, and calf). All muscles were fixed by vascular perfusion at sarcomere lengths ranging from 1.5 to 2.7 micron. The ratios of capillary counts per fiber cross-sectional area on two sets of sections (0 and 90 degrees) to the muscle fiber axis were used to estimate capillary anisotropy and the coefficient c(K,0) relating 1) capillary counts on transverse sections (a commonly used parameter to assess muscle capillarity) and 2) capillary length per volume of fiber (i.e., capillary length density). Capillary orientation parallel to the muscle fiber axis decreased substantially with muscle fiber shortening. In muscles fixed at sarcomere lengths of 2.69 microns (dog vastus intermedius) and 1.52 microns (dog gastrocnemius), capillary tortuosity and branching added 7 and 64%, respectively, to capillary length density. The data obtained in this study are highly consistent with the previously demonstrated relationship between capillary anisotropy and sarcomere length in extended vs. contracted rat muscles, by use of the same method. Capillary anisotropy in mammalian locomotory muscles is curvilinearly related to sarcomere length. No systematic difference was found in capillary tortuosity with either body size, athletic ability, or aerobic capacity. Capillary tortuosity is a consequence of fiber shortening rather than an indicator of the O2 requirements of the tissue.

Animals↗
PubMed1989

Oxygen transport during exercise in large mammals. II. Oxygen uptake by the pulmonary gas exchanger.

Because the maximal rate of O2 consumption (VO2max) of the horse is 2.6 times larger than that of steers of equal size, we wondered whether their pulmonary gas exchanger is proportionately larger. Three Standardbred racehorses [body mass (Mb) = 447 kg] and three domestic steers (Mb = 474 kg) whose cardiovascular function at VO2max had been thoroughly studied (Jones et al. J. Appl. Physiol. 67: 862-870, 1989) were used to study their lungs by morphometry. The basic morphometric parameters were similar in both species. The nearly 2 times larger lung volumes of the horses caused the gas exchange surfaces and capillary blood volume to be 1.6 to 1.8 times larger. Morphometric pulmonary diffusing capacity was 2 times larger in the horse than in the steer; the 2.6-fold greater rate of O2 uptake thus required the alveolar-capillary PO2 difference to be 1.3 times larger in the horse than in the steer. Combining physiological and morphometric data, we calculated capillary transit time at VO2max to be 0.4-0.5 s. Bohr integration showed capillary blood to be equilibrated with alveolar air after 75 and 58% of transit time in horses and steers, respectively; horses maintain a smaller degree of redundancy in their pulmonary gas exchanger.

Animals↗
PubMed1988

Morphometry of the human pulmonary acinus.

The geometry and morphometry of intraacinar airways in human lungs were studied on silicone rubber casts from two adult lungs. We defined acini as the complex of alveolated airways distal to the terminal bronchioles--that is, beginning with the first-order respiratory or transitional bronchiole. The morphological properties of pulmonary acini are described. The acinar volume averages 187 mm3 (SD +/- 79 mm3). Intraacinar airways branch dichotomously over about 9 generations (range 6-12). The internal airway diameter falls from 500 micron to 270 micron between acinar generations 0 and 10, whereas the outer diameter (including the sleeve of alveoli) remains constant at 700 micron. Towards the periphery the size of alveoli increases and clusters of alveoli become more numerous. The longitudinal path length of acinar airways (defined as the distance along the ducts from the transitional bronchiole to the alveolar sacs) averages 8.8 mm (+/- 1.4 mm). The morphometric data collected in this study are used to construct an idealized model of human acinar airways that can be related to existing models of the human bronchial tree.

Adult↗
PubMed1988

Mitochondrial size and shape in equine skeletal muscle: a three-dimensional reconstruction study.

Individual mitochondria were reconstructed from ultrathin serial sections of selected muscle fibers in the M. semitendinosus of a horse, over a length of nearly two sarcomeres. Mitochondria were found to be highly variable, with size and complexity of single mitochondria increasing with the fractional part of a fiber occupied by mitochondria. In fibers with a mitochondrial volume density of less than 4%, corresponding to the mitochondrial content of fast-twitch glycolytic fibers, mitochondria were generally rather simple cylindrical shapes, oriented parallel to the myofibrils. In fibers with a mitochondrial volume density of more than 7%, corresponding to the mitochondrial content of slow-oxidative or fast-oxidative glycolytic fibers, mitochondria were generally cylindrical at the A-band and Z-plate level of the muscle sarcomeres. However, these mitochondria often had transverse extensions or interconnections that occurred at the I-band level. Volumes of individual mitochondria ranged from as small as a few thousandths of a micron3 up to several micron3 for the incompletely reconstructed portions of the largest mitochondria. Mitochondrial profiles that one would classify from single sections as subsarcolemmal were found to interconnect with other profiles deeper within the fiber. This suggests that it is unlikely that subsarcolemmal and interfibrillar mitochondria are two structurally distinct populations. However, we found no evidence of a reticulum completely interlinking all mitochondrial material in a muscle fiber.

Animals↗
PubMed1988

Ultrastructural aspects of pulmonary edema.

The alveolar septa are designed for gas exchange as well as for the exchange of water and solutes. The organization of the tissue elements and the ultrastructural architecture of the alveolar septa minimize the interference between gas and liquid exchange even when excess water begins to accumulate in the septal interstices and the alveoli. Larger amounts of alveolar edema fluid, however, profoundly alter both function and structure of the lung parenchyma. As to the routes of abnormal fluid movement, the ultrastructural findings are not always conclusive, though in some types of permeability edema frank anatomic disruptions of the endothelial and epithelial barriers can be observed. On the other hand, in hemodynamic edema the permeability barriers appear to be intact. However, experiments involving macromolecular tracers and the presence of numerous red blood cells in the interstitial and alveolar spaces indicate that transient separations of cell junctions have taken place.

Acute Disease↗
PubMed1988

Evaluation of lung diffusing capacity by physiological and morphometric techniques.

Determinations of pulmonary diffusing capacity for CO (DLCO) by physiological and morphometric techniques have resulted in substantially different values for both DLCO and its major components. To evaluate the differences in these methods of measurement of DLCO, measurements were made under controlled conditions on isolated perfused dog lungs. Multiple gas-rebreathing techniques were used to measure DLCO, the membrane component of the diffusing capacity for CO (DmCO), and pulmonary capillary blood volume (Vc) in both anesthetized dogs and after isolation and perfusion of their lungs. The isolated perfused lungs were than perfusion fixed for morphometric analysis of the components of DLCO. The values obtained morphometrically for Vc were similar to those measured by physiological techniques. Perfusion fixation did not substantially alter the morphometric estimate of DmCO when compared with previous values obtained on inflation fixed lungs. However, the morphometric estimate of DmCO was over 10 times higher than that estimated physiologically. Analysis of the potential errors in the techniques suggests that the correct value for DmCO is substantially higher than that commonly estimated by use of physiological techniques and that the explanation for the difference is due to a number of factors that can influence the binding of CO to hemoglobin under in vivo conditions. The net effect of these factors can be represented by an unknown in each component of the Roughton-Forster relationship so that 1/DL = 1/(U1.Dm) + 1/(U2.theta Vc), where theta is the binding rate for CO to hemoglobin. Because the magnitudes of the unknown terms (U1 and U2) in the Roughton-Forster relationship are likely to be large, this relationship cannot be reliably used to determine Dm and Vc.

Animals↗
PubMed1988

Variability of fiber size, capillary density and capillary length related to horse muscle fixation procedures.

Muscle samples were taken from the superficial part of the semitendinosus muscle of four standardbred horses to compare the effects of three different fixation procedures on fiber size and capillarity. Infiltration fixation in an extended position of the muscle was compared to immersion fixation and infiltration fixation in a flexed position of the limb. The capillary length density was used to estimate muscle capillarity. Infiltration fixation was found to be a viable alternative to perfusion fixation of muscles for morphometry of fiber size and capillary length density allowing muscle tissue fixation at a defined sarcomere length without fiber kinking.

Animals↗